0a · The Five Rules

But reorder it - slot Proof firmly in the middle - and the whole framework transforms. What was a cautionary tale about bad strategy becomes a practical, honest philosophy for how pharmaceutical development should work. Premise. Proof. Promise. This is the sequence I’ve come to believe in after years watching (and occasionally helping) programmes succeed or stumble. It’s not flashy, but it’s robust, it respects the science, and it gives genuine innovation a fighting chance. Importantly it also leaves the messaging of the Proof until you genuinely know it is a promise rather than a hope - and promises something that a) you know you can deliver and b) that you know your audience wants/ values.

Start with a strong Premise

Everything worthwhile begins with the idea. Not the generic “there’s an unmet need in oncology/cardio/metabolic” slide that appears in every deck, but a sharp, hypothesis-driven premise about what this specific molecule might achieve in the real world.

Why this target? Why this modality at this moment in biological understanding? What precise patient experience or disease dynamic are we aiming to shift, and why do we believe our approach will succeed where others have fallen short?

A strong premise is falsifiable, ambitious yet grounded, and carries a genuine point of view. It draws on deep biology or clinical observation but adds that spark of asymmetric insight - the kind I’ve written about before. Choose the right premise and you create an immediate asymmetric learning advantage: every subsequent experiment, trial, and regulatory interaction becomes an opportunity to pull ahead while competitors are still splashing around in the same data pond.

This is where the metronome of innovation starts ticking properly. Rush or dilute the premise and you’re condemned to incrementalism from day one. Nail it and you’ve set the tempo for everything that follows.

Then build rigorous Proof

Only once the premise is locked down do you commit fully to generating proof that it actually holds water. And by proof I don’t mean the comforting slides that R&D and commercial teams love. I mean mechanistic understanding, translational data, and well-designed clinical evidence that the molecule does what you hoped - in the patients who matter.

This is the stage where most organisations lose their way. Commercial pressure leads them to write an optimistic Promise first, then scramble backwards to manufacture supporting data. The predictable consequences: late-stage surprises, label negotiations that strip away the headline claims, and post-approval commitments that quietly confess the original hype was ahead of the evidence.

When you protect the Proof phase, magic happens. You generate real optionality. You discover not just whether the drug “works,” but where it works best, in whom, and with what trade-offs. You can pivot intelligently, kill early when needed, or double down with conviction. Trial design stays scientific rather than defensive. Regulatory conversations become demonstrations of truth rather than exercises in persuasion.

This aligns closely with the asymmetric learning philosophy I’ve explored: the companies that win aren’t necessarily the ones with the biggest budgets or the loudest voice - they’re the ones that learn faster and more honestly about their molecule’s true nature.

Only then make the Promise

The Promise belongs at the end. Not as a clever slogan dreamed up. (or pieced together) in a workshop, but as a clear, evidence-backed commitment to regulators, payers, physicians, and - most importantly - patients.

“This molecule, grounded in this premise and proven through this body of evidence, delivers these specific clinical benefits, with this safety profile, generating this level of economic and humanistic value for these well-defined patients.”

Because the Promise flows directly from the Premise and the Proof, it feels earned rather than aspirational. Positioning finally earns its seat at the table - no longer papering over scientific gaps, but translating hard-won truth into language the market can understand, trust, and act upon.

Why this order matters - illustrated by real programmes

Run the sequence backwards (or start with the Promise) and the pattern is depressingly familiar: beautiful early decks, wobbly Phase 3 readouts, products that reach the market with modest differentiation and even more modest pricing power.

Contrast that with programmes that - whether consciously or by good fortune - followed something closer to Premise → Proof → Promise.

The GLP-1 receptor agonists are a textbook case. The foundational premise emerged from decades of incretin biology - understanding how these hormones regulate not just glucose but energy balance, appetite, and cardiovascular health. Rigorous prooffollowed: mechanistic studies, then clinical programmes that started in type 2 diabetes and expanded thoughtfully into obesity and cardiovascular outcomes. Only with that foundation did the powerful promise crystallise - substantial, durable weight loss and risk reduction that payers and patients could embrace as genuine value.

Pembrolizumab (Keytruda) followed a similar path. The premise was rooted in deep immunology: PD-1 blockade could unleash the immune system against tumours in ways that cut across traditional cancer classifications. Targeted proof in biomarker-defined populations (MSI-high, high TMB) came first. The resulting promise - including the landmark tumour-agnostic approval - felt biologically credible and has genuinely shifted treatment paradigms.

You see echoes of this disciplined sequence in other differentiated medicines that didn’t merely hit an endpoint but changed how clinicians think about a disease. They succeeded because the Promise was the conclusion of serious work, not the starting gun.

Practical implications for how we work

Adopting Premise → Proof → Promise as your guiding philosophy changes behaviours across the organisation:

• Portfolio decisions become premise-led first, with financial modelling as a supporting voice rather than the loudest one.

• Clinical development teams design trials around the scientific question, not the hoped-for label.

• Regulatory strategy focuses on demonstrating the premise with integrity, reducing the need for last-minute rescue negotiations.

• Early commercial and medical affairs involvement shifts from “what can we claim?” to the far more useful question: “what proof do we genuinely need, and how do we generate it efficiently?”

It also creates space for the kind of honest kill decisions that protect capital and reputation. In an industry that talks constantly about innovation but often delivers incremental me-too products, this sequence is one practical way to tilt the odds back toward meaningful progress.

Final thought

Pharmaceutical development is not marketing with some science attached. It is a scientific and medical endeavour whose commercial success should be the natural outcome of doing the hard parts properly.

The industry loves to celebrate disruption and breakthrough thinking. Fine. Here’s one concrete way to move beyond the slogans: start with a strong, asymmetric Premise, generate rigorous Proof that honours the biology, and only then articulate a Promise you can actually stand behind.

Get this sequence right and you don’t just launch products - you build durable competitive advantage and, more importantly, deliver medicines that genuinely matter.

But they shouldn’t.

Positioning always serves the same purpose: turning a molecule into a differentiated, ownable medicine that shapes its category rather than commoditising inside it. It always heads for the same destination: a crisp, ownable idea of what this product will become. What changes by phase is the deliverable - the tangible output that advances you toward that unchanging North Star.

This is the practical expression of everything we’ve been exploring on this Substack: Deep Positioning in the fog of Phase I, pre-positioning as the grammatical roots, the idea as the true North Star, unmet needs as malleable, and active (wildflower) versus passive (scatter) approaches. The discipline is consistent. The vehicle adapts to the terrain.

Same Destination, Different Deliverables

The molecule doesn’t change. The regulatory pathway doesn’t fundamentally change. But your strategic output must evolve - or you default to symmetry and average outcomes. Deep Positioning protects the substance while adapting the form.

The unchanging North Star (“this product will become…”) is the key insight. Most teams chase data first, then retrofit a story. By the time late-stage teams receive the creative brief, optionality has evaporated - indications narrowed, endpoints locked, subpopulations ignored, and the label shaped by statistical significance rather than strategic differentiation. This approach flips the sequence: commercial insight informs R&D choices early (without “telling them what to do”), evidence generation serves the idea in mid-stage, and launch execution feels inevitable because the soil was prepared.

This aligns with how true category creators work.

Setting Destination (Early Phases)

This is pre-positioning in action. You are placing the molecule in relation to a future market that doesn’t fully exist yet.

High uncertainty is an asset. Start with the idea - that simple, evocative mental model of what the product will become. Write “…will become” at the top of every briefing document. Play with multiple candidate ideas and multiple target product profiles (TPPs) while flexibility is highest. Explore the mechanism of effect (what the patient and physician actually experience) rather than getting lost in the mechanism of action. The living “North Star document” becomes practical gold - forcing alignment across clinical, regulatory, and commercial teams without bureaucracy. Biomarker or subpopulation bets made here are what create defensible moats.

Practical outputs:

• A living “North Star document” that clinical, regulatory, and commercial teams reference for every major decision.

• Early choices on indication focus, sub-populations, biomarkers, dose-ranging strategy, and evidence-generation priorities.

• Optionality preserved (or deliberately created) so you don’t bake in commoditisation before the fog lifts.

Example: Ocrevus (ocrelizumab). Early Deep Positioning framed it as the first therapy to meaningfully target B cells as a central driver of MS pathology - not just in relapsing forms, but across the spectrum, including primary progressive disease. The North Star idea was bold: “Ocrevus will become the high-efficacy treatment that redefines disease modification in MS by slowing disability progression even where nothing had worked before.” This guided early investment in PPMS trials alongside RMS, B-cell biomarker exploration, and evidence strategies focused on the patient experience of reduced progression rather than just relapse reduction.

This is not “commercial telling R&D what to do.” It is integrated Deep Positioning: using commercial insight to shape what product actually gets finished. Do this well, and symmetry traps become avoidable. Do it late, and defaults harden.

Framing the Label (Mid-Development)

Here, the work shifts from exploration to hardening. You are building the defensible path that gets you there in the eyes of regulators and payers.

This is where many good ideas die quietly. The deliverable is an evidence package explicitly designed to support the idea:

• Trial endpoints and patient populations chosen to make the differentiated effect credible and ownable.

• Statistical and clinical relevance aligned with the value story (not just “non-inferior + a bit better on one measure”).

• Label language and claims strategy pressure-tested against the North Star.

Endpoints chosen purely for “clean statistics” instead of ownable clinical experience produce labels that say “works like the others, maybe a bit better on X.” Framing the label is still Deep Positioning — it is translating the destination into regulatory and payer reality.

Ocrevus continued: The OPERA and ORATORIO trials were deliberately designed around endpoints that highlighted impact on disability progression in a population with no prior approved options. This produced label language that reinforced rather than diluted the North Star.

Communicating (Pre-Launch and Beyond)

Only now does external storytelling take centre stage - but it is never invention. It is the final expression (and amplification) of the Deep Position you have been building since the earliest phases.

If the prior stages were done right, this isn’t creation from scratch - it is amplification. Market shaping (turning latent wants into recognised needs) works because KOLs, payers, and physicians have been subtly primed.

Deliverables here include:

• Consistent messaging frameworks, sales materials, payer dossiers, KOL engagement, and publication plans - all orbiting the same idea.

• Active market shaping: redefining standards of care so the label lands as the obvious choice.

The wildflower analogy is powerful here. Passive approaches scatter data on an unprepared market and hope for colour. Active (Deep) Positioning prepared the soil from Phase I. The communication feels inevitable.

Ocrevus in market: By launch, the ground was ready. Positioning emphasised early high-efficacy use and its unique PPMS approval. Ocrevus rapidly became the most prescribed MS DMT globally, redefining expectations.

Practical Extensions and Caveats

To make this real:

• Quantify optionality early: For each candidate idea/TPP, map “symmetry risk” - what happens if competitors advance similarly? Which paths create genuine asymmetric upside?

• Give the North Star document teeth: Tie it to milestone gates so it doesn’t become shelfware.

• Anticipate real-world friction: Regulatory conservatism and payer pressures can force dilution. Strong Deep Positioning doesn’t eliminate trade-offs, but it gives you clearer data (“If we drop this subpopulation, we lose X differentiation but gain Y probability of approval”).

• Measure crispness: Test the IDEA internally first (does every team member describe the product the same way unprompted?) and then with small external panels.

The Discipline That Doesn’t Change

The beauty - and the rigour - of this approach is that the destination never moves. You simply adapt the vehicle to each phase’s terrain:

• Early: high flexibility, low data → set direction with the IDEA.

• Mid: rising data, regulatory constraints → harden evidence around the IDEA.

• Late: full data, market visibility → shape and communicate the IDEA at scale.

Companies that treat positioning as a constant strategic thread (rather than a late-stage tactical exercise) don’t just launch better. They create medicines that define categories.If you’re living this right now in your pipeline — wrestling with early destination-setting, label-framing trade-offs, or market-shaping execution — I’d love your thoughts or war stories. Reply here or email me. The more real examples we gather, the stronger Version 2 of Pharmaceutical Positioning becomes.

But what if the real differentiator isn’t sharper tactics or flawless operational delivery? What if it is the quality of the strategy itself?

This is the heart of true launch excellence: building an excellent strategy - one that is bold, differentiated, patient-centred, and grounded in deep insight—and then executing it with discipline and agility. In practice, an excellent strategy executed with greatness consistently outperforms a merely great (or solid) strategy executed perfectly.

What “Launch Excellence” Really Means in Pharma

Launch excellence is not a buzzword for slick campaigns or on-time deliverables. It is the disciplined alignment of a high-quality commercial strategy with the organisational capability to bring it to life across global, regional, and local levels.

Core elements typically include:

• A sharply defined, insight-driven value proposition rooted in unmet needs, patient journeys, and evolving stakeholder priorities.

• Clear indication sequencing, positioning, and competitive differentiation.

• Integrated evidence, market access, and medical strategies that support the commercial ambition.

• Cross-functional alignment and organisational readiness.

• Mechanisms for ongoing measurement and adaptive optimisation.

The critical insight from my years of launch analyses is that the ceiling on performance is largely set by the strategy. A mediocre or “safe” strategy - well-positioned but not truly differentiating - has a built-in performance cap, no matter how flawlessly the tactics are delivered. Communicating a vague notion of your product perfectly can only leave people with a vague idea of where it fits.

The Strategy-First Perspective

As Sun Tzu famously observed in The Art of War: “Strategy without tactics is the slowest route to victory. Tactics without strategy is the noise before defeat.”In pharmaceutical commercialisation, this ancient wisdom rings especially true. Strategy is where the hard choices are made: which patient segments to prioritise first, how to sequence indications, what value story will resonate with payers and physicians in a crowded market, and where to accept trade-offs.

An excellent strategy does several things exceptionally well:

• It identifies and owns a distinctive space in the treatment paradigm (biomarker-driven, paradigm-shifting, or addressing a genuine unmet need others have overlooked).

• It anticipates competitive responses, regulatory shifts, and payer evolution.

• It sets an ambitious but achievable aspiration that energises the organisation and guides resource allocation.

A merely great strategy might be sound, evidence-based, and internally consistent (probably with a high degree of buy-in) - but it often lacks that extra edge of differentiation or foresight. It plays in a contested space without reshaping the conversation.

Execution (the tactics) then becomes a simple multiplier. Great execution - agile, aligned, detail-oriented, and adaptive - amplifies the strengths of an excellent strategy. Perfect execution of a merely great strategy, by contrast, can deliver respectable results - but rarely the breakout performance that creates category leaders or multi-billion-dollar franchises.

Case study 1: Excellent strategy – Merck’s Keytruda (pembrolizumab) in immuno-oncology
Keytruda entered a competitive PD-1 space as a second-to-market product behind Bristol Myers Squibb’s Opdivo. Rather than competing head-on in broad populations, Merck pursued a bold, biomarker-driven approach. It focused initially on patients with high PD-L1 expression (a clear predictor of response), secured accelerated approval in melanoma ahead of its rival, and invested aggressively in a vast clinical programme (over 1,600 trials) to expand indications rapidly - eventually reaching dozens of tumour types and tumour-agnostic approvals (e.g., MSI-high). This precise positioning, combined with foresight on indication sequencing and tissue-agnostic potential, allowed Keytruda to own a differentiated narrative, reshape treatment paradigms, and become one of the best-selling drugs in history, far outpacing Opdivo in long-term sales despite starting later.

Case study 2: Merely great strategy with strong execution – Bristol Myers Squibb’s Opdivo (nivolumab)
Opdivo launched first in some markets with solid clinical data and broad initial positioning (no strict biomarker restriction in certain indications). Execution was strong: effective field force activity, medical education, and market access efforts followed standard high-quality playbooks. I’d also suggest it ‘won’ launch, being ahead for a crucial few years.

However, the strategy lacked the sharp differentiation and biomarker focus of its rival in key areas such as first-line lung cancer. When broader populations failed to show the expected benefit in later trials, momentum slowed. Despite excellent tactical delivery, Opdivo could not fully reshape the conversation or match Keytruda’s expansive trajectory, illustrating how a sound but less distinctive strategy caps upside even with polished execution.

Why does this hold?

• Markets reward differentiation more than operational polish. Physicians and payers have limited bandwidth; a compelling, ownable narrative cuts through noise where incremental improvements do not.

• Excellent strategy reduces execution risk by providing clear direction, prioritisation, and decision rights. Teams know what matters most and can adapt without losing the plot.

• In today’s environment - accelerated approvals, intense competition, pricing pressure, and complex stakeholder ecosystems - strategy sets the trajectory, and does so with enough of a runway to make a difference. Execution determines how closely you follow it.

Execution drift is a real danger: even the best strategy can erode if tactics, incentives, and behaviours slowly diverge from the original intent. But the root cause is often a strategy that was never sharp enough to maintain alignment in the first place.

Evidence from the Field

Look at launches that have redefined their spaces. Many succeeded not because every tactical element was executed without flaw, but because the underlying strategy was excellent: precise first-indication focus, biomarker-driven positioning, or a value story that reshaped how the disease is managed. Subsequent expansions and optimisations built on that strong foundation.

Case study 3: Excellent strategy – Novo Nordisk’s semaglutide (Ozempic/Wegovy) in diabetes and obesity
Semaglutide was launched first for type 2 diabetes as Ozempic with a strong but conventional positioning. The real strategic masterstroke came with the decision to pursue and heavily invest in the obesity indication (Wegovy), backed by compelling STEP trial data showing significant weight loss. Novo anticipated the paradigm shift in treating obesity as a chronic disease, built a patient-centred value story around cardiometabolic benefits, and sequenced indications while investing in supply and access infrastructure. This bold, foresight-driven approach created a new category leader, drove explosive growth, and turned semaglutide into a multi-billion-dollar franchise that redefined expectations for metabolic therapies - despite later supply challenges and competition.

Case study 4: Merely great strategy – A typical “me-better” oncology or immunology follow-on product
Many second- or third-in-class therapies in crowded fields (e.g., certain later PD-1/L1 inhibitors or JAK inhibitors) enter with robust phase 3 data, solid evidence packages, and well-resourced launches. Execution is often strong - comprehensive digital campaigns, key opinion leader engagement, and payer negotiations follow best-practice templates. Yet without a distinctive biomarker focus, unique patient segment ownership, or a narrative that truly reshapes the treatment paradigm, they achieve respectable but not category-leading uptake. First-year forecasts are frequently missed not due to poor tactics, but because the strategy failed to create meaningful separation in a payer-constrained, noise-filled market.

Conversely, products with solid science and merely competent positioning - cobbled together from team workshops and research decks - have often underperformed when the strategy failed to create meaningful separation from competitors, despite strong field force activity, digital campaigns, or market access efforts. Perfect delivery of incremental tactics rarely overcomes strategic shortcomings in crowded or payer-constrained markets.

Industry observations reinforce this: many launches miss near-launch forecasts not primarily because of poor tactical execution, but because the strategy underestimated competitive dynamics, misjudged value perception, or lacked the boldness needed to break through.

Building the Execution of Excellence

If strategy is the foundation, how do you operationalise this thinking?

1. Invest disproportionately in strategy quality. Spend the time (and external challenge) needed to pressure-test assumptions, explore scenarios, and refine differentiation. Ask: Does this strategy truly own a distinctive space, or is it “me-better” in a noisy field?

2. Design execution to serve the strategy. Remember: a great strategy might need a team to diverge from a template launch plan. Build alignment mechanisms, decision rights, and agility into the launch plan from day one. Focus resources on the few things that will move the strategic needle rather than trying to perfect every activity.

3. Accept “great” execution as sufficient when the strategy is excellent. Empower teams to adapt intelligently within clear guardrails. Speed and judgement often matter more than perfection in dynamic markets.

4. Measure strategic health, not just tactical KPIs. Track whether the core value narrative is landing, whether priority segments are responding, and whether the organisation remains aligned with the original strategic intent.

5. Treat launch capability as strategic. Institutionalise rigorous post-launch reviews focused on what the strategy got right or missed, so future strategies improve.

The Bottom Line

In pharmaceutical commercialisation, strategy sets the ceiling; execution determines how close you get to it.

Teams that master the execution of excellence start with an excellent strategy—bold, differentiated, and insight-led. They then execute it with greatness: disciplined, adaptive, and relentlessly focused on protecting and amplifying that strategic intent.

The result is launches that don’t just meet expectations but redefine what’s possible for patients and for the business.

Perfect execution is admirable. But as Sun Tzu reminds us, tactics without a superior strategy amount to noise before defeat. In an industry where one launch can shape a decade of performance, excellence begins - and largely ends - with strategy.

Picture two patches of ground in the same garden.

In the first, you simply scatter a handful of wildflower seeds straight onto the existing lawn. The grass is already thick, established, and competitive. The seeds land where they land. Some might germinate if they’re lucky enough to find a bare spot or a crack in the turf. Most won’t. The ones that do struggle – they’re smaller, less vibrant, easily overshadowed. You get a few pops of colour, but nothing transformative. That’s passive positioning.

In the second patch, you prepare the ground first. You clear the grass, turn the soil, add compost, create the right conditions for those seeds to take root deeply and flourish. You choose where each variety will thrive best – sun or shade, moist or dry. When the seeds go down, they don’t just survive; they explode into a meadow. That’s active positioning.

The difference isn’t in the quality of the seeds. It’s in whether you shape the environment before you plant.

This is exactly how pharmaceutical positioning works – or fails to work – in our industry.

Passive positioning is the default approach most companies still take. You develop the molecule through the traditional clinical gauntlet. You run the trials, generate the data, file the dossier. Then, at launch (or shortly before), you “position” by presenting the facts – mechanism of action, efficacy numbers, safety profile – and hope physicians, payers, and patients draw the right conclusions. You scatter the data onto an already crowded therapeutic “lawn” of established competitors, guidelines, and mental models. The product lands where it lands. It might get a few prescriptions if it’s marginally better on one endpoint. But it rarely transforms the landscape. It becomes commoditised, second-line, interchangeable. Passive positioning isn’t really positioning at all. It’s telling. It’s describing. And in today’s market, description is rarely enough.

Active positioning – what I’ve been calling Deep Positioning since the first book – starts much earlier. It treats the market itself as soil that can (and must) be prepared. From Phase I, sometimes even pre-clinical, you begin shaping the narrative, the unmet need, the stakeholder expectations, the evidence plan, the regulatory dialogue, and the commercial frame. You clear competing assumptions. You enrich the ground with the right “IDEA” (the true North Star we keep revisiting). You create the conditions where your molecule doesn’t just compete – it redefines the category.

Think about it:

• Passive: You reveal the Target Product Profile (TPP) early in market research and ask physicians to score it against existing options. They immediately stereotype the asset (“another MEK inhibitor,” “yet another anti-TNF”). The data becomes incremental by design.

• Active: You present the idea first – “Imagine a treatment that resets the disease clock in early Alzheimer’s” – before anyone sees the mechanism or the numbers. Imagination opens up. The positioning conversation becomes qualitative, not just quantitative. The product earns a unique mental space.

We’ve seen the consequences of passive positioning play out again and again: drugs that hit every endpoint but still struggle for uptake because the market was never prepared to receive them differently. Conversely, the active approach is what allows a handful of truly differentiated launches to reshape entire treatment paradigms – even when the molecule itself wasn’t dramatically superior on paper.

This is why pre-positioning (the grammatical roots we explored last month) matters so much. Pre-positioning is the invisible work of preparing the ground: placing the asset before the market forces, in relation to evolving patient needs, against outdated standards of care. It turns positioning from a late-stage marketing exercise into an integrated R&D-commercial discipline.

Unmet need, as we discussed in November, is not fixed. It’s fluid. Active positioning shapes what that need becomes. Passive positioning accepts whatever need already exists in the grass.

The choice is yours long before launch. Scatter and hope… or prepare and flourish.

I’m building Version 2 of Pharmaceutical Positioning right now in real time here on the Substack. If you’d like to be part of the conversation – share examples from your own pipeline, challenge the framework, or help refine it – just hit reply. The more voices we bring in, the richer the soil becomes.

Not this:

(The Luleå, Sweden server farm image here – massive, remote, arctic-chilled data halls)

You don’t picture rows of humming servers 70 miles from the Arctic Circle. Instead, you think of an invisible, reliable space where your photos, documents, and memories live - accessible anywhere, anytime. “The cloud” is an idea that simplifies staggering complexity into something intuitive and valuable. You don’t need to understand the engineering; you grasp what it’s for.

That, at its core, is positioning.

In pharmaceuticals, we often default to the technical reality, and the technical verbiage: mechanisms, endpoints, p-values. But the most powerful drugs aren’t defined by their biology alone - they’re defined by a crisp, ownable IDEA that guides development, communication, differentiation, and ultimately market success.

When the original version of this post appeared in 2022, I introduced the notion that every drug deserves an “IDEA” - a framing tool as simple and evocative as “the cloud.” Examples included:

• A statin as an “LDL lowerer” vs. an “anti-atherosclerotic”

• A JAK inhibitor as an “immune overactivity reducer,” “disease modifier,” or “hot joint cooler”

• An anti-angiogenic vs. a mere “VEGF inhibitor”

• A negative-symptoms schizophrenia agent as an “enabler of sociability” or “return-to-work therapy” rather than another generic “anti-schizophrenic”

These aren’t taglines. They’re mental models with edges - clear boundaries that make the drug’s value instantly graspable, even to non-experts.

Remember, the IDEA in IDEA Pharma is specific:

• Insight is core to iterating IDEAs: Insight-Differentiated attributes-Environment-Audience

Asymmetric Learning - Pharmaceutical Innovation

'Insight' seems to be the hardest word...

This is a piece from one of our training decks, because ‘insight’ is one of those words that is used a lot (overused), with little definition, and therefore little value in many conversations… However it isn’t going away, and is a fundamental part of positioning/ deep positioning, so we’d like to raise the general understanding in the industry…

Read more

2 years ago · 1 like · 1 comment · Mike Rea, SAI/ IDEA Pharma

Four years on, the Substack has explored how to make that idea not just conceptual, but strategic and proactive. Here’s the updated view.

1. The Best Time for the IDEA? Phase I (Rule #2)

The five real rules of pharmaceutical positioning (June 2025) distill it down:

The best time to position your drug was in Phase I. By the time data reads out, much of the framing is already locked in - endpoints chosen, comparators set, language habituated.

Start early. Play with multiple ideas via multiple target product profiles (TPPs). Ask: What if this is “the first nursing home avoider” in Alzheimer’s? Or “the sociability enabler” in schizophrenia? Each premise opens (or closes) development paths, communication strategies, and differentiation potential.

Write “...will become” at the top of every document (Rule #3). Your drug will become the standard for restoring independence in late-life cognition. That forward-looking language turns the idea into a North Star.

2. From Mechanism of Action to Mechanism of Effect

One of the biggest evolutions: distinguishing MoA (the lab truth) from MoE (the proximal, believable effect in the patient’s world).

A VEGF inhibitor is MoA. An “anti-angiogenic” is closer to MoE - it evokes starving tumors of blood supply. Even better: frame it as “the combo partner that finally makes anti-VEGF therapy work longer.”

In obesity, semaglutide’s MoA is GLP-1 agonism. Its winning MoE? “Dual-hormone synergy for sustainable weight reset” (as in Mounjaro’s framing). Proximal, meaningful, and stakeholder-resonant. Or, see our recent case study on Reblozyl, where the clients describe how the MoE changed everything in their market and marketplace.

The IDEA should prioritize MoE: what the patient/physician/payer experiences first, not the deepest biology. They want the effect, not the action.

3. Value Proposition > Vague Positioning

Value proposition really is better positioning (from the “5 years” series). Quantify the qualitative. Don’t stop at “LDL lowerer” - become “the vascular healer averting millions of CV events.” Not just symptom relief, but “the first step to independence” via meaningful gains in daily function.

Stories beat stats for belief (The Shortcut to Belief, 2025). Narrate the patient who returns to work, socializes again, or avoids institutionalization. These human outcomes make the IDEA stick.

4. Active Framing vs. Passive Description

Most positioning is passive: describe the data, hope it speaks. Active positioning presents the IDEA first - shape the lens before the evidence arrives.

Present “the immune overactivity reducer” before diving into JAK selectivity. Frame RSV as a preventable crisis (Arexvy’s success) before efficacy numbers. This is the shortcut to imagination and ownership.

5. Market Shaping: IDEAs Aren’t Fixed - They’re Malleable

Unmet need isn’t fixed (November 2025). It’s shaped. The POSITION model (October 2025) gives pharma/ biotech a pre-launch playbook: Prime stakeholders, Own the narrative, Shape standards, etc.

GSK didn’t wait for RSV vaccines to “prove” need - they shaped it into a public health imperative. Your idea can do the same: turn “wants” into recognized needs, create new standards, and capture disproportionate share.

6. The Idea of the IDEA: Fueling Deep Positioning from the Start

At IDEA, we’ve long championed the “IDEA” as the foundational spark for Deep Positioning - the crisp, ownable concept that not only simplifies a drug’s essence but actively shapes its trajectory from discovery onward. As detailed in “Deep Positioning: What, Why, When” and prototyped in our work, this early IDEA acts as a prototype engine, allowing teams to iterate multiple framings in Phase I to resolve market failures proactively. Its effect? By embedding the IDEA early, you influence everything from indication selection and endpoint design to stakeholder alignment, turning passive development into a market-shaping force. Take Eli Lilly’s Mounjaro: Its IDEA as “the dual GIP/GLP-1 that will become the obesity standard” didn’t just describe - it drove expansions in endpoints and narratives, reframing unmet needs as malleable “wants” and securing blockbuster status in a commoditized space. Without this early IDEA, positioning risks commoditization; with it, you unlock 3-5x greater value through strategic foresight.

In Closing: The IDEA as Your Mission

The notion of your potion isn’t a cute metaphor - it’s the origin point of value. Achieving simplicity is hard work. It forces early clarity on what the drug is truly for, who it serves, and why it matters more than alternatives.

In a world of IRA pressures, payer scrutiny, and commoditization risk, great ideas need great clients - teams willing to shape markets proactively.

Five years after launching this Substack, the journey continues - toward the second edition of the book, and toward more drugs that change lives because their ideas changed minds first.

Take GSK’s Arexvy, the RSV vaccine that captured 70% market share in its debut year, racking up $1.5 billion in sales despite a crowded field. Its edge? Pre-launch positioning that didn’t just highlight the clinical gap in older adult protection but framed it as an urgent, preventable crisis with seamless integration into primary care workflows. I bet you’ve heard about RSV recently? That’s not an accident, or an ‘ask’ by the medical community.

This isn’t luck; it’s strategic positioning at work - creating an ideal landing pod for the right craft. Traditional launches chase static needs, like superior ‘efficacy’ in oncology (remember, there’s no such thing as ‘efficacy’). But in 2025’s post-IRA landscape, where payers ration every dollar and physicians juggle burnout with evidence overload, success pivots on repositioning “wants” - subjective desires for convenience, support, and alignment that drive 40% of physicians’ brand preferences beyond pure clinical data. Needs are the objective baseline: a therapy that extends progression-free survival. Wants? The once-monthly infusion that frees up a clinic’s schedule, or the real-world evidence package that sways a formulary committee.

I wanted to unpack the want-vs.-need dichotomy, explore pre-launch tactics to position physicians’ and payers’ preferences, and dissect real-world wins.

I suspect, for this blog, the question isn’t if you can reposition the market - it’s how to do it before competitors even notice the gap.

Want vs. Need: The Positioning Pivot in Pharma Decision-Making

Picture a hematologist facing a relapsed multiple myeloma patient. The “need” is clear: a regimen with better durability than standards. But the “want”? A therapy positioned as minimizing site-of-care disruptions, backed by peer-validated data, and bundled with patient navigation tools to boost adherence.

Ignore the wants, and even gold-standard efficacy underwhelms - 50% of launches underperform due to experiential mismatches, not trial failures. Needs are data anchors: endpoints from Phase 3 proving safety and superiority. Wants are behavioral magnets: preferences honed by workflow realities, economic pressures, and ecosystem enablers. As (even) Deloitte’s 2025 commercial outlook notes, biopharma must “reimagine engagement” in an agile, tech-infused era where stakeholder perceptions shift quarterly. (I say ‘even’ because Deloitte markets like an accountant…) Unmet need feels etched in stone in regulatory filings, but it’s malleable - repositioned by real-world evidence, stakeholder dialogues, and narrative reframing. Regulators are human too, influenced by stories, and constructs, without realising that they are.

In low-unmet-need arenas like generics-saturated hypertension, pharma amplifies wants through targeted education, effectively “creating” perceived gaps via sharp positioning. Patients underscore this: Recent surveys show only about half feel pharma truly addresses their holistic needs, with affordability and access tipping loyalty scales. As Philip Kotler put it: “Marketing is the science of satisfying needs and wants through an exchange process.” But in 2025, with AI-driven personalization and RWE exploding, the exchange starts pre-launch - and deep positioning is the lever.

To visualize the pivot:

This framework isn’t abstract; it’s a positioning blueprint that turns fluid perceptions into launch velocity.

Positioning Physicians’ Wants: From Skeptics to Advocates

Physicians aren’t passive recipients of data - they’re time-strapped decision-makers whose brand appetite comes from non-clinical enablers like robust support and simplicity. Pre-launch is the window to reposition skepticism into advocacy, co-crafting narratives that make your asset indispensable. Even in the ZS (who tend not to grasp the idea of positioning at all) 2024 trends report, they emphasize that in a fragmented ecosystem, early experiential hooks outpace late-stage blitzes.

Tactics to Deploy 18–24 Months Out:

• KOL/HCP Co-Creation: Launch advisory boards and VR simulations to mine pain points, evolving your story collaboratively. This boosts advocacy by 20–30%, as HCPs become co-authors on publications on subgroup unmet needs. Track via Net Promoter Scores - top launches engage 2x more providers pre-approval.

• Educational Momentum: Deploy webinars, CMEs, and whitepapers reframing paradigms: “Your toolkit misses X% of high-risk cases - evolve with us.” Digital personalization via AI nudges fosters pre-launch excitement, per IQVIA’s 2025 playbook.

• Experience Differentiation: Prioritize wants like ease of dosing. Bayer’s Xarelto nailed this with ‘once-daily convenience’, seizing 50% share post-launch despite equivalent efficacy. Pair with apps for adherence tracking to reduce admin loads.

• Feedback Micro-Loops: Assemble cross-functional “battle teams” for iterative HCP input, honing messaging to fuse needs with wants.

A quick takeaway from recent polls: 70% of physicians prioritize medical information at diagnosis but won’t ignore peer networks for validation - lean into hybrid forums to bridge that gap. In the shadow of their reported burnout, these touches don’t just inform; they empower - and position your brand as the thoughtful partner.

Influencing Payers’ Wants: Securing Access Before Day One

Payers greenlight just 30% of new drugs in Year 1, denying over 70% for chronic conditions amid IRA squeezes - pre-launch positioning is a counterpunch, proving value that fits their playbook. Shift from “add-on risk” to “portfolio essential” by tailoring economics early.

Proven Plays, 6–18 Months Pre-Approval:

• Data Exchanges Under Cures Act: Share MOAs, trials, and budget models proactively. Highlight hospitalization reductions for ROI alignment - Simon-Kucher’s 2025 trends flag RWE as a payer “want” for JCA compliance.

• Segmented Value Stories: Customize for PBMs vs. plans: “Ditch legacy spend on X for Y outcomes.” HEOR dossiers justify premiums in oncology, per TJPA’s access pillars.

• Archetype Targeting: In rare diseases, educate on burden via patient voices; in generics fields, pitch off-label prevention. Engage via ICER forums to influence guidelines.

• Outcome-Based Contracts: Tie rebates to real metrics, quelling accountability fears in an IRA world.

Early engagement lifts formulary odds by 25%, per 2025 access reports - a real metric for success. As one payer exec quipped: “We want ‘spend on X buys Y’ - deliver it pre-filing.”

Case Studies: Proof in the Pipeline

Theory shines in practice. Here’s how deep positioning turned needs into wants:

• Celgene’s Revlimid: A “drumbeat” of pre-launch evidence - twice as much as rivals’ studies - kept hematologists involved with evolving data, sustaining myeloma dominance despite generics looming.

• 2018 Migraine Disruptor (Aimovig): Unbranded DTC via advocacy coalitions and PR built patient demand, reframing under-diagnosis as an “evolving crisis” - scripts surged 30% at launch, influencing HCPs and payers alike.

• Rare Disease Reimbursement Win: Early payer “burden-of-illness” dialogues with patient input secured rapid access, transforming niche needs into budgeted wants via frameworks like PPEF.

These aren’t outliers - first-to-market loses if the wants lag.

The Positioning Playbook: Act on Fluid Needs Now

Unmet need isn’t destiny - it’s the dough you knead into wants via KOL co-creation for HCPs and HEOR tales for payers. In 2025’s competitive landscape, pre-launch positioning isn’t a nice-to-have; it’s your moat - aligning seamlessly with the deep positioning principles we’re unpacking here.

Expanding on the Five Rules of Pharmaceutical Positioning: A Deeper Dive for Strategic Minds

In the ever-evolving arena of pharmaceutical launches, where unmet needs morph into shaped wants and clinical data battles payer scrutiny, my Five Rules of Pharmaceutical Positioning are a guide for those crafting not just products, but market shifts. As outlined in the Substack post, these rules distill the essence of “Deep Positioning” - a proactive, product-centric approach that embeds differentiation from the lab bench to the formulary.

While the original framework captures the high-level imperatives, let’s expand on each rule here, weaving in practical implications, real-world pharma examples and my own case studies, and ties to today’s post-IRA pressures. This isn’t theory; it’s a playbook for turning fluid perceptions into fortified market strongholds.

Drawing from my nine principles in Pharmaceutical Positioning, these five rules emphasize early, intentional action. Deep positioning challenges the inertia of “the obvious path” in R&D, urging teams to position not as an afterthought, but as the North Star guiding every decision. Let’s look, rule by rule.

Rule 1: Deep Positioning is About the Product

At its core, this rule flips the script on superficial brand-building. Traditional positioning - glossy ads etching a “lifestyle” image into HCP minds - treats the drug as a canvas for marketing flair. Deep Positioning is more surgical: a relentless focus on the molecule’s intrinsic and extrinsic architecture: indication selection, dosing regimens, formulation tweaks, endpoint choices, and the value proposition forged in Phase I/II. The drug’s DNA doesn’t change post-discovery; what evolves is how you sculpt it into a differentiated contender.

Expansion and Application: In a world where 70% of launches underperform due to commoditized perceptions, this rule demands baking in “unmet need evolution” from day one. Consider Novartis’ Entresto in heart failure: Early decisions to prioritize sacubitril/valsartan’s unique dual mechanism (neprilysin inhibition + ARB) over generic ARBs created a product inherently positioned as a “paradigm shift,” not just another add-on. (I know, because Entresto was regarded as a prerequisite in my regimen, even in the UK’s NHS…)

This wasn’t marketing spin; it was endpoint design yielding ARNI superiority data that payers couldn’t ignore, driving $5B+ peak sales. I worked on Entresto, repositioning it in the US, after an underwhelming launch - we focused on talking to payers, and that traction from the development programme took off…

For your pipeline: Audit early development milestones. Ask: Does this formulation address a “want,” such as oral over IV, for community settings? Tie it to Rule 3’s future vision - position the product to become the convenience king, evidenced by adherence studies in the trials. In low-unmet-need spaces like hypertension/ heart failure, this granular focus turns generics parity into premium wants, like once-weekly dosing that slashes clinic visits by 50%.

Rule 2: The Best Time to Position Your Drug Was in Phase I. The Next Best Time is Now.

Timing isn’t a luxury; it’s the difference between optionality and regret. Phase I/II choices - target effect size, comparator arms, even preliminary value props - lock in (or sabotage) your trajectory. Delay, and you’re handcuffed: Clinical teams chase easy, precedented endpoints, regulatory filings balloon, and market access hits walls built by indecision. My rule is a wake-up for those who want a good day: Engage Deep Positioning early to inject strategic oxygen, preserving flexibility amid market flux.

Expansion and Application: Pharma’s “valley of death” isn’t funding - it’s the positioning void between discovery and proof-of-concept. GSK’s Arexvy RSV vaccine exemplifies this: Phase I insights into older adults’ wants (e.g., single-dose simplicity) informed antibody persistence endpoints, yielding data that positioned it as the “preventive essential” pre-launch, gaining 70% share despite rivals. Contrast with delayed entrants like Moderna’s mRESVIA, which trailed due to later pivots.

Practically: Form cross-functional “positioning pods” in Phase I - R&D, commercial, HEOR working together and debating: “What effect size unlocks payer ROI?” This echoes my “Unmet Need is Not Fixed” thesis: Shape wants via early HCP advisory boards, quantifying how your asset evolves clinical paradigms. In 2025’s IRA era, where negotiations start 18 months pre-launch, this rule buys you the agility to adapt to HTA shifts, potentially lifting formulary odds by 25%.

Rule 3: Write ‘…Will Become’ at the Top of the Positioning, Not ‘Is’.

Static positioning statements - ”Our drug is a potent inhibitor” - are graveyards for ambition. My rule ignites foresight: Frame as “Our drug will become the first-line option for high-risk subgroups, backed by RWE on adherence gains.” This aspirational anchor isn’t a nice-to-have; it’s a directive, pulling teams toward evidence generation that realizes the vision. It transforms positioning from a descriptive echo chamber into a prophetic engine.

Expansion and Application: In physician decision-making, where 40% of preferences hinge on experiential “wants,” this future tense fosters narrative momentum. Eli Lilly’s Mounjaro (tirzepatide) mastered it: Early positioning as “the dual GIP/GLP-1 that will become the obesity standard” drove endpoint expansions into weight loss, evolving from diabetes “need” to blockbuster obesity want. Result? $5B sales in Year 1, reshaping markets.

For implementation: Draft a “will become” North Star in a one-page manifesto, shared quarterly. Link to KOL co-creation - envision subgroup benefits, then design trials (even pII trials) to prove them. This aligns with payer tactics: Pre-approval HEOR models project “will become” budget impacts, preempting denials. In saturated fields, it “creates” unmet need, like reframing statins as “will become” CVD preventives with novel biomarkers.

Rule 4: Find Your ‘Mechanism of Value’

Benefits are table stakes; value is the moat. This rule probes deeper than efficacy platitudes (”reduces A1c”) to the “why” that resonates: the Mechanism of Value (MoV) - that unique clinical-economic hook tying lab outcomes to stakeholder wins. It’s not a vague benefit ladder; it’s quantified proof of worth, demanding you dissect granular outcomes (e.g., “avoids 2 hospitalizations per 100 patients”) over abstract claims.

Expansion and Application: Payers reject 70% of new chronic therapies in Year 1 - MoV flips that by bridging academic discovery to real-world ROI. Pfizer’s Paxlovid hit it perfectly: MoV as “oral antiviral that accelerates recovery by 89%, slashing hospital burden“ wasn’t just antiviral potency; it was cost-offset mathematics for overwhelmed systems during COVID. This positioned it as indispensable, securing emergency access.

To operationalize: Map MoV via patient journey audits - identify “wants” like reduced caregiver time, then endpoint them (e.g., QALY gains). In oncology, it’s subgroup MoVs: “Will become the maintenance therapy extending PFS by 6 months in BRCA+.” Tools like budget impact models quantify it early, per Simon-Kucher benchmarks, ensuring your positioning withstands ICER scrutiny. You can easily see why this is a phase I/ phase II exercise - leaving these value endpoint explorations for phase III is too late.

Rule 5: Don’t Allow People to Position Your Drug Who Don’t Realise They’re Doing So

“Positioning by accident” is pharma’s silent killer: indication picks, sci-comm or medical affairs platforms, even brand names, set de facto frames of reference. My rule demands vigilance: Every market-shaping choice must be intentional, lest passive decisions (e.g., a narrow label) box you into commoditization.

Expansion and Application: Pseudo-positioning plagues 50% of underperformers - think drugs named for mechanisms (e.g., “Janus Kinase Inhibitor X”) that shout “me-too.” Amgen’s Prolia dodged this: Conscious early framing as “anti-sclerostin for bone health evolution” avoided osteoporosis generics traps, positioning as the “architectural” builder with $4B peaks.

Guardrails: Embed positioning reviews in governance - veto naming that hints at parity; evolve scientific platforms to “future-proof” narratives. Tie to HCP engagement: Unwitting KOL quotes can cement weak framings; curate them to amplify MoV. In payer plays, this means pre-filing dialogues framing your asset as “portfolio optimizer,” not “incremental cost.”

Additional Illustration: Bristol Myers Squibb’s Reblozyl (Luspatercept) – Pioneering EMAs to Upend Anemia’s ESA Monopoly

One of my favourites, because we were at the core of this…

In the transfusion-dependent anemia landscape - long beholden to erythropoiesis-stimulating agents (ESAs) like Amgen’s Epogen, which propped up early red blood cell progenitors but often fell short on durable responses - BMS revolutionaries at Acceleron challenged the foundational definition of “stimulation.” What if efficacy wasn’t about kickstarting production but maturing late-stage erythroblasts? This probe gave rise to Reblozyl, the first-in-class erythropoiesis maturation agent (EMA), approved in 2019 for beta-thalassemia and expanded in 2023 to myelodysplastic syndromes (MDS).

By reframing anemia treatment from “ESA stimulation” (with risks like tumor progression signals) to “EMA maturation” - evidenced by MEDALIST and BELIEVE trials showing 30–40% transfusion independence rates - Reblozyl didn’t just compete; it redefined the paradigm. Pre-launch KOL collaborations unpacked “unmet need” into dimensions like QoL beyond hemoglobin thresholds, while HEOR models quantified outlier ROI in ring sideroblasts+ MDS subsets.

The effect? ESAs’ market share eroded by 15–20% in key indications by 2025, with Reblozyl hitting $1B+ sales and inspiring follow-ons like Merck’s bomedemstat. This definitional change commoditized a $5B ESA duopoly, proving my rule: Interrogate terms like “anemia therapy,” and opportunity floods in - turning a niche biologic into a category creator.

Positioning as Your Revolutionary Edge

My five rules aren’t checkboxes; they’re a manifesto for pharma revolutionaries, echoing my “Rules for Pharma Revolutionaries” ethos of bold, early bets. In an era where wants eclipse fixed needs, they empower you to sculpt markets proactively - turning Phase I hunches into launch moats. The molecule doesn’t change; your decisions do.

In pharmaceutical positioning, where a single therapy can redefine lives - or slide into obscurity - “market shaping” is a potential secret weapon. It’s not the reactive scramble of post-launch marketing; it’s the proactive art of molding the therapeutic landscape before your product hits the pharmacy shelves.

As a strategist who’s been involved in, and dissected, launches from Lipitor’s blockbuster blueprint to Zevra’s orphan triumph, I’ve seen how real winners don’t just enter markets - they invent them.

If you’re tuned into the messages from my book Pharmaceutical Positioning, you know I’m fascinated by turning science into stories that stick. I’ll unpack market shaping through Gavi’s vaccine playbook (a global health masterclass) and four pharma-led pre-launch case studies that turned “what if” into billions.

But first: a fresh, actionable definition tailored for pharma professionals. Here’s the POSITION Model - my take on the classics, but with a guide to ecosystem engineering.

First of all, why do I use the word ‘ecosystem’? Well, it’s based on the essential challenge for market research - the market may not know what it wants before it gets it, and it’s certainly open to having its needs and wants shaped by an active participant.

That markets are malleable is no surprise, so it’s quite surprising that a lot of pre-launch models treat them as fixed. We tend to research future markets based on what people in present markets think, to use language that’s currently in use, and to work with existing economic models.

What Is Market Shaping? The POSITION Model

Market shaping in pharma is the deliberate orchestration of supply, demand, and stakeholder behaviors to preemptively resolve market failures - like undertreated diseases, stagnant guidelines, or payer skepticism - creating a fertile ground where your product doesn’t compete; it out-competes, asymmetrically. It’s about flipping “nice-to-have” into “non-negotiable,” often 3–5 years pre-filing, via levers like KOL alliances, evidence seeding, and regulatory nudges. The goal? Amplify unmet needs, create aspirational wants, and position your therapy as the ecosystem’s answer - driving adoption, loyalty, and ROI that compounds for decades.

To make it tactical, here’s the POSITION Model (a pharma-tuned evolution of systemic frameworks, zeroing in on pre-commercial precision):

• Prime the Paradigm: Redefine success metrics (e.g., “lower is better” for LDL) through data and KOL narratives, shifting baselines to expose gaps.

• Orchestrate Opinion Leaders: Rally KOL networks and advisory boards to co-author publications and symposia, seeding credibility and urgency.

• Shape Stakeholder Narratives: Craft tailored stories - evidence for HCPs, ROI for payers, empowerment for patients - to align incentives across silos.

• Influence Institutional Guidelines: Lobby for tighter targets or expanded criteria via advocacy and real-world evidence, embedding your “why now.”

• Target Therapeutic Gaps: Layer epidemiology and failure rates to spotlight unmet needs, turning statistics into emotional imperatives.

• Ignite Innovation Incentives: Advocate for regulatory fast-tracks (e.g., surrogates, orphans) and adjacencies to de-risk and broaden eligibility.

• Optimize Outcomes Evidence: Harness head-to-heads, RWEs, and health economic models to prove superiority and spillovers.

• Nurture Network Effects: Activate advocacy amplifiers and feedback loops to scale adoption, iterating for sustained momentum.

This model’s trying to do one thing: Transform market friction into your flywheel. Inefficient markets waste 40% of R&D spend; POSITION turns that into 3–5x returns by making your product the “inevitable” fix, the perfect fit for a market you just shaped.

Gavi’s Global Blueprint: Lessons for Pharma’s Pre-Launch Plays

Gavi, the Vaccine Alliance, isn’t pharma - but their two-decade shaping of fragile vaccine markets mirrors most pre-launch markets. Founded in 2000, they pooled demand from 70+ low-income countries to fix erratic supply and high prices, procuring 1.4B doses annually by 2025. Their Healthy Markets Framework (HMF, 2024 update) assesses supply/demand trade-offs, much like Phase 2 symposia gauge HCP gaps.

Spotlight: The pentavalent vaccine (diphtheria-tetanus-pertussis-HepB-Hib combo). In 2005, GSK’s monopoly priced it at $3.60/dose; coverage languished under 20%. Gavi’s phases - launch (volume guarantees to 100M doses), growth (Gates risk-shares with Serum Institute, tenders at $1.15–2.95), maturity (phased bids at $0.60–1.40, capacity to 600M) - slashed prices 75% to $0.85 by 2019.

Outcomes: 10M lives saved, $500M annual savings, suppliers from 1 to 8.

ROI? $21 health/economic return per $1 invested.

Gavi’s genius - patience (8–15 years), partnerships (WHO/UNICEF), monitoring (HMF/PRGs) - translates to pharma: Treat pre-launch as “Phase 0,” building resilient demand before the bell.

Pharma’s Pre-Launch Moves: Four Case Studies in POSITION

Now, the pharma cases: How Lipitor, Ozempic, Mounjaro, and Limpaspen wielded POSITION to engineer wants and needs. These aren’t hypotheticals - they’re quantifiable triumphs, proving pre-launch pays.

1. Pfizer’s Lipitor: Priming the “Lower is Better” Paradigm (1994–1997)

(You can revisit my post on Lipitor here… Lipitor: good, best, better)
Pfizer (via Warner-Lambert) didn’t chase statins where they were; they reshaped cholesterol management around more aggressive LDL targets, exposing rivals’ “modest” reductions as failures.

• POSITION in Action: Prime (NCEP targets changed from <130 to <100 mg/dL); Orchestrate (86K PCPs via a huge symposia program); Shape (70% “inadequate” narratives); Influence (FDA surrogates, saving $300M/2–3 years).

• Targeted Markets: Physicians (PCPs/KOLs); payers via guidelines.

• Value Proposition: “Fast, far LDL drops, lower is better - simple dosing for compliant wins.”

• Differentiation: “Potency king” at 10% lower price.

• Outcomes & ROI: $150B lifetime revenue; $12.9B peak (2006); 50%+ share, 10x category to $20B+; averted 4M CV events, $100B+ savings.

A consumer parallel:

Apple’s iPhone (2007 Launch): Priming a Paradigm Shift Like Lipitor’s “Lower is Better”

Apple’s iPhone didn’t enter the phone market - it created the smartphone era by reframing “touch is intuitive” as the new baseline, much like Pfizer redefined LDL targets to derive advantage from rivals’ newly established inadequacies. Pre-launch (2005–2007), Steve Jobs seeded developer kits to 1,000+ app creators (your KOLs), building an ecosystem before a single device shipped - echoing pharma’s advisory boards co-authoring publications.

• POSITION Parallels:

  • Prime the Paradigm: Teaser keynotes hyped multi-touch as revolutionary, shifting from physical keyboards (like tightening cholesterol guidelines).

  • Orchestrate Opinion Leaders: Influencers like tech bloggers got exclusives, seeding buzz via reviews (analogous to HCP symposia).

  • Influence Institutional Guidelines: Pushed carriers (e.g., AT&T) to adopt app stores, akin to lobbying FDA for surrogate endpoints.

• Outcomes: 6M units sold Year 1; spawned a $500B+ app economy. ROI? Apple’s market cap exploded 10x by 2012, averting “dumb phone” obsolescence.

• Pharma Tie-In: For a novel biologic, seed digital tools for HCPs pre-filing to “invent” adherence tracking as the gold standard.

2. Novo Nordisk’s Semaglutide (Ozempic/Wegovy): Obesity as Chronic Imperative (2017–2021)

Novo bootstrapped from diabetes to obesity, flipping “lifestyle” to “treatable disease” with $100M+ ecosystem spend.

• POSITION in Action: Prime (”GLP-1s modify disease” via 50+ NEJM papers); Orchestrate (200+ endo KOLs); Shape (40% undertreatment metas); Target (cardiometabolic risks); Ignite (FDA obesity labels).

• Targeted Markets: Physicians (endos/PCPs); patients via advocacy.

• Value Proposition: “15–20% loss + CV shield - disease, not symptoms.”

• Differentiation: “First chronic obesity Rx,” not a diet hack.

• Outcomes & ROI: $22.3B 2025 projection; 60.7% GLP-1 share; 300% script surge; averted 1M diabetes cases, $50B+ returns.

A consumer parallel:

Tesla’s Model 3 (2016–2017 Launch): Rallying Regulatory Allies and Igniting Wants Like Semaglutide’s Obesity Reframe

Tesla flipped EVs from eco-niche to mass aspiration by pre-selling 250K+ reservations in a week - mirroring Novo’s diabetes-to-obesity adjacency, where they amplified “chronic disease” needs via advocacy. Elon Musk’s live unveil (your regulatory fast-track) and influencer rides (KOL engagement) created FOMO, while lobbying for $7.5K tax credits shaped policy like ADA guideline tweaks.

• POSITION Parallels:

  • Ignite Innovation Incentives: Pre-order deposits ($1K each) de-risked production, like pharma’s EAPs generating RWEs.

  • Shape Stakeholder Narratives: Musk’s tweets and celeb endorsements (e.g., Joe Rogan) built “cool + sustainable” lore, targeting consumers (patients) and regulators (payers).

  • Nurture Network Effects: Software update teases post-reveal looped in early adopters, fostering community (like patient registries).

• Outcomes: 500K+ deliveries Year 1; EV market share from 1% to 10% by 2020. ROI? $400M pre-launch revenue from deposits alone, with $50B+ lifetime from Model 3 line.

• Pharma Tie-In: For a weight-loss therapy, use celebrity “transformation” stories and payer pilots to bootstrap from metabolic adjacencies, hitting 300% script growth.

3. Eli Lilly’s Tirzepatide (Mounjaro/Zepbound): Dual-Hormone Superiority Surge (2018–2022)

Lilly preempted GLP-1 fatigue by proving combinations are superior to singles, targeting “plateaued” patients.

• POSITION in Action: Prime (SURPASS head-to-heads, +2% A1c edge); Orchestrate (150+ KOLs, Medscape modules); Optimize (CVOTs for broad labels); Nurture (25% patient expansion loops).

• Targeted Markets: Physicians (specialists/PCPs); payers (HTA offsets).

• Value Proposition: “Deeper results, stall-breaker - 20%+ bonus loss.”

• Differentiation: “Hormone synergy” for unmatched multi-wins.

• Outcomes & ROI: $30.9B 2025 combo projection (50% Lilly revenue); H1 2025 $8.58B (+41% YoY); 25% patient expansion, $20B+ payer savings.

4. Zevra’s Arimoclomol (Limpaspen™): Orphan NPC Ecosystem Forge (2019–2024)

To a lesser-known example, in ultra-rare Niemann-Pick disease type C (NPC) (~1:100K births, no prior approvals), Zevra amplified “diagnostic odysseys” for a ~1K-patient U.S. market.

• POSITION in Action: Prime (30% progression delay biomarkers); Orchestrate (10–15 KOL board, 20+ AAN pubs); Shape (70% misdiagnosis stories); Influence (1K-signature FDA letter); Target (EAP RWEs).

• Targeted Markets: Physicians (neuro KOLs); patients (advocacy); payers (orphan precedents).

• Value Proposition: “Oral root-targeting—quality years extended.”

• Differentiation: “First-in-class” vs. off-label hassles.

• Outcomes & ROI: Q2 2025 $25.9M revenue (+486% YoY); H1 $46.3M + $150M PRV; 100+ patients Year 1, 20% diagnostic lift; 3–5x R&D ($100M) via $50M+ peak.

Your POSITION Toolkit: Landing your Pharmaceutical Positioning

Here’s how to operationalize:

Which Market Do You Mean? (Payers, Physicians, Patients?)

• Payers: Shape ROI narratives (e.g., Lipitor’s $100B savings) via HTA roadmaps - Gavi-style pooling for volume leverage.

• Physicians: Orchestrate KOLs early (Novo’s 200+ network) for guideline returns; Zevra’s niche board shows orphans scale via specialists.

• Patients: Target stories through advocacy (Zevra’s 1K signatures) - subtly, per regulations, to spark “empowerment wants.”

Value Proposition: From Features to Ecosystem Wins

Remember, ‘value proposition’ means stating your benefit in terms of value, but your product probably has different dimensions of value to different audiences:

• Bundle multi-wins (Lilly’s A1c + loss) with quantitative proof ($21:1 like Gavi) - test via pilots for sticky appeal.

• Co-create: Symposia feedback loops (Pfizer’s PCP dinners) ensure payer/HCP alignment.

• Spotlight spillovers: Guideline shifts (Novo’s 300% scripts) as “market multipliers.”

Making People Want/ Need What You Have: Igniting Desire and Differentiation

• Need Narrative: Epidemiology + failures (Zevra’s 70% delays) - data dashboards for urgency.

• Want Sparks: Head-to-heads (Lilly’s edges) + stories (patient EAP tales) - FOMO via “why now” symposia.

• Ruthless Differentiation: Own the pivot (Lipitor’s potency) - metrics like 2x adherence to moat out commoditized rivals.

Wrapping Up: POSITION Your Next Launch

The POSITION Model isn’t theory - it’s an edge in a 70% failure-rate game. From Gavi’s billions saved to Zevra’s 5x ROI, shaping turns obstacles to opportunity.

Shifting Perceptions Through MoA Reframing: Pharma Examples

There are compelling cases where evolving the description or understanding of a drug’s Mechanism of Action (MoA) or our term, Mechanism of Effect (MoE) - often via new data, label updates, or strategic positioning - has reshaped market dynamics.

This isn’t just scientific nuance; it’s a positioning lever that amplifies unmet needs, differentiates from competitors, and expands addressable markets. For instance, it can pivot a drug from “me-too” add-on to “paradigm-shifting” cornerstone, boosting adoption among HCPs, payers, and patients. A couple of examples from our own stable:

Reblozyl (luspatercept) is a great example: Its MoA as a first-in-class erythroid maturation agent (EMA) - binding TGF-β ligands to promote late-stage red blood cell maturation and reduce ineffective erythropoiesis - has been reframed from a niche anemia fixer to a transformative alternative to erythropoiesis-stimulating agents (ESAs).

Initially approved for transfusion-dependent beta-thalassemia (2019), the emphasis on its Smad2/3 signaling inhibition (vs. ESAs’ upstream stimulation) highlighted superior transfusion independence in MDS trials like MEDALIST (37% vs. 13% placebo). This MoA evolution, amplified in first-line MDS approval (2023), recaptured ~20% market share from ESAs amid biosimilar erosion, expanding the total addressable market by 30–40% to include ESA-naïve patients. Sales jumped 35% YoY in Q1 2025, projecting $2B+ peak, with payers viewing it as cost-saving (fewer transfusions = $50K–100K/patient savings).

Avastin (bevacizumab) is another classic: Launched as a VEGF-A monoclonal antibody inhibitor targeting tumor angiogenesis (2004, colorectal cancer), its MoA was initially framed as “starving tumors of blood supply” via endothelial disruption. Post-approval data revealed broader MoE, including direct antitumor cytotoxicity (e.g., immune modulation and vessel normalization), shifting perception from “narrow anti-angiogenic” to “multi-hit vascular disruptor.” This enabled label expansions (e.g., NSCLC, ovarian) and combo dominance, sustaining $7B+ annual sales despite 2011 breast cancer withdrawal. Market impact: Held 40–50% share in CRC despite competition, with reframing fueling 20% uptake growth in off-label ophthalmology (wet AMD) via intravitreal use - though supply disruptions (e.g., 2024 repackaging issues) highlight vulnerabilities.

Here are three more examples, drawn from cardio-metabolic and oncology spaces, where MoA/MoE evolution drove perception shifts and market gains. I’ve focused on quantifiable impacts for positioning relevance.

1. SGLT2 Inhibitors (e.g., Jardiance/Empagliflozin): From Glycemic Add-On to Cardiorenal Protector (2013–Ongoing)

• MoA Evolution: Initially positioned as insulin-independent glucose-lowering agents via proximal tubule SGLT2 blockade (promoting urinary glucose excretion, ~50–90g/day), reducing A1c by 0.5–1%. Post-2015 CVOTs (e.g., EMPA-REG OUTCOME) unveiled MoE beyond glycemia: natriuresis for volume reduction, anti-inflammatory effects on kidneys/heart (e.g., reduced glomerular hyperfiltration), and metabolic shifts (ketone utilization for cardiac efficiency). Reframed as “hemodynamic optimizers” with organ-protective signals.

• Market Perception Shift: From “third-line diabetes adjunct” (competing with DPP-4s) to “first-line disease-modifier” for T2D + HF/CKD, even in non-diabetics. Guidelines (ADA 2018+) prioritized SGLT2i for CV risk, flipping “weight-loss side effect” to core benefit.

• Impact: Global sales exploded from $2B (2016) to $15B+ (2024), with Jardiance alone hitting $5B in 2025 (up 25% YoY). Addressable market grew 3x to include 100M+ HF/CKD patients; payer ROI via 30–40% HF hospitalization cuts ($10K–20K savings/patient). Eli Lilly/Boehringer’s positioning via KOL-led symposia drove 50% endocrinologist preference.

2. Statins (e.g., Lipitor/Atorvastatin): From LDL-Lowering to Pleiotropic Powerhouse (1987–Ongoing)

• MoA Evolution: Core MoA is HMG-CoA reductase inhibition, slashing hepatic cholesterol synthesis and upregulating LDL receptors (40–60% LDL drop). Early 2000s data (e.g., JUPITER trial) highlighted pleiotropic MoE: anti-inflammatory (CRP reduction 30–50%), endothelial stabilization (NO synthase upregulation), and plaque regression - independent of lipid effects. Reframed from “cholesterol-buster” to “vascular healer” with multi-pathway CV risk modulation.

• Market Perception Shift: Transformed from secondary prevention staple to primary prevention essential, countering “only for high cholesterol” skepticism. NCEP/ESC guidelines tightened targets (e.g., <70 mg/dL for high-risk), emphasizing pleiotropics for non-lipid benefits like stroke prevention.

• Impact: Sustained $20B+ global market post-patent cliffs (Lipitor peaked $13B in 2006); pleiotropic narrative added 20–30% uptake in low-risk groups, averting 4M+ events and $100B+ savings. Pfizer’s pre-launch KOL priming (e.g., “lower is better”) amplified this, with generics inheriting the halo for 80% penetration.

3. Thalidomide (Revlimid Analogs in Myeloma): From Sedative to Anti-Angiogenic Immunomodulator (1950s–2000s Repositioning)

• MoA Evolution: Originally a sedative (1950s, withdrawn for teratogenicity), repurposed in 1990s as anti-angiogenic via cereblon binding (degrading transcription factors like IKZF1/3, inhibiting VEGF/IL-6 pathways). MoE expanded to immunomodulation (T-cell costimulation) and direct myeloma cell apoptosis, reframed from “anti-inflammatory curiosity” to “multi-target myeloma disruptor.”

• Market Perception Shift: From leprosy/ENL orphan to MM backbone (with dexamethasone), positioning as “immuno-angiogenic hybrid” vs. chemos. FDA/EMA approvals (2006+) and trials (e.g., MM-009) shifted HCP views from “risky relic” to “efficacy anchor.”

• Impact: Celgene’s Revlimid (lenalidomide analog) generated $12B peak sales (2019); expanded MM market 5x to $20B+, with 70% regimens including it. Repositioning via advocacy (e.g., IMF partnerships) drove 40% OS improvement perceptions, despite 2022 generic entry.

These cases show the role of the POSITION Model: Prime paradigms (e.g., SGLT2i’s “beyond A1c”), Influence guidelines (statins’ targets), and Optimize evidence (Avastin’s MoE data).