Findings in show that new formulations were more likely for blockbuster drugs and drugs that received accelerated approval. Proxy measures of clinical usefulness and other elements of therapeutic value were not associated with new formulations.
Findings in JAMA Health Forum show that new formulations were more likely for blockbuster drugs and drugs that got accelerated approval.
New formulations of drugs that are on the market and approved by the FDA can have some real advantages for patients, such as having to take a pill less often and that, in turn, can lead to greater adherence and presumably greater efficacy.
But new formulations can also be part of a deliberate business strategy by manufacturers to extend market exclusivity, protect sales and fend off competition from generics.
Study results published last week in JAMA Health Forum by Ravi Gupta, M.D., an internist and National Clinician Scholar at the University of Pennsylvania, and his colleagues, found that some proxy measures of therapeutic value were not associated with development of new formulations. They also identified a pattern of a sharp decrease in new formulations once a drug’s first generic was introduced.
Of the 65 new drugs in the study with at least one new formulation and a generic, 55 (85%) of the new formulations were approved before the first generic compared with just 10 (15%) approved after the first generic version was approved.
Taken together, their findings— and other previous research findings — suggest that manufacturers are “evergreening” their products to deflect competition, Gupta and his colleagues wrote.
“Policy makers should consider the rule of new formulations more carefully to incentivize therapeutically valuable innovation and minimize strategies to avoid generic competition,” they concluded.
Gupta and his colleagues acknowledged that their study did not assess the potential value of the new formulations. Another limitation is the study, as designed, couldn’t take into the account the possibility of a “deterrence effect” that a new formulation has on the development and commercialization of generics. As Gupta and his colleagues note, once a new formulation is approved, generic manufacturers may shift their efforts to developing generics of the new formulation.
To conduct their study, Gupta and his colleagues used an FDA database to identify all the news drugs in tablet or capsule form approved by the agency from 1995 to 2010.
New formulations were developed for 81 (40%) of the new 206 drugs they identified. Thirty-four (42%) of the new formulations were new dosage forms — extended-release formulations, for example — 29 (36%) were combination drugs and 13 (16%) were for new indications.
The researchers sifted through the data to identify which factors, if any, were associated with a drug being tinkered with into a new formulation. Their analysis found new formulations were more likely to be developed for drugs with $1 billion in sales (blockbuster drugs) and those that had received accelerated approval.
But they didn’t find any statistical correlation between the development of new formulations for drugs that were first-in-class or deemed a major advance (a proxy, they said, for innovation); drugs on the World Health Organization’s list of essential medicines (a proxy for clinical importance); or drugs that were rated highly by a French drug industry watchdog (a proxy for clinical usefulness).
Gupta R, Morten CJ, Zhu AY, Ramachandran R, Shah ND, Ross JS. Approvals and timing of new formulations of novel drugs approved by the US Food and Drug Administration between 1995 and 2010 and followed through 2021. JAMA Health Forum. 2022;3(5):e221096. doi:10.1001/jamahealthforum.2022.1096