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Stakeholders weigh in on direction for US FDA biosimilar insulin pathway


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Stakeholders weigh in on direction for US FDA biosimilar insulin pathway

The U.S. Food and Drug Administration heard from drugmakers, patients and other stakeholders on whether the agency should treat products intended to be lower-cost versions of insulins any differently in the regulatory process than cheaper forms of complex biologic medicines.

The FDA is up against a deadline to have its processes in place to approve lower-cost insulins that will be deemed biosimilars, meaning they are essentially the same as the branded products but less expensive.

The agency convened a public hearing May 13 to gain input on the best path forward.

For historical reasons, the FDA has used its new drug approval process to approve insulin and certain other proteins, such as human growth hormones.

But starting March 23, 2020, the applications for insulin and other protein products must go through the FDA's biologic licensing process for approvals — a transition Congress mandated under the Biologics Price Competition and Innovation Act.

That 2010 law, which was adopted as part of the Affordable Care Act, granted the FDA the authority to approve biosimilars.

Unlike biologic therapies — complex molecules derived from living cells — such as AbbVie Inc.'s arthritis monoclonal antibody Humira, insulin is a relatively simple protein, a number of stakeholders noted at the FDA's public hearing.

Rising costs

Insulin has been used for nearly 100 years in treating patients with diabetes, a disease that affects about 30 million Americans, or about 9.4% of the U.S. population, according to the U.S. Centers for Disease Control and Prevention.

But insulin prices have sharply increased in recent years, putting the medicines out of reach for many American patients with diabetes.

Insulin costs have been at the center of a number of hearings on Capitol Hill in recent months, including an April 10 House session, where executives from Eli Lilly and Co., Novo Nordisk A/S and Sanofi testified. The three drugmakers make up 90% of the global insulin market.

The House and the Senate both have ongoing bipartisan investigations into insulin prices.


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Ned Sharpless

Source: FDA

The FDA's May 13 meeting focused not only on obtaining input on setting up the scientific standards for evaluating applications for biosimilar insulins, but also for what it will take for manufacturers to meet the requirements of interchangeability — a status allowing pharmacists to switch the lower-cost product for the innovator drug without notifying the prescriber.

Late last week, the FDA finalized its interchangeability guidelines — the roadmap biosimilar makers have been waiting for since 2010, though the agency issued a draft document two years ago.

None of the 19 U.S.-approved biosimilars currently carries the interchangeable status.

Having that designation could translate into increased competition, lower costs and more access to the drugs for patients, FDA Acting Commissioner Ned Sharpless said at the May 13 hearing.

He noted that the FDA has granted either full approval or tentative approval to three follow-on versions of brand-name insulins, though those lower-cost products are not yet considered biosimilars in the U.S. because the transition process was not yet in place when regulators cleared their applications.

Stakeholder feedback

Christine Simmon, senior vice president at the Association for Accessible Medicines, a lobbying group, and the executive director of its Biosimilars Council, urged the FDA to emphasize that interchangeability does not confer quality but is a statutory standard for automatic substitution.

Simmon accused the brand-name industry of engaging in a misinformation campaign, in which patients are told they must not transition from their innovator biologic to a biosimilar until it has the interchangeable status — a designation many are unlikely to seek.

Mariana Socal, an assistant scientist at Johns Hopkins University, said the biosimilarity and interchangeability criteria that were intended for large molecules should not be blindly applied to older and smaller molecules such as insulin.

"Insulin is not Humira," she told the FDA.

Socal also said the regulatory complexity of having two separate designations for lower-cost insulins — biosimilar and interchangeable — would be confusing for patients with diabetes and would do more harm than good.

The FDA should consider insulin to be an exceptional product for which the interchangeability rules should be carefully reinterpreted, if applied at all, Socal said.

Abhijit Barve, head of global clinical research at Mylan NV, told the FDA that the scientific considerations for biosimilar insulins should be no different than how the follow-on products are currently approved under the agency's 505(b)(2) pathway, which permits regulators to rely on a previous finding of safety and effectiveness that led to approval of the branded product or on data not developed by the applicant, such as published literature.

Adding the interchangeability status is simply another layer of regulatory complexity, he said.

Jing Luo, an internal medicine doctor at Brigham and Women's Hospital and an instructor at Harvard University, said biosimilar insulin makers should only be required to conduct small switching studies to demonstrate their products are interchangeable at the pharmacy.

But Sherry Martin, vice president of diabetes global medical affairs at Lilly, insisted switching studies are critical and provide additional confidence that there will be no meaningful increase in immunogenicity — provoking an immune response in which the drug is less effective — when alternating between the biosimilar and brand-name product. She said the FDA should take steps to ensure that the conduct of switching studies is efficient and feasible.

Lilly expects the future of diabetes care to consist of connected ecosystems made up of insulin, digital health technologies and connected delivery systems, Martin said.

In assessing interchangeability, the FDA should consider whether a company has its own connected ecosystem and how its components compare with those of the brand-name product, she said. Regulators should also evaluate how patient outcomes compare between systems and if switching from a product within one ecosystem to another affects the continuity and stability of care for the patient and the data link to their healthcare team, Martin said.