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House lawmakers urged the FDA to be more flexible in reviewing potential therapies for amyotrophic lateral sclerosis (ALS), and other neurodegenerative diseases, during a hearing of the on Thursday.

Members also stressed the need to increase diversity in and improve access to clinical trials.

Each year, 50 million people suffer from neurological disease such as ALS, Alzheimer's disease, Huntington's disease, and Parkinson's disease, said Subcommittee Chairwoman Anna Eshoo (D-Calif.). Despite the overwhelming prevalence of these disorders, there are few effective treatments available.

"Lack of investment, difficult drug approval processes, and limited understanding of these extremely heterogeneous diseases all keep effective drugs off the market," she said.

There have been "breakthroughs" that have helped scientist understand the genetic basis for some of these disorders and even identify potential biomarkers, "but this has yet to translate into effective treatments," said Eshoo.

"For patients, a diagnosis is still a death sentence," she said.

One way Congress has tried to help was by boosting funding for the FDA, with an increase in the agency's budget of nearly $250 million for fiscal year 2022, she said.

Eshoo pressed witnesses to offer their recommendations for how Congress can help support the FDA's mission of bringing safe and effective drugs to market.

ALS Patients Losing Hope

Several members of the committee spoke about the frustrations of the ALS community in accessing potential therapies.

In 2019, the FDA released guidance for drug developers producing treatments for ALS, a progressive neurodegenerative disease that causes damage to the brain and the spinal cord and carries a prognosis of roughly 3 to 5 years.

But the agency recently rejected two therapies for the disease, said Rep. G. K. Butterfield (D-N.C.). One "promising therapy" -- AMX0035 -- was rejected despite demonstrating that it slowed disability by 30% and extended survival by 6 months "for a subset of patients," he noted.

Butterfield said he believed the treatment was rejected because the agency would have required a 3- to 4-year "confirmatory trial," during which time 20,000 current ALS patients would have died.

The FDA has shown some leniency in offering emergency use authorization in other areas, he said, so "why hasn't FDA employed this flexibility for ALS treatment?"

Patrizia Cavazzoni, MD, director of the FDA's Center for Drug Evaluation and Research, said the agency has consistently followed its guidance, which recognizes a higher threshold of risk for patients with disorders where there is an unmet need for treatment, and acknowledges the need "to accept some degree of uncertainty around the benefits."

Rep. John Joyce, MD (R-Pa.), said he's also heard criticism from the ALS community regarding the agency's inability to exercise "regulatory flexibility," and asked Cavazzoni whether she felt the current ALS guidance was "reliable."

She said the guidance indeed plays an important role.

But "at the end of the day we have to make decisions on the basis of the strength of the data," and while there have been clinical trials that closely followed the agency's guidance, "sometimes we are disappointed by what the clinical trials give us in terms of results, and we're left with data that are sometimes either very complex to understand, or sometimes insufficient for us to make a determination that the drug can be approved," said Cavazzoni.

Patients 'Self-Experimenting,' Expanded Access

Members also asked witnesses what is being done to increase access for patients to experimental therapies through clinical trials and by other means.

Butterfield cited the example of a director of one Duke University clinic in his area who said he had treated nearly 3,000 ALS patients in his career, most of whom could not access a clinical trial.

Some of the director's patients have, out of desperation, begun "self-experimenting" with treatments they found online.

Butterfield said he knows that the FDA can't order a company to provide patients with a drug through "expanded access" protocols -- sometimes called "compassionate use" -- but he asked whether the agency could incentivize drug developers to do so.

Cavazzoni said there have been instances where the agency has tried repeatedly to get a drug company to offer a therapy under expanded access, without success. One thing the FDA has done to try to accelerate drug development is to not require sponsors to establish as large of a safety database for expanded access programs as they normally would.

Increasing Diversity in Clinical Trials

Rep. Lisa Blunt Rochester (D-Del.) also raised concerns about patients access to clinical trials, particularly, patients of color.

Black Americans are twice as likely to develop Alzheimer's disease and Latino Americans are 1.5 times more likely to develop the disease than non-Latino white Americans and yet, Latino and Black Americans account for only 10% of clinical trial participants.

The National Institutes on Aging (NIA) at NIH funds 31 Alzheimer's Disease Research Centers, she said, but many are situated in the "most wealthy" neighborhoods.

NIA Director Richard Hodes, MD, earlier in the hearing noted that the NIH in "previously unrepresented areas" to include Nevada, New Mexico, Alabama, and Tennessee.

He agreed that often sites are located in academic research centers in large cities, which can be a limitation for many patients. The NIH is, however, leveraging technology to allow remote contact with patients and to conduct cognitive assessments, he said.

Hodes said he's also looking forward to being able to put in place real-time registries to track the volume of patients in a study along with demographics, and then quickly intervene if study data show the demographics are not meeting the agency's standards.

Cavazzoni said the FDA encourages developers to expand their recruitment for clinical trials by establishing a network of treating physicians who can refer participants from underserved and rural areas.

But it can be challenging for patients with debilitating diseases to travel long distances to a site, she noted.

To that end, the FDA also urges developers to leverage tools such as "decentralized clinical trials" -- studies that use telehealth to conduct procedures remotely, when possible. The agency issued guidance around these types of trial designs during the COVID-19 pandemic and is working on on decentralized clinical trials going forward.

"We think that we can get to a point where we can have greater representation, and appropriate representation of all the subgroups, while not slowing down drug development and the timing of clinical trials," Cavazzoni said.

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