Recent drug approvals have shone a light on the role that patient advocacy groups can play in the regulatory process—but some experts have questions about the ethics of this influence.
Pictured: A patient consults with a doctor/iStock, Artit_fizkes
Patient advocacy organizations have long been influential in the drug development landscape. Most recently, they have played a larger role in the regulatory space, and advisory committee meetings are a prime opportunity for patients to have a say in the drug approval process. But recent approvals—particularly in the neurogenerative and neuromuscular spaces—have ignited a debate among experts about the ethics of this influence and a call for greater transparency.
In the 1980s and 1990s, patient advocacy organizations (PAOs) were instrumental in healthcare policy, campaigning for the approval of HIV drugs and facilitating the passage of the Accelerated Approval pathway.
“Patient advocacy organizations were crucial to the passage of the legislation related to accelerated approval,” Genevieve Kanter, associate professor of public policy at the University of Southern California (USC) Price School of Public Policy, told BioSpace. Today, “to the extent that they have influence, it’s directly on the FDA and its advisory committees.”
With the advisory committee (adcomm) meeting for BrainStorm Cell Therapeutics’ investigational ALS therapy NurOwn on the FDA’s docket this week, this reality is front and center—and with it, some of the most vocal PAOs.
The patient groups’ sway, coupled with the relationships many of them have with drug developers, has led some experts to question the ethics of this influence. But patient advocates themselves say their voices are essential to the regulatory process and that industry funding has no bearing on their ability to represent people affected by disease.
Three Pathways of Influence
Kanter said there are three pathways through which PAOs can exert influence, two of which involve adcomm meetings. The first is the public comment section, which is one way that patients’ opinions are formally incorporated into deliberations.
For Nicole Cimbura, co-lead for the legislative affairs team at I AM ALS, the role of PAOs is to educate decision-makers and the public by encouraging members to submit comments to adcomms and increasing awareness around the disease. “I did not realize until I got into this . . . that some people that are sitting on the Cellular, Tissues and Gene Therapies Advisory Committee [CTGTAC] may not realize that ALS is still 100% fatal,” Cimbura, who lost her husband Mike to the neurodegenerative disease in 2019, told BioSpace. As of Sept. 22, more than 1,800 comments had been submitted for the upcoming NurOwn adcomm.
The second pathway, Kanter said, is the presence of a patient representative on advisory committees. Every adcomm has a patient representative, “and this representative is always a voting member,” she said. On this point, Kanter questions the level of influence such a member might have on their peers. “Unlike the other members, who have to meet some level of technical expertise to be on the committee, there’s no such requirement for patient representatives.” Kanter’s team at USC is researching the extent to which patient representatives’ votes are aligned with those of other committee members.
But Fred Fisher, president of ALS Golden West—formerly the ALS Association’s Golden West Chapter—said that patients know better than anyone whether or not they are being helped by a drug.
“When you take the patient experience and you combine it with data that supports the efficacy of the drug, then it seems an appropriate way to go forward,” he told BioSpace. While patients understandably want earlier access to potentially efficacious drugs, Fisher said it is his responsibility as the head of ALS Golden West to understand the data connected to any drug being considered for approval and to inform the patient community on its worthiness for approval.
The third pathway, Kanter said, is one where PAOs could exert pressure directly on the FDA, a notion she called “conceivable.”
In April 2021, for example, the FDA requested that Amylyx conduct a larger, Phase III trial before filing for approval of the investigational ALS drug Relyvrio—then known as AMX0035. But two months after I AM ALS co-founder Brian Wallach called for and received a congressional hearing, the regulator reversed course and allowed the Cambridge, Mass.–based company to file a New Drug Application. Relyvrio was approved in September 2022, after not one, but an unprecedented two adcomm meetings.
“I believe that patient advocacy groups, like I AM ALS, should work with the FDA to ensure that it is applying the correct standard of review for the approval of a new drug,” Wallach told BioSpace in an email. “To be clear, I do not think that advocacy groups should pressure the FDA to lower their standards for approval.”
While there was significant public pressure on the FDA in regard to the regulatory process for AMX0035, Wallach said that I AM ALS “played no role in securing the second adcomm for Relyvrio. That was a decision made entirely by the FDA.”
Kanter agreed that the FDA appears to be sensitive to public sentiment around particular drugs and offered Sarepta Therapeutics’ Elevidys—which won accelerated approval in June for a narrow segment of patients with Duchenne muscular dystrophy—as an example.
Indeed, when FDA staff were leaning toward rejecting Elevidys, Center for Biologics Evaluation and Research (CBER) Director Peter Marks stepped in and directed officials to convene a meeting of the CTGTAC to consider whether it should be approved, STAT News reported.
But in an email to BioSpace, Marks called this an inaccurate characterization of the underlying circumstances associated with the decision. During the evaluation process, “questions potentially benefitting from expert scientific advice were identified,” Marks said. “As such, a determination was made that input from the agency’s CTGTAC would be beneficial for this evaluation.”
In a more glaring disagreement, the FDA in 2021 approved Biogen’s Aduhelm as the first new Alzheimer’s medicine in more than 18 years—after the Peripheral and Central Nervous System Drugs Advisory Committee voted overwhelmingly against the drug. Three members of the committee resigned in protest. In an opinion published by the New York Times, one of those members, Harvard Professor of Medicine Aaron Kesselheim, along with co-author Jerry Avorn, pointed to the role of PAOs, saying, “In recent years, under steady pressure from the pharmaceutical industry and the patient groups it funds, the FDA has progressively lowered its standards.”
Financial Optics
As Kesselheim and Avorn suggested, funding is at the heart of the debate over the role of PAOs. A 2017 New England Journal of Medicine study found that of the 104 largest U.S.-based patient-advocacy organizations, 86 received money from biopharma and drug device companies. Just one of the organizations explicitly indicated it did not receive industry support, according to NEJM.
Numbers such as these have led many experts, including Kanter, to question whether there could be a conflict of interest present. “It’s a big concern,” she said. “Many, many advocacy groups, especially in the ALS, Alzheimer’s [and] neuromuscular space, do get a lot of their funding” from industry. Advocacy groups are not required to publicly report their funding information, she said, so actual dollar amounts are unknown. Kanter’s team is working to get better data in this area. Based on a cursory review, she said that “almost all of [the Alzheimer’s advocacy groups] have received money from companies with a drug under review or in the pipeline, and many of them are very vocal about their support for accelerated approval, early access to these drugs.”
Fisher said that ALS Golden West does accept donations from biopharma companies and other drug sponsors but that as a percentage of the organization’s total revenue—which is around $10 million per year—these funds are “almost immaterial.” He declined to say how much the industry donations amount to.
Around 27% of the group’s revenue comes from government sources, Fisher said, with individual donors, foundations and corporations—some of whom are in the drug development space—making up the remainder. “So, it would be hard for anyone to make the argument that there’s a conflict of interest because we accept money from companies that are developing drugs or may have a drug in front of the FDA.”
I AM ALS does not accept industry funding, a position CEO Andrea Goodman said is “quite unique” in her experience. In the context of participation in an adcomm, she said she does not believe an organization’s funding status has an effect on the “incredibly authentic and important perspective” its members can share.
“I believe that nonprofit organizations are very capable of having . . . both funding relationships with companies and also [representing] the patient voice in an FDA regulatory conversation,” she told BioSpace, adding that she rejects the idea that industry funding for PAOs is problematic. Goodman said that while these potential conflicts are accepted in the private sector, “when it comes to patient experiences, for some reason, we see them as irrational and conflicted.”
Funding also flows the other way. In a statement outlining its position on NurOwn, the ALS Association said that it partnered with I AM ALS to award BrainStorm $500,000 for a proposal to use biomarkers measurement as part of its Phase III trial.
BrainStorm co-CEO Stacy Lindborg told BioSpace that the grant—along with one from the California Institute for Regenerative Medicine—enabled the company to provide CSF samples to a sample repository for the ALS community to use. “I view that as a very constructive way of ensuring we’re continuing to learn [and support] broader goals,” she said.
Marks told BioSpace that the agency screens advisory committee members and consultants—including voting patient representatives—for financial interests that may create a recusal obligation under federal conflict of interest laws, as well as for other interests and relationships that do not create this obligation but that may create the appearance that member lacks impartiality.
But Kanter said these criteria, which focus on sources of personal income and formal employment, are reasonable for the other types of committee members, but they may not be comprehensive enough for patient representatives. “For example, it seems like the existing criteria would not exclude someone working for a patient advocacy organization that is fully funded by the pharmaceutical industry or funded, say, by the sponsor” of the drug being considered.
Many advocacy groups have significant industry connections apart from or in addition to direct funding: a recently published cross-sectional study showed that of the 50 highest-revenue U.S.-based advocacy groups, 74% had board members with prior or current industry ties, and 50% had paid staff or executives with these ties, according to Medpage Today.
“There are concerns that in addition to industry financial support—which nearly half of PAOs accept—having individuals formerly or currently based in industry serve on PAOs’ boards of directors and as senior leadership may influence PAOs’ priorities, advocacy, and recommendations,” the authors wrote.
A Call for Transparency
Marks said that patient perspectives are “critically important in helping FDA understand the context in which regulatory decisions are made for new drugs and biological products.” Advisory committees, he said, are an “important opportunity” to hear from the public—including patients, patient advocates and caregivers—about the symptoms that matter most to them, the impact of the disease and patients’ experiences with currently available treatments.
For Kanter, the ethical debate boils down to transparency. “The concern is that the selection process for these [patient] representatives is a black box. We—the public—do not know the process behind who gets selected to be a patient representative, the pool from whom these representatives are selected, the organizations that they may be affiliated with and the sources of financial support—especially industry support—of these organizations and these representatives.”
The CTGTAC will convene to discuss BrainStorm’s BLA for NurOwn on Wednesday.
Lindborg said she believes the role of a patient advocacy group should be to advocate for the process. “As a company, we think a key role that advocates can play is to support the regulatory review process, which will allow the agency to do its best work. We believe the adcomm is the right forum to review the clinical evidence supporting NurOwn’s safety and efficacy as an ALS therapy because it provides all the key stakeholders—FDA, independent medical experts, statisticians and patient advocates—with an opportunity to offer their own unique perspective on NurOwn’s clinical dataset as well as the unmet needs of people living with ALS.”
Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn and X @chicat08.
