Biosimilars have been slow to enter the US market for complex reasons ranging from the manipulation of patent protections to brand-name drug rebates. Now a new analysis, published in the Mayo Clinic Proceedings, suggests that a “high testing bar” for biosimilars to gain regulatory approval is another contributing factor.
The analysis found that the median time from the start of a Phase I study to approval by the US Food and Drug Administration (FDA) was more than 5 years.
In 2010, US lawmakers sought to speed the entry of biosimilars through the passage of the Biologics Price Competition and Innovation Act (BPCIA), which created an abbreviated approval pathway for products that could demonstrate high similarity to originator biologics without clinical differences in safety, purity, and potency.
But the legislation has not brought a flood of biosimilars to the market. As of 1 May 2020, the FDA has approved just 26 biosimilars, of which 17 products have been marketed. In contrast, the European Medicines Agency has approved 64 biosimilars through its abbreviated pathway program, which was created 6 years before the BPCIA.
“The BPCIA pathway was intended to accelerate biosimilar approvals, yet in the first 3 years of its implementation, most biosimilars underwent Phase III testing, taking on average almost 2 years to complete,” wrote ChangWon C. Lee and colleagues at the Program on Regulation, Therapeutics, and Law (PORTAL) at Brigham and Women’s Hospital and Harvard Medical School in Boston. “Although this time was shorter than the contemporaneous 40-month median Phase III clinical time for originator drugs, it reveals that extensive pre-approval biosimilar clinical testing was common.”
Using the commercial pharmaceutical pipelines database Pharmaprojects, researchers identified all biosimilar products that started Phase I or I/II testing between 2012 and 2015. Overall, they found 40 biosimilars that began testing during that timeframe. By October 2019, half of the products had received FDA approval, 16 were under development, and four had been discontinued or suspended for commercial reasons.
The median length of a Phase I trial was 6 months, a Phase II trial was 22.8 months, and a Phase III trial was 22.1 months. However, biosimilars with cancer indications typically had longer-running Phase III trials, compared with non-cancer indications (32.9 months vs. 20.2 months, P less than .01).
The median clinical development time from Phase I to Phase III testing was 48 months for the 30 biosimilars with ongoing or completed Phase III trials. Among the 20 biosimilar that were approved by the FDA during the study period, the median time from the start of Phase I testing to the date of approval was 69.9 months, or more than 5 years.
The researchers gave a nod to the FDA for its work to improve the efficiency of pre-approval testing, but noted that if additional efficiency can’t be achieved it may be time to consider subsidies for biosimilar testing. “[S]pecial subsidies for pre-approval biosimilar clinical testing may be warranted to ensure sufficient market entrants and thus improve patient access to affordable biotherapeutics,” they wrote.
The research was funded by Arnold Ventures. Two of the study authors received additional support from the Harvard-MIT Center for Regulatory Science and the Engelberg Foundation.
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