On Monday, a 17-year drought in the Alzheimer’s drug world ended with FDA approval of Biogens Aduhlem (aducanumab). The controversy behind the FDA’s decision was considerable, but it doesn’t seem to alarm drug developers, who are now narrowing down to degenerative brain disease.
In short, Aduhelm’s approval came after conflicting results from clinical trials. in the November 2020 An independent FDA advisory panel did not recommend the agency endorsing the drug, but in June the agency still approved the drug through an accelerated approval program.
Aduhelm is now the first novel treatment to address one of the underlying causes of Alzheimer’s – beta-amyloid plaques that build up in the brain.
The drug received support from Patient and industry groups (the FDA too noticed that “the need for treatment is urgent” in a statement on the choice of agency). Still, there are a number of doctors who have raised concerns. A member of the panel of experts who voted against approving Aduhelm in November has voted resigned since the announcement.
The contradictions of science and the highly public debate about the approval of Aduhelm do not seem to have slowed the enthusiasm in the pharmaceutical industry. Rather, it could signal a new wave of additional treatments in the next few years that will piggyback from Aduhelm’s approval (as controversial as this approval may be).
“This is great news for investors and for pharmaceutical companies working on new drugs,” says Alison Ward, Research Associate at the USC Schaeffer Center for Health Policy and Economics.
Historically, there have been a number of factors that made developing an Alzheimer’s drug an uphill battle.
The first is a 17 year history of failing to get a drug through clinical trials. Even Biogen’s clinical trials for Aduhelm were halted in 2019 because it was not clear that they would meet their clinical endpoints (effectively, the trial’s target results). In fact, Aduhlem was approved based on a “surrogate endpoint,” beta amyloid decline, not the primary endpoint, cognitive function.
Studies with Alzheimer’s drugs have also been expensive in the past. A paper from 2018 in Alzheimer’s and Dementia: Translational Research and Clinical Interventions (a journal of the Alzheimer’s Association) estimated the cost of developing an Alzheimer’s drug to be around $ 5.6 billion. In comparison, the average investment required to bring a new drug to market is around $ 1.3 billion according to an analysis of SEC filings for companies that filed for FDA approval between 2009 and 2018 (though the average cost was about $ 985 million). Older estimates put the cost of getting a drug to market $ 2.8 billion.
For Alzheimer’s disease in particular, Phase 3 trials are still largely industry sponsored, but for the past five years only industry sponsored trials have been decreased. Government grants and funding through public-private partnerships have an iincreasing proportion of available funds.
Martin Tolar, the founder CEO of AlzeonAnother company targeting the oral treatment of Alzheimer’s (currently in a Phase 3 clinical trial) says it was challenging to find other forms of funding.
“It was impossible to fund anything,” he says. “It was impossible to get Wall Street interested because everything failed one by one.”
He expects this recent approval of Aduhelm to change that outlook significantly. We are already seeing increased interest in companies that are already in Phase 3 clinical trials, following the FDA’s announcement Shares in Eli Lillywho is also conducting a phase 3 clinical study, increased by 10 percent.
“I’ve probably had hundreds of conversations, calls from bankers, investors, employees, pharmaceutical companies, whatever,” says Tolar. “Alzheimer’s is open.”
With renewed interest and what looks like a path to FDA approval, the environment for the next generation of Alzheimer’s drugs appears to be maturing. At the moment there is about 130 Phase 3 clinical trials of Alzheimer’s drugs that are either completed, active, or recruiting.
Tolar sees the FDA’s decision, which is based on imperfect data, as a “signal of urgency” to approve new treatments that are immediately on the market.
As Ward in a. stressed White paper When it comes to in-class drug innovation, “follow-on” drugs become industry leaders, especially if they are more safe or effective than the drug that first hit the market. This suggests that drug approval could pave the way for more effective drugs in the future.
In the case of Alzheimer’s, one drug may not dominate even if more are approved, she notes. Rather, a cadre of new, approved drugs can complement each other.
“The way the medical community thinks about AD [Alzheimer’s Disease] Now it is likely that a combination of drugs or a cocktail of drugs will come together to have real success in delaying progression, ”she says.
“If we want to treat AD with a drug cocktail, history suggests that these are individually approved drugs that come together to make these drug cocktails.”
There are still some potential pitfalls to consider for future drugs. One argument is that an approved drug can make it more difficult to recruit participants for clinical trials, slowing the pace of drug discovery. In that regard, Ward argues that this will ultimately be dwarfed by patients who are now investigating a possible diagnosis for Alzheimer’s because there is something that can be used to treat it.
In addition, the costs of Aduhelm are high (approx $ 56,000 for an annual supply, the main thing of which will be supported by Medicare) and the data remains questionable. These factors can push patients to other medications even when they are in clinical trials.
Additionally, how well does Aduhelm actually perform during the critical follow-up study mandated by the FDA as a condition for approval of the drug? Whether Aduhelm can really slow down cognitive decline and help fight beta-amyloid levels from the brain remains questionable based on current data.
However, Tolar doesn’t see the results of this study as particularly relevant as the industry will have moved on. Biogen CEO Michel Vounatsos has said the results of this study may not be announced to as many as nine years, although he noted that the company would try to deliver data sooner.
“By then there will be better drugs,” predicts Tolar.
Tolar’s Phase 3 clinical trial just started and is scheduled to begin dosing this week End of 2024.
Biogen and Esai likely will Likewise have another drug ready for evaluation by then as two Phase 3 clinical trials of another beta-amyloid antibody treatment called lecanemab are due to be completed until 2024 and 2027.
The signal sent by the approval on Monday could be a path for future drugs more than an end in itself. The data is imperfect, the cost is high and the controversy is considerable, but the patch is ripped off.