Study: Blockbuster, accelerated approval drugs more likely to get new FDA-approved formulation

Regulatory NewsRegulatory News | 23 May 2022 |  By 

Drugs with blockbuster status and those approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway were more likely to receive a new formulation, while other factors like clinical effectiveness were not predictive of reformulation, according to a recent study published in JAMA Health Forum.
“This study reinforces concerns that manufacturers are using evergreening strategies to maintain revenue and avoid generic competition,” Ravi Gupta, MD, of the National Clinician Scholars Program at the University of Pennsylvania in Philadelphia, and colleagues wrote in their study. “It suggests that policy makers should consider the role of new formulations more carefully to incentivize therapeutically valuable innovation and minimize strategies to avoid generic competition.”
Gupta and colleagues evaluated the rate of reformulation for 206 approved novel tablet and capsule drugs in the Drugs@FDA database between 1995 and 2010, noting sales status of the drug as well as if the drug had been approved under the accelerated approval pathway, was on the list of the World Health Organization’s essential medicines, was considered innovative (first in class or advance in class), and was clinically useful.
Of the 206 novel approved drugs, 79 drugs (38.4%) had achieved blockbuster status with more than $1 billion in sales, 178 drugs (86.4%) were not approved under the accelerated approval pathway, 160 drugs (77.7%) were not on the WHO’s essential medicine list, 90 drugs were first-in-class or advance-in-class drugs (43.67%), 66 drugs (32.0%) were deemed clinically useful as rated by the independent non-profit Prescrire International, and 172 drugs (83.5%) were not orphan drugs. The therapeutic areas of each drug comprised autoimmune or musculoskeletal (6.8%), cancer (12.1%), cardiovascular or diabetes (18.9%), gastrointestinal (7.3%), genitourinary (8.7%), infectious disease (17.5%), neurology (16.0%), psychiatry (8.3%), or other specialties.
Gupta and colleagues found 81 drugs (39.3%) had a new FDA-approved formulation as of December 2021, with 167 of those drugs (81.1%) having a generic formulation. Most drugs with new formulations were approved before the novel drug’s generic approval compared to after a generic approval (84.6% vs. 15.4%; P < .001).
Drugs that had achieved blockbuster status were significantly associated with new formulations compared to drugs that did not achieve blockbuster status (58.2% vs. 27.6%; adjusted OR, 4.72; 95% CI, 2.26-9.87; P < .001). Drugs that received accelerated approval were also significantly more likely to receive a new FDA-approved formulation compared to drugs not approved under the accelerated approval pathway (50.0% vs. 37.6%; aOR, 5.48; 95% CI, 1.52-19.67; P = .009). New formulations were significantly less likely among orphan drugs compared to non-orphan drugs (11.8% vs. 44.8%; aOR, 0.13; 95% CI, 0.03-0.52; P = .004).
Factors that didn’t significantly impact likelihood of reformulation were being listed as a WHO essential medicine (47.8% vs. 36.9%; aOR, 1.32; 95% CI, 0.52-3.34; P = .56), being a first-in-class or advance-in-class medication (37.8% vs. 40.5%; aOR, 0.71; 95% CI, 0.32-1.58; P = .40), or clinically usefulness (40.9% vs. 44.8%; aOR, 0.81; 95% CI, 0.34-1.92; P = .64), the authors said.
“Taken together, these results suggest that revenue is a substantial driver of whether and when a manufacturer secures FDA approval of the first new formulation of existing drugs, reinforcing concerns that manufacturers are using evergreening strategies to maintain revenue and avoid generic competition,” Gupta and colleagues said.
The authors suggested that the decline in new formulations after generic approval implies manufacturers time new formulations. “Once specific drug markets face generic competition, new formulations are far less common, indicating a possible diminishment of manufacturers’ ability or interest to continue incremental innovation,” they said.
“The present findings highlight the importance of reforming incentives to encourage more meaningful pharmaceutical innovation,” Gupta and colleagues concluded.
JAMA Health Forum Gupta et al.


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