A biotechnology company can demonstrate that a rare disease therapy works, receive regulatory approval and still encounter a fundamental commercial problem:
Will payers provide access to the patients physicians want to treat?
For high-cost rare disease therapies, that question should not first be asked during launch preparation.
By then, the clinical program may be complete, the evidence package largely fixed and the opportunity to generate additional data limited.
Market access should begin much earlier.
Regulatory Evidence and Payer Evidence Are Not the Same
Clinical trials are designed primarily to demonstrate safety and efficacy.
Payers are asking additional questions.
Which patients benefit most?
How meaningful is that benefit?
How durable is it?
What happens without treatment?
What therapies will patients otherwise receive?
Does treatment reduce hospitalizations, complications, monitoring, caregiver burden or use of other healthcare resources?
And perhaps most importantly:
Why should this therapy be used before a less expensive alternative?
A positive pivotal trial may not answer all of those questions.
The Existing Treatment Pathway Matters
Rare disease drugs rarely enter completely untreated markets.
Even when no therapy is approved specifically for the disease, physicians may already use steroids, immunosuppressants, antiseizure medications, supportive therapies, procedures or other off-label treatments.
Many of those alternatives are inexpensive.
That creates a challenge for a new high-cost therapy.
The relevant comparison may not simply be new therapy versus placebo.
Commercially, the comparison may be:
Why should the payer allow this therapy before the treatments already being used?
If the company wants its product used earlier in the treatment pathway, the evidence package should help answer that question.
Otherwise, payer policies may effectively determine treatment sequencing after launch.
HEOR Should Influence Development
Health economics and outcomes research is sometimes treated as evidence generated around commercialization.
In rare disease, it can be much more valuable when incorporated into development.
Consider what might matter beyond the primary clinical endpoint:
- Fewer hospitalizations.
- Reduced use of steroids or immunosuppressants.
- Less intensive monitoring.
- Fewer procedures.
- Reduced caregiver burden.
- Improved independence.
- Less travel to specialty centers.
- Fewer missed school or work days.
- Delayed disease progression.
- Reduced need for other therapies.
These outcomes can help describe the value of treatment in terms that matter to patients, physicians and payers.
But they can only be analyzed effectively if the appropriate information is collected.
Small Populations Make Evidence More Difficult
Rare disease creates another challenge: there may never be a large conventional dataset.
Patient populations can be small, geographically dispersed and clinically heterogeneous. Placebo-controlled trials may be difficult or ethically problematic. Disease progression may take years to observe.
That increases the importance of other evidence sources.
Natural-history studies, patient registries, real-world evidence and carefully constructed external controls may help explain disease progression and treatment impact.
These approaches require rigor.
But when designed early, they can strengthen both the clinical-development program and the eventual payer evidence package.
Patient Selection Affects Access
Payers frequently use the clinical-development program as a starting point for coverage criteria.
Age, disease severity, genetic confirmation, prior treatment and specialist involvement can all become part of authorization requirements.
That means patient selection during development can have downstream consequences.
A narrowly defined trial population may make regulatory interpretation easier but ultimately contribute to a narrow reimbursed population.
A broader population may increase the commercial opportunity but make demonstrating a clear treatment effect more difficult.
There is no universal answer.
The important point is that clinical-development decisions can eventually become market-access decisions.
Build the Access Strategy Backward
Before entering late-stage development, a rare disease company should begin asking:
- Which patients will we ask payers to cover?
- Where will the therapy sit in the treatment pathway?
- What less expensive treatments will payers expect patients to try first?
- What evidence would justify moving ahead of those therapies?
- What outcomes demonstrate value beyond the primary regulatory endpoint?
- What real-world or natural-history evidence should be collected now?
- What restrictions could materially reduce the reachable patient population?
These questions are easier to address while the development program can still generate evidence.
They become much harder after approval.
For rare disease therapies, market access does not begin when a price is established or a payer dossier is prepared.
It begins when the company decides what evidence to generate.
About PharmaKonsult
PharmaKonsult advises biotechnology leaders on the clinical-development and commercialization decisions that shape an asset’s future commercial value. Learn more about our biotech commercialization consulting services.
