When a patient is battling a terminal illness and wants an experimental drug, how much evidence does a regulator need to show it works before approving it?

This is the question behind many of the FDA’s toughest decisions, including last year’s Controversial approval Aduheim. Many experts — including the agency’s own outside advisers — say Alzheimer’s drugs are unlikely to help patients.

Less than a year later, the agency may soon approve another drug for the deadly neurodegenerative disease based on partial data that experts are debating. The FDA meets next week to publicly review evidence from a small mid-stage study of Amylyx Pharmaceuticals’ drug for ALS or amyotrophic lateral sclerosis.

According to the company, regulators told Amylyx last year that it needed to conduct a large confirmatory study before seeking approval. But after months of intense lobbying by ALS patients and their representatives in Congress, the agency said it could submit the drug based on smaller studies.

The change was so sudden that it surprised even some of the doctors who helped research the treatment, which appeared to moderate the decline in patients.

“The effect is there, but it’s not a home run,” said Dr. Jeffrey Rothstein of Johns Hopkins University. “Does it really work? I don’t know. That’s why I’d like to see a second study.”

The FDA has traditionally required two large late-stage studies to gain approval. For a deadly disease like cancer, a study showing promising early results is usually accepted.

Amylyx’s decision was government investigator Investigate Aduhelm’s approval, including whether the agency bowed to pressure from Alzheimer’s groups and pharmaceutical interests.

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Experts studying FDA decisions see disturbing pattern in troubled institution Constant pressure to accept weaker evidence undermines its scientific credibility and opens the door to ineffective treatments.

“In terms of the FDA’s precedent for approval of Aduhelm, that’s what a lot of people worry about,” said Yale University’s Dr. Joseph Ross. “They’re basically bowing to industry and patient advocacy pressure instead of adhering to the science.”

An FDA spokesperson declined to discuss the review, citing agency rules, but noted that Amylyx’s submission “is not a determination on the merits of the application.” The FDA will issue a preliminary review of the drug ahead of Wednesday’s meeting.

There are important differences between the two drugs. The FDA approved the Alzheimer’s drug based on laboratory measurements that showed it helped slow cognitive decline, although company studies failed to show a significant benefit for patients. In the case of Amylyx’s drug, ALS patients showed measurable improvements, but the therapy had no effect on laboratory results.

Given the benefit to patients, advocates argue that the FDA should approve Amylyx’s treatment.

ALS, also known as Lou Gehrig’s disease, destroys the nerve cells needed to walk, speak, swallow and ultimately breathe. There is no cure, and most people die within three to five years.

Amylyx’s drug is a combination of two older pharmaceutical ingredients: a prescription drug for liver disease and a dietary supplement associated with ancient Chinese medicine. Cambridge, Massachusetts-based Amylyx has patented the combination and says the chemicals work together to protect cells from premature death. (Its co-founder declined an interview request for this story.)

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Some ALS patients already take both drugs. FDA approval could force insurers to cover the cost of treatment.

In a study of 137 patients, those taking the drug progressed 25 percent slower than those taking a placebo, according to a 48-point questionnaire that tracked functions such as walking, handwriting and swallowing. The difference in scores (2.3 points) was statistically significant, but experts were divided on its significance for patients.

Dr. Catherine Lomen-Hoerth of the University of California, San Francisco, said even a one-point drop could be significant.

“That’s the difference between being able to feed yourself or not,” said Lomen-Hoerth, who was not involved in the study.

New England Journal of Medicine editorial Call the results “incremental” and “moderate,” and suggest longer, larger studies.

The FDA decision came several years later, but the results sparked a movement in patient groups, starting with petition Call on the agency to take action. When the FDA appeared to change its stance on the drug in September, advocates applauded it.

For people with ALS, the logic is clear: Any drug that prolongs or improves life is worth trying.

The FDA has only approved two treatments for ALS. More effective drugs can extend life by several months, and many experts say Amylyx’s drug may show similar benefits.

“When you’re faced with a choice of nothing, you certainly want the opportunity to try anything that can help you,” said Larry Falivena, who was diagnosed with ALS in 2017. He plans to speak at an event next week. Speaking at an FDA meeting.

The 53-year-old father of two joined six other patients in calling for FDA approval of Amylyx’s drug in an online “listening session” last May.

The conference is organized by the ALS Association, which has invested $2.2 million in Amylyx research.The group – key beneficiary of the 2014 Ice Bucket Challenge viral fundraiser – Potential up to $3.3 million in benefits if the drug is approved.

Such arrangements are standard among nonprofits that fund research, and the proceeds will be used for further research, the association said. In a statement, the group said the payback clause was a way to help “get effective treatments to market as quickly as possible.” It added that it would not advocate approval if the drug was not safe and effective.

During the hearing, the FDA’s Dr. Patrizia Cavazzoni reiterated the agency’s longstanding position: If drugmakers develop better biological measures of drug action, the agency could use them to speed approval.

The 48-point scale used by Amylyx is the standard for ALS research, but some experts question its reliability. For example, it is not uncommon for patients to report functional improvements even as measures such as muscle strength decline.

A few weeks later, Cavazzoni was summoned to a House SubcommitteeDuring a five-hour hearing requested by patient advocates, lawmakers pressed her on the status of the Amylyx drug.

The co-founder of another patient group, I AM ALS, also testified. Brian Wallach and his wife Sandra Abrevaya work in the Obama White House and formed their team after Wallach was diagnosed with ALS in 2017. The nonprofit has quickly become a political force in Washington, pushing Congress to pass legislation that, among other things, requires the FDA to develop a five-year plan to speed up drug development for ALS and similar diseases.

In joint testimony read out by Abrevaya, they called on lawmakers to intervene on behalf of patients: “The answer is simple: let FDA act with the urgency and regulatory flexibility it promises.”

A spokesman for I AM ALS rejected the group’s idea of ??”tell the FDA what to do.”

“We’re not trying to put pressure on the FDA,” Theresa Garner said. “We’re following a standard process, just making sure the FDA and its advisory committees listen to people with this disease.”

The FDA’s external expert advisory group meeting on Wednesday vote against Aduheim. The FDA ignored its recommendations and approved the drug, prompting three members Resign.

Given that the same FDA scientists and leadership are overseeing Amylyx, approval was widely expected.

Rothstein, a researcher at Johns Hopkins University, plans to prescribe the drug to his patients. But he still wants to see more data.

“I hope the FDA waits for two trials,” he said. “The patient will say, ‘You’ve deprived me of a drug.’ The opposite is: ‘I may have deprived you of a drug that didn’t work.'”