The costs of Inhalation Pharmaceutical Development: Risks vs Rewards

The costs of Inhalation Pharmaceutical Development: Risks vs Rewards

April 14, 2020

How should regulations change to make orally inhaled nasal pharmaceutical products (OINDP) more affordable while keeping innovators willing to invest?

Khullar et al. recently published a paper in the NEJM on the lifecycle financials of pharmaceuticals; “Understanding the Rewards of Successful Drug Development Thinking Inside the Box”, Dhruv Khullar, M.D., M.P.P., Jennifer A. Ohn, M.P.H., Mark Trusheim, M.S., and Peter B. Bach, M.D., M.A.P.P., N Engl J Med 2020; 382:473-480 (DOI: 10.1056/NEJMhpr1911004;

Their paper looks at the impact on development costs and exclusivity rewards that successive US legislations have had. The fine balance between rewarding innovators for their pioneering work while widening access to cheaper therapies for the public is hard to strike. This is felt acutely in the OINDP space, where very few generics are available for market leading DPIs and pMDIs.

The failure rate of Gx OINDP from Phase 1 to approval is almost 90%. The hurdles for generic respiratory products are formidable: the only approved generic version (Wixela Inhub®) of the blockbuster Advair took 10 years and over $700 million in development. A similar program at Sandoz was abandoned after more than a decade and over $440 million cost. A large portion of these efforts was on bioequivalence trials. A price tag of $100M to develop a single strength pMDI is not unheard of.

A key reason for the requirement of bioequivalence trials is the absence of a mandatory process for the innovators to publish their quality control information and provide reference standards. Compliance with such a program would enable timely development of generic products at a lower cost and risk. Clearly, a win for the public and generic manufacturers.

But what should be the incentives for innovators to comply with a program that reduces the hurdles for entry of generic products? Clearly there needs to be a win for innovators, and if that win also results in a win for patients with more rapid development of novel therapeutics, then that just might provide the balance needed for change. Innovators could be rewarded with additional market exclusivity or priority review vouchers for compliance with the program. But this wouldn’t accelerate development of new therapeutics, only provide greater clarity on the duration of their market exclusivity.

The development program for any new inhaled therapeutic is costly, and fraught with risk of failure . What mechanisms could be taken by the regulators to reduce development time and risk for innovative inhaled products without sacrificing quality?

Igor Gonda, David Cipolla and I, Philippe, believe significant changes are needed to make therapies more affordable while providing adequate incentives for innovators in the OINDP space.

What do you think?
Should the FDA demand USP manuscripts from originators for the introduction of Generics?

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