FDA proposes waiving clinical trial requirements to bring biosimilars to market faster
The Trump administration's latest effort to lower drug costs is extending to biosimilars, drugs that are closely similar to biological drugs made from or isolated from living organisms such as cells. Just as generic drugs are cheaper versions of brand-name products, biosimilars are lower-cost versions of complex biological drugs. But there are important differences in how these drugs are tested and reviewed.
Generic drugs, such as small molecule pills, only need to demonstrate bioequivalence to a reference product (original drug). No clinical trials are required to support an FDA submission. Since the first biosimilars were approved by the FDA in 2015, the drugs have needed to undergo clinical testing before they can show efficacy comparable to the original drugs. Comparative efficacy studies (CES) are long and expensive. The tests can take up to three years and cost an average of $24 million, according to the FDA. The time a biosimilar spends in these studies is the amount of time patients need to continue taking the more expensive brand-name biologic.
The FDA announced draft guidance Wednesday to reduce what it calls “unnecessary clinical testing” of biosimilars. The regulator proposes that biosimilar manufacturers be allowed to use analytical testing in place of these studies. In the draft guidance, the FDA said the agency has gained extensive experience in evaluating analytical differences between proposed biosimilars and their reference products and understanding the impact of these differences on the clinical performance of the product.
“In addition, currently available analytical techniques can structurally characterize highly purified therapeutic proteins and model in vivo functional effects with high specificity and sensitivity using in vitro biological and biochemical assays,” the guidance states. “Comparative analytical assessments (CAA) are generally more sensitive than CES and can detect differences between two products (if differences exist), which may hinder demonstration of biosimilarity.”
Some biosimilars undergo “switch studies,” which are additional clinical trials designed to show that switching from a reference product to a biosimilar does not increase safety risks or reduce efficacy. These studies are conducted for drugs that need to demonstrate interchangeability with brand-name products. Biosimilar insulins are examples of products that have been researched to be interchangeable. Generic drugs do not require interchangeability testing. The FDA said in a statement Wednesday that these additional tests could slow development and create confusion among the public about the safety of biosimilars. Regulators now say conversion studies are generally not recommended.
A faster regulatory path for biosimilars could have huge financial implications for patients. Biologic drugs include pricey AbbVie's immunology drug Humira, which in its heyday was the most prescribed and expensive drug on the market. A lower-cost biosimilar version of Humira is due to be launched in 2023. The FDA calculates that biologic drugs account for only 5% of U.S. prescription drugs but will account for 51% of total drug spending by 2024.
To date, the FDA has approved 76 biosimilars. The FDA said that of the biologic drugs expected to lose patent protection in the next decade, only about 10% of biosimilars are currently in development. In the FDA announcement, Commissioner Marty Makary said biosimilars have the potential to significantly reduce health care costs.
“By streamlining the biosimilar development process and helping to increase interchangeability, we can significantly reduce the cost of advanced treatments for cancer, autoimmune diseases and rare diseases that affect millions of Americans,” Makary said.
The draft guidance, “Scientific Considerations for Demonstrating Biosimilarity of Reference Products: Updated Recommendations for Assessing the Need for Comparative Effectiveness Studies,” is open for comment over the next 60 days. Electronic comments may be submitted here .
The FDA's announcement of biosimilars follows the agency's launch of an initiative targeting generic drugs. In early October, Makary announced a pilot program to allow for faster regulatory review of generic drugs undergoing bioequivalence testing in the United States. Eligible drugs must also be manufactured in the United States using domestic APIs.
Photo: Getty Images, Sarah Silbig
