Alzheimer’s Disease Drug Donanemab Gets Backing From FDA Expert Panel

A Meals and Drug Administration knowledgeable panel of advisors voted 11-0 yesterday to advocate that the company approve the Alzheimer’s illness drug donanemab. The panel concluded that the therapeutic is efficient in treating the memory-robbing situation in sufferers with delicate cognitive impairment and early-stage dementia and that the drug’s advantages outweigh the dangers.

The panel did, nevertheless, elevate issues about sure security dangers and inadequate illustration of Hispanic and Black sufferers within the Part 3 trial.

The FDA will quickly resolve on donanemab’s advertising authorization. Although the company isn’t required to comply with the suggestions of its advisory committees, it normally does, through which case donanemab would turn into the third beta amyloid-directed monoclonal antibody accepted within the U.S.

Practically seven million People live with Alzheimer’s, roughly two million of whom are within the early phases of the illness. Illness-altering therapies have solely just lately turn into obtainable. All three accepted monoclonal antibodies—clones of human antibodies—are the primary disease-modifying therapies for AD that gradual medical decline by lowering beta amyloid plaque within the mind. Amyloid plaques are accumulations of beta amyloid proteins that clump collectively between the neurons within the brains of AD sufferers. Physicians verify the existence of beta amyloid plaque in sufferers by performing mind scans.

The primary beta amyloid-directed biologic, Aduhelm (aducanumab), underwent an awfully controversial approval course of in 2020 and 2021 through which the FDA ignored recommendation given by an impartial advisory committee to not approve the therapeutic. The FDA by no means gave a compelling justification for its resolution.

After this controversy, the Facilities for Medicare and Medicaid Companies issued a nationwide protection dedication in April 2022 that severely restricted protection of all beta amyloid-directed monoclonal antibodies except they’d common, versus accelerated, approval by the FDA and had been deemed to supply at the very least some clinically significant profit.

As soon as the FDA granted common approval of the second biologic, Leqembi (lecanemab), in July 2023, CMS lifted most restrictions, paving the best way for reimbursement as long as Medicare beneficiaries who take Leqembi enroll in a affected person registry to gather extra information on the drug. Medicare is the predominant payer for AD diagnostics and prescribed drugs.

Leqembi and donanemab aren’t cures. They’re modestly efficient in lessening cognitive decline.

The Part 3 medical trial for donanemab measured cognitive impairment in folks with gathered beta amyloid plaque and totally different ranges of the tau biomarker. After 76 weeks of remedy, researchers discovered that donanemab had considerably slowed cognitive and practical decline. Particularly, the research trial confirmed that donanemab slowed progressive impairment by 35% for these with low and medium ranges of tau and 22% for your complete inhabitants, when in comparison with these on placebo. Furthermore, individuals taking donanemab skilled a 39% decrease threat of progressing to the following stage of illness in comparison with placebo.

Panelists contemplating the proof advised that there was sufficient slowing of cognitive decline to be “significant” to sufferers, based on NPR.

There are lingering questions relating to exactly what the label will seem like as soon as the FDA makes its anticipated approval resolution.

For instance, the FDA will nonetheless have to weigh whether or not donanemab needs to be limited to individuals who have deposits of tau of their brains. If that’s the case, a PET scan could be essential to detect tau, as Neurology Stay reported. Advisors cautioned on Monday that such a requirement might current a hurdle to affected person entry to remedy, as such scans are expensive and time consuming.

And so, Biopharma Dive reported, that the advisors need “extra readability concerning the position the tau biomarker would play in medical decision-making if the drug will get accepted.”

Additionally, the FDA had requested the panel to supply steering on whether or not and when it’s protected for folks to cease taking donanemab primarily based on reductions in beta amyloid plaque. The drug’s developer and producer, Eli Lilly, notes that its proposed dosing routine—700 mg intravenous infusion each 4 weeks, adopted by 1,400 mg each 4 weeks—could also be stopped as soon as the plaque is cleared.

Whereas in precept some panelists favored the thought of stopping remedy, in addition they requested whether or not discontinuation would essentially be prudent. What would occur, one panelist requested, if amyloid started accumulating once more in sufferers’ brains?

On the drug’s security, the advisors expressed issues concerning the dangers of delicate mind swelling which will end result from donanemab and different beta amyloid-directed monoclonal antibodies.

The panel raised particular questions concerning the drug’s doable causal position in amyloid-related imaging abnormalities, which had been present in practically 25% of sufferers within the Part 3 research.

Previous to the advisory committee assembly, the FDA posted a briefing doc that pointed to an “imbalance in deaths” in sufferers handled with donanemab. Nonetheless, “there was no uncommon grouping of deaths that may counsel a causal relationship.”

For folks at excessive threat of ARIA, equivalent to these with a genetic marker named APOE4, Eli Lilly recommends nearer monitoring.

The already accepted AD drug Leqembi has a black field warning. It might appear doubtless that donanemab will even be tagged with such a warning on the label.

Lastly, FDA advisors said that extra information is required to discover how properly the drug performs in underrepresented teams within the medical trials, together with Black and Hispanic sufferers. Of the 1,736 folks enrolled within the Part 3 trial, solely 35 had been Black and 59 Hispanic individuals, representing simply 5% of the entire.

The FDA advisory committee’s unanimous resolution that donanemab’s general risk-benefit profile is favorable bodes properly for its final approval. In flip, this would offer AD sufferers and their caregivers one other remedy possibility in a therapeutic space with a substantial quantity of unmet want.