NIH to fund unproven ALS drugs under patient-backed law

WASHINGTON (AP) — When patients with a deadly diagnosis and few treatment options have tried to obtain unapproved experimental drugs, they have long faced a dilemma: Who will pay?

The responsibility for funding so-called compassionate use has always rested with drugmakers, although many are unwilling or unable to make their drugs available to dying patients for free.

After years of lobbying Congress, patients with the debilitating disease known as Lou Gehrig’s disease have found an unprecedented solution: make the federal government pay.

Under recent legislation, the National Institutes of Health will begin spending about $25 million to enroll patients in programs for the compassionate use — also called open access — of unapproved drugs. The first stage, announced on Friday, will give patients access to a sugar-based injection called trehalose, which is believed to help nerve cells eliminate toxic proteins.

Only patients who cannot participate in conventional drug trials are eligible for the program. And their progress needs to be tracked to gather data on treatment and their underlying disease, amyotrophic lateral sclerosis, or ALS.

The initiative blurs the line between treatment and research, and puts the NIH in the position to pay for unapproved drugs in studies that may yield limited data. While it offers a critical new option for ALS patients, it also raises the possibility that limited federal funds could eventually be tapped for more unproven treatments in other diseases.

“We don’t usually expect the government to pay for things until we know they work,” said Holly Fernandez Lynch, a bioethicist at the University of Pennsylvania. “But the system we have in this country relies on pharmaceutical companies to develop our drugs, and private companies are not there to provide their products for free.”

Fernandez Lynch and many other experts support the new approach as an innovative solution to the challenges faced by ALS patients, who typically survive three to five years after first symptoms. The disease destroys the nerve cells needed to walk, talk and, eventually, breathe.

According to the researchers, up to 90% of patients with ALS are not eligible for traditional clinical trials, usually because their disease has progressed too far to show major treatment benefits. Even eligible patients must compete for access. A recent analysis counted 2,000 trial openings in the United States for 25,000 people living with ALS.

Patients are not the only beneficiaries of the NIH program. Government funding essentially replaces the costs previously borne by drug manufacturers.

A longtime patient advocate sees a troubling precedent in this financial shift.

“My sense is that it’s the responsibility of companies, not taxpayers, to bear the cost of expanded access programs,” said Gregg Gonsalves, a Yale University researcher who advised informally ALS patients on expanded access. “But the companies blocked patients for years, so as a last resort they went to Congress.”

During the 1980s and 1990s, Gonsalves and other HIV activists were instrumental in pushing drugmakers to provide early access to experimental drugs.

ALS patients say most companies in their field are tiny startups that can’t afford such costs. Drugmakers have other reasons for denying access, including concerns that unexpected safety issues could hurt their chances of approval.

The NIH spends the vast majority of its $45 billion budget on early-stage research focused on identifying the root causes, treatments, and potential cures for diseases.

Monitoring medication safety is a key aspect of the new program, along with various biological measures of ALS. But the initiative is unlikely to detect whether the drugs actually work because patients will not be compared to a placebo group, the gold standard approach in medical research.

“Unless the drug is a miracle drug, you’re unlikely to see efficacy in this kind of research,” said Dr. Walter Koroshetz, of the National Institute of Neurological Disorders and Stroke.

The initiative is part of broader legislation passed by Congress last year by patient advocates including I AM ALS, a nonprofit co-founded by two former Obama White House staffers. .

“I’m five, so I can’t qualify for clinical trials,” said Brian Wallach, who started I AM ALS with his wife after being diagnosed in 2017. extended access.”

He describes the new NIH program as a “pilot” that will be reviewed by federal inspectors, as required by the new law.

Wallach spent several years working on the legislation with congressional staffers. It passed the House last year by a vote of 423 to 3, a rare display of bipartisanship that also underscored the group’s political clout.

The sweeping bill requires the Food and Drug Administration to develop a plan to accelerate drug development and form new partnerships to study neurodegenerative diseases.

The legislation arose out of deep patient frustration over access to experimental therapies, including a stem cell treatment from small drugmaker Brainstorm Cell Therapeutics.

After the company’s 200-patient study failed to show positive results in 2020, Brainstorm allowed a handful of patients to continue receiving injections under expanded access. But company executives said a larger program was unfeasible, given that Brainstorm has no revenue.

“We used millions of dollars for our little expanded access program,” said Mary Kay Turner, a company executive. “So we did as much as we could, but it was only a tiny bit.”

Brainstorm plans to submit its drug for FDA approval, despite a rare public statement from the agency last year that the company’s data “does not support the proposed clinical benefit.” This followed thousands of calls and messages to the agency from ALS patients.

Although many treatments may prove ineffective, Dr. Richard Bedlack of Duke University says that getting patients into expanded access programs is still better than the current situation, in which they often seek treatment themselves. untested remedies.

“Historically, their only option was to go online and try to buy these supplements or alternative therapies,” said Bedlack, who consults with multiple drugmakers.

It remains to be seen how many patients the NIH will enroll under its $25 million grant. The original legislation provided funding of $100 million over four years. House lawmakers have budgeted $80 million in spending bills for the next fiscal year, though those have yet to pass the Senate.

For now, NIH’s Koroshetz notes that expanded access studies will be more expensive than other NIH trials because the government bears the cost of manufacturing and distributing the drugs.

He conceded: “It’s a bit different from our usual grants, where we don’t pay the companies for the drug at all.”


Follow Matthew Perrone on Twitter: @AP_FDAwriter


The Associated Press Health and Science Department is supported by the Howard Hughes Medical Institute Department of Science Education. The AP is solely responsible for all content.