When faced with a loved one’s progressive neurodegenerative disease, like Alzheimer’s, or your child’s rare respiratory disease, you question why researchers and resource-backed pharma cannot bring a drug to market quickly enough to help your loved ones. Many people faced with this horror get involved to fight for better treatments.
The voices of patients and loved ones may have influenced the FDA’s decision to grant expedited approval to two Alzheimer’s drugs, lecanemab and aducanumab. Though aducanumab failed its clinical trials, patient advocacy groups spent significant resources writing letters, working with celebrities, and speaking at advisory committee sessions, aiming to convince the FDA to approve the drug, which it ultimately did.
The story of lecanemab is different. The drug met its endpoints in a single pivotal clinical trial. However, most drugs go through multiple trials to ensure efficacy, which is exactly what the authors of the study recommended. Before the FDA made a decision, patient advocacy groups gathered to advocate for its accelerated approval. And before the expected decision for full FDA approval, again, patient advocacy groups wrote letters and spoke up at the advisory committee meeting.
While it’s impossible to determine how much these efforts influenced the approvals, it’s clear patient advocacy played a role. In the case of aducanumab, the Office of New Drugs Director Peter Stein even confirmed this during a press conference. He said the FDA “heard very clearly from patients that they’re willing to accept some uncertainty to have access to a drug that could provide meaningful benefit in preventing the progression of this disease, which, as we all know, can have very devastating consequences.”
I also know from my experience working in pharmaceuticals that when patient groups showed up, staff were motivated to move budgets around and move research forward faster. I believe this sentiment similarly applies to the FDA when patient advocacy groups speak at advisory committee meetings.
It’s easy to join the loudest voices when the heart of the matter is in your throat. Patient advocacy groups are built of good people with good intentions and great loss. Many patients and family members of patients involved in patient advocacy groups know that the odds of getting an approved therapy across the line for their specific progressive disease in time is unlikely. The selflessness of their intentions is moving.
Unfortunately, I am conflicted when it comes to how patient advocacy groups direct their resources. I have felt the pain of watching someone slip away before my eyes: I lost my own grandfather to Alzheimer’s. My co-founder traveled the country with her father after he was diagnosed with frontotemporal dementia, looking for possible treatments and finding none. Both of us were deeply compelled to find a better way to advance treatments for rare, untreatable diseases, and we understand the calling to do so.
But the current state of patient advocacy needs reform so that the best, safest drugs come to market. The structure of patient advocacy groups and the haphazard manner in which they wield their immense power are problematic. However, there is an opportunity to positively redirect these efforts for better patient outcomes.
The advancement of science relies on evidential rigor. This is something we risk when we approve therapies that overrely on anecdotal evidence or small-scale studies and under-evaluate the uncertain long-term consequences of the therapies.
Diving back into the circumstances behind the two drugs developed to reduce beta-amyloid plaques: In 2019, two late-stage clinical trials of aducanumab were terminated after a committee determined the drug didn’t demonstrate statistical significance on efficacy in slowing cognitive decline. In one study, the drug slowed cognitive impairment by 22% in a subset of patients, and in a second study there was no benefit compared with the control group. And yet, because this was the first new treatment for Alzheimer’s in more than 18 years, patient advocacy groups were desperate to ensure it would be available to those suffering from the disease. After a largely negative FDA advisory committee meeting in November 2020, where they voted not to recommend aducanumab for approval, patient advocacy groups held a listening session in January 2021, which included testimonials from six patients and two caregivers about their experience with Alzheimer’s and dementia. The group also shared their opinions on how much risk they would tolerate, whether they would take a treatment with limited benefits and the value they placed on a treatment that could slow disease progression or extend their lives.
The FDA’s surprise decision in June 2021 to grant aducanumab accelerated approval in 2021 was celebrated by patient advocacy groups and was questioned by medical experts. Because of the lack of evidence, the Medicare program decided to only cover aducanumab for patients enrolled in a clinical trial.
On the other hand, when Eisai and Biogen were seeking approval for lecanemab, there was what seemed like compelling data from a pivotal study, paid for by Eisai. The study of nearly 1,800 people in the early stages of Alzheimer’s showed those who took the drug had 27% less decline in memory and thinking. Though the authors concluded that “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” a second study wasn’t conducted.
Though aducanumab was already on the market, it wasn’t reaching many patients due to questionable efficacy, Medicare’s lack of coverage, and the drug’s hefty price tag. So again, patient advocacy groups lobbied for lecanemab despite only having results from a single pivotal study instead of two — a rarity in drugs up for FDA approval. This study, however, proved to be enough for the FDA to grant accelerated approval in early 2023. Ahead of the anticipated FDA decision for full approval of the drug, patient advocacy groups again wrote and promoted a letter signed by six of the most influential organizations. Full approval followed a few months later. Whether patients outside of clinical trials will see the benefits of the drug in their day-to-day lives is still to be determined.
The examples underscore how patient advocacy groups — understandably — try to influence decision-makers to bring these drugs to market. Through letters to the FDA, targeted advertisements, appearances at advisory committee meetings, email campaigns, engagement with celebrities, meetings with Congress, and more, patient advocacy groups spend significant time and money to influence the FDA. Whether these drugs are approved due to the efforts of patient advocacy groups, lobbyists, politicians, or other outside factors, the problem remains the same. When we make decisions that lack the necessary scientific rigor to establish robust conclusions, nobody wins. Further, as was the case with both treatments for Alzheimer’s, reliance on such evidence can set a dangerous precedent, lead to biased outcomes, and hinder scientific progress.
The absence of functional evidence in recent drug approvals emphasizes the need for more robust and clinically meaningful outcomes. These concerns extend to various medical conditions, including ALS, Duchenne muscular dystrophy, cystic fibrosis, and other rare diseases. We must consider the next generation of patients and ensure that the therapies available to them aren’t toxic, expensive, and ineffective. When the argument is that treatment must be approved since none are available, what will be the impetus to speedily get the second therapy, which could be entirely more effective, across the line?
Some proponents of these drug approvals say that as long as the drugs are safe, patients should have the option to choose to take the drug. This feels wrong as we’re giving patients the choice to pay for a drug like lecanemab that costs upward of $26,500 annually and may have only minute impacts on the decline of the patient’s neurodegeneration. What family member wouldn’t do everything they could to obtain that approved therapy?
My proposal is not to give up or shutter these groups. The people who build patient advocacy groups are resilient in a way that few are before they firsthand witness the devastation of untreatable disease. The combined power of these groups can move mountains. But their goal should be to work with the medical industry to identify the mountains that, when moved, will have the most positive impacts on patients.
First, I suggest that we shift the focus of patient advocacy groups from testifying in front of FDA advisory panels with anecdotal evidence about why we need to advance a therapy to testifying for increased funding for our research programs in front of Congress. Speaking with NIH, or even large pharmaceutical companies, about the disease patients have can positively change the course of funding around research and drug development, particularly as it pertains to basic research.
Second, people considering joining a patient advocacy group should consider other ways to engage with health care and biotech startups. The scrappiness and dedication of people who work at these companies fit well with the attitudes of potential patient advocacy group members. Startups move nimbly and can quickly bring solutions, ideas, and technology to bigger biotech and pharma companies through partnerships. Large startups often hold lunchtime listening sessions to understand the biggest areas of unmet need, barriers of existing treatments, the total cost of disease (not just money, but time, emotional drain, etc.), and the most impactful clinical endpoints. The goal is to help startups understand the impact of disease on human lives so the companies can adjust their work to ensure they are moving forward meaningful outcomes for patients. These are arenas for significant innovation, and patients and their loved ones can bring their perspectives to these teams to amplify their work.
To build on that point, all health care and biotech startups, regardless of size or stage, must make it a priority to bring in patient voices, whether through listening sessions, a webpage dedicated to collecting feedback, patient surveys, attending patient conferences, or other means. We can’t put the onus solely on the patient to advocate for themselves when our end goal is to make treatments that will improve their lives.
Third, those who do join patient advocacy groups should help researchers — at startups and beyond — identify clinically relevant questions. Anyone working in this industry must be meeting with patients who are afflicted by the diseases they’re focused on. If a drug doesn’t actually help to improve a patient’s day-to-day life and function, what is the point? Patient advocacy groups are the best resource to help researchers understand what questions they need to calibrate toward creating meaningful drugs. Interacting directly with patients keeps researchers honest — is this drug actually going to impact the life of the patient I met? — and focused, as they know what they’re working toward.
To this end, these groups can help with determining the right endpoints for clinical trials. Improving endpoint selection is a huge focus for rare and untreatable disease researchers. Having a patient-centric way to shape the selection of endpoints can greatly impact the success and strength of drugs.
Ultimately, the people that make up patient advocacy groups have good intentions. In another life, I could have been drawn to their work through my own experiences with rare disease. But I worry passion is getting in the way of the critical evaluation that’s necessary to ensure resources are being used most effectively. The strength and power of anyone who is able to work toward tangible change when faced with a seemingly futile situation and immense pain and heartbreak are significant. With a reevaluation of patient advocacy, we can redirect this strength through more effective avenues to tenfold positive outcomes for patients.
Jon Hu is CEO and co-founder of Pepper Bio.