Pharma companies may have a winning asset, a winning development plan and an important disease target with unmet needs, but only one product can be first to market, only one can be the most efficacious and only one will become the standard of care. If your asset is entering a disease area with similar efficacy to an established standard of care, or if your asset is one of multiple products in a class entering within one to two years of one another, it’s critical to have a clear understanding of what it will take to meaningfully differentiate, and to do this early enough—in phase I or II—so there's enough time to correct the development plan.


In our last blog post, we shared four potential paths to clinical differentiation. Here we explore the first two: raising the bar and precision play. To be successful in these paths, here are two steps to take earlier in the development process:


1. Define meaningful differentiation and whether your product can raise the bar. This step requires talking to customers about what it takes to truly raise the bar on efficacy and what evidence they need to see to believe it. Customers aren’t just future prescribers: Regulatory agencies, local payers, national payers and patients may all need to be evaluated. There have been many examples of products launching with a numerical difference in efficacy, but the difference was too small to overcome habit, favorable reimbursement and established brand heritage. Crestor vs. Lipitor is a classic example. Despite a head-to-head study showing a small improvement in lowering cholesterol, cardiovascular outcomes of the two drugs were similar, and thus the efficacy improvements were not enough for Crestor share to come close to Lipitor while both were on patent.


Evidence plans matter here as well. Demonstrating superior outcomes may only matter in commercial success if you can talk about it. At a minimum, you need to select the target population, comparator, and primary and secondary endpoints for your registrational trial that will resonate with prescribers and payers. There are very few disease states where placebo is still a meaningful comparator.


2. Identify if your product can make a “precision play” and be the best for some—not all— patients. This is a mindset shift from a “compare and win” strategy to a “problem/solution” strategy: defining a problem within a disease area and designing your evidence plan to solve for it. To do this requires a clear definition of your target patient population and market positioning before your registrational trial, and shaping inclusion/exclusion criteria and endpoints to demonstrate superiority in this population.


Of course, creating a narrower target population for your product can seem like a self-defeating exercise. Why limit how my product can be used? There are two circumstances in which taking this approach can create rather than destroy value:

  • You can have the opportunity to capture the majority of that patient population. If your product overperforms when a common patient characteristic is present, you may be able to beat the outcomes of an otherwise undifferentiated competitor by having a clinical trial patient population that plays to your product’s strengths. Look at early clinical data for stratifications that show big differences, and size the population defined by these stratifications. Do the math on whether a big slice of the smaller pie is better than a small slice of the larger pie. Even if the indication isn’t limited, your evidence strategy can be developed to show strong evidence in a sub-population (registries and real-world data can develop evidence post-launch as well).
  • You’re going to be positioned there, anyway. HCPs and payers alike look for clarity in the use cases for new products to define their value and place in the armamentarium. If your product is likely to be relegated to a certain population anyway, play into the desire for clarity by developing evidence in that population on which you can promote. HCPs adopt products more quickly when they clearly understand where and when to use them. Products with narrower patient targets have more leverage for coverage and reimbursement with payers because the balance sheet impact is projected to be smaller. There have been many examples of products developing evidence to own a specific patient population: Keytruda in PD1-high and now MSI-high, Cymbalta in patients with both pain and depression, carbapenems in patients with serious hospital-acquired infections, and others. You can let your customers relegate you to that population, or you can seek to clarify the opportunity and own it.