The FDA will hasten the review of two more new Alzheimer's drug candidates, Eli Lilly & Co.'s donanemab and Biogen and Eisai's lecanemab.
Today, the experimental Eli Lilly drug donanemab received the FDA’s “breakthrough therapy designation” based on its potential to treat Alzheimer’s disease. The FDA granted the same accelerated designation to lecanemab, a drug being developed by Biogen and Eisai, earlier this week. Both are designed to fight Alzheimer’s by reducing the presence of the disease’s hallmark beta-amyloid protein aggregations in the brain.
Their endings, –mab, are shorthand for monoclonal antibodies, which are laboratory-made proteins that mimic the immune system’s defensive abilities, and their accelerated approval processes follow big news this month on another –mab: Biogen’s controversial aducanumab, brand name Aduhelm.
Aducanumab (Aduhelm) was approved on June 7 for the treatment of Alzheimer’s after receiving its own FDA breakthrough status designation, making it the first-ever FDA-approved drug designed to modify Alzheimer’s pathology. While its approval was deeply contested due to lack of efficacy data, many believed the move would benefit Alzheimer’s drug research and development at large — particularly drugs designed around the amyloid hypothesis that reducing this hallmark protein in the brain can effectively address the disease. With these two new FDA actions, it seems these benefits are already playing out.
(In February 2024, Biogen took Aduhelm off the market indefinitely.)
The FDA established its breakthrough therapy designation as a way to accelerate the development and review of drugs underway for serious or life-threatening illnesses. Receiving this designation is not an indication that the drug will be ultimately be found to be safe and effective nor that the FDA will definitely approve the drug in question.
What’s next for Eli Lilly’s experimental Alzheimer’s drug donanemab?
Eli Lilly’s TRAILBLAZER-ALZ Phase 2 trial was a relatively small, randomized, placebo-controlled, double-blind study measuring the safety, tolerability and efficacy of donanemab in patients with early symptomatic Alzheimer’s.
Trial results announced in early 2021 indicated that donanemab slowed down cognitive decline by 32 percent compared to the placebo, meaning that people with symptomatic Alzheimer’s in the trial sustained the same level of cognitive skills after 18 months of donanemab treatment as the placebo group showed after 12 months.
The drug “has been shown to rapidly result in high levels of amyloid plaque clearance, as measured by amyloid imaging,” the company said in a January press release.
According to MarketWatch, Lilly issued a statement on Thursday that the company intends to submit a biologics license application for donanemab later this year, prompting analysts to share insights with the drug company’s investors. One analyst from Stifel Financial Corp., Paul Matteis, said in a note to investors that despite that the drug’s data is “less confusing” than its predecessor aducanumab, Lilly’s intention to seek approval in 2021 “is somewhat surprising to us from a timing perspective,” and that he is unsure as to whether the FDA will find the data adequate.
What’s next for Biogen and Eisai’s experimental Alzheimer’s drug lecanemab?
The FDA decided to speed up the agency’s evaluation process of Biogen and Eisai’s lecanemab after reviewing what it considered promising data from a Phase 2-B clinical trial. The trial tested lecanemab’s ability to reduce aggregations of beta-amyloid in the brain — like Aduhelm is designed to — and to reduce clinical decline among the trial’s 856 patients, who had early signs of Alzheimer’s including mild cognitive impairment and early amyloid pathology.
The trial results, presented at the 2021 Alzheimer’s Disease and Parkinson’s Disease Conference, indicate the drug did help clear beta-amyloid from the brain. The drug is now in Phase 3 trials, being tested across 1,795 patients with early Alzheimer’s.
What does this news mean for Aduhelm?
Critics of the FDA’s approval of Aduhelm say the drug’s human trials have failed to demonstrate that the drug is effective, and that its estimated cost of $56,000 per year is excessive — a burden to patients and to the Medicare system.
Should lecanemab and donanemab ultimately earn FDA approval, some analysts speculate that their availability could force a reduction in Aduhelm’s sky-high price tag.
UPDATE: 3 March 2024, 9:01 P.M. ET. In February 2024, Biogen took Aduhelm off the market, citing financial concerns. Although the drug did receive accelerated, conditional FDA approval for the treatment of early Alzheimer’s disease in 2021, it is no longer available to new patients. The company announced it would sunset trials in May 2024 and cease supplying the drug to current patients in November 2024.
