The great reprieve beckons but before the week comes to a close, we want to make sure you’re abreast of the major developments in healthcare. In this post, we’ll delve into the calls for resignations of FDA officials following approval of Biogen’s Aduhelm, the HHS pulling their contested 340B advisory opinion, and post-marketing studies being potentially required for breast cancer drugs.
The US Food and Drug Administration (FDA) "may require” or seek agreement from sponsors to conduct post-marketing studies to analyze long term effects of breast cancer drugs in both pre- and post-menopausal women in a final guidance issued on 17 June. The guidance also provides other considerations for sponsors as they plan for the inclusion of premenopausal women in clinical trials of drugs for breast cancer treatment. According to the agency’s announcement of the final guidance, historically, premenopausal women have been excluded from these trials, and in some cases, separate studies have been conducted in this patient population. Yet chemotherapy, immunotherapy and targeted therapies “have similar efficacy in pre- and post-menopausal women with breast cancer.”
The final guidance updates the previous version by providing more information on the type of long-term follow-up studies that should be conducted by sponsors. The final version states that “as warranted under applicable law or regulation, FDA may require, or seek agreement from the sponsor to conduct post-marketing studies to analyze additional long-term clinical effects.” The regulations under 21 CFR 312.85 covers Phase 4 postmarketing studies for investigational new drugs under the federal Food, Drug and Cosmetic Act. Another change from the draft guidance urges sponsors to ensure that trials are racially and ethnically diverse. It states that “clinical studies evaluating drugs in pre-menopausal women with breast cancer should reflect the racial and ethnic diversity of this patient population to support the assessment of short- and long-term effects of these therapies across clinically relevant subgroups of patients.” The guidance also encourages sponsors to meet with the Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research, as appropriate, to discuss their breast cancer drug development plans early in development.
Following the FDA’s approval of Biogen’s Alzheimer’s drug, Aduhelm, a Democratic lawmaker called for the Biden administration to remove the agency’s top decision-maker. Sen. Joe Manchin, D-West Virginia, called on President Joe Biden to oust the FDA’s interim commissioner Dr. Janet Woodcock and quickly nominate an “acceptable” permanent chief. Sen Manchin was bolstered by the approval of Aduhelm despite intense debate over treatment efficacy. The FDA's approval nod came after a resounding no vote from the agency’s independent advisors and since the approval, three members of the advisory committee have resigned. In addition to Sen Manchin, a consumer advocacy group, Public Citizen, said Woodcock, as well as CDER Director Patrizia Cavazzoni and Billy Dunn, director of the FDA’s neuroscience unit, should resign.
While calls for agency resignations run rampant, it is important to contextualize the FDA’s decision. Aduhelm has not been granted full approval from the FDA, it has received accelerated approval. Contrary to a full approval, accelerated approval allows for the early approval of a drug that treats a serious or life-threatening condition and fills an unmet medical need. Full approval of these accelerated therapies hinges on the measurement of surrogate endpoints, a measure of clinical benefit to the patients. Despite the controversy swarming the FDA’s decisions, two-thirds of Americans believe the therapy will be effective and most are excited to have access to a new treatment option, according to a poll performed by STAT and the Harris Poll. Patients with Alzheimer’s are desperate for treatment options and while Adulhelm has yet to consistently prove it’s clinical benefit, this approval is an opportunity to do so.
The Department of Health and Human Services has pulled a controversial advisory opinion that stated drug makers must provide products discounted under the 340B program to contract pharmacies after a heated legal fight with AstraZeneca. It is the latest court win for pharma companies in a nearly year-long dispute over contract pharmacies, which dispense drugs on behalf of 340B-covered entities. AstraZeneca had sued HHS last year over the opinion, which stated that the drugmaker and several others were violating federal law for not providing discounted drugs to contract pharmacies. AstraZeneca argued in the U.S. District Court for the District of Delaware that the advisory opinion violated federal law and HHS didn’t have the statutory authority to issue it. Last week, a federal judge struck down HHS’ motion to dismiss the lawsuit; however, since the opinion has been withdrawn, the lawsuit is moot.
340B requires drug makers to offer discounted products to safety net hospitals, community health centers and other providers in exchange for participation in Medicare and Medicaid. But drug companies claim the program has gotten too large and providers are not using the savings to help patients. Last year, 340B sales were $38 billion, or 7% of the U.S. prescription drug market, up from $29.9 billion in 2019. Contributing to this growth is hospitals and clinics buying medicines and then shipping them to retail and specialty pharmacies, instead of dispensing the drugs through their own in-house pharmacies. Drug makers imposed restrictions in an attempt to curtail discounts over duplicate billings, product diversions and ineligible rebates. While the HHS pulled its opinion, they have not withdrawn letters sent to AstraZeneca and five other drugmakers, calling for them to end the restrictions to contract pharmacies. The agency wrote that drug makers violated the federal 340B statute when they restricted sales to contract pharmacies. HRSA gave the companies until June 1 to respond and offer a plan to resume sales. If a drug company doesn’t do that then they could face monetary penalties. Eli Lilly, one of the other drug makers warned by HRSA, sued HRSA last month over the letter.