For a patient with a devastating diagnosis, delaying death can sometimes be the most anyone can hope for. Slowing it enough to make it to one more summer. One more graduation.
Lisa Stockman-Mauriello is a 51 year-old communications expert and mother of three sons. In early January, she was diagnosed with Bulbar Amyotrophic Lateral Sclerosis, a rare and rapidly fatal form of ALS. She knows it would be a long shot to hope for a cure. She just wants to extend her life, something that the promising drug Tofersen, currently being developed by the biotech company Biogen, might help her do. Unfortunately, her diagnosis arrived shortly after Biogen's the deadline passed for the latest phase of its clinical trial recruitment. Stockman-Mauriello asked for an exception to be made. She was turned down. She has since taken her case to the court of public opinion and pressure, via a change.org petition. The petition features a photograph of her, flanked by her dog and holding a sign that reads, "I don't want to die." It currently has over 115,000 signatures.
Over the past few months, Stockman-Mauriello's plight has been covered on major television news shows and news outlets. The reportage has been unambiguously emotional: "Mom Battling Rare ALS Pleads for 'Compassionate Use' of New Life-Saving Drug Biogen Won't Give Her," reads the headline in People magazine. The "Today" show, meanwhile, reported, "Mom with Aggressive ALS Hopes to See Sons Graduate, Asks Drug Company for Help." Stockman-Mauriello's imperative is clear: she doesn't, as she says, want to die.
Biogen's position has also been clear: Stockman-Mauriello was not eligible for the clinical trial. The company's reasoning, however, has been complex, especially to those unfamiliar with the stringent parameters around the clinical research and FDA approval process.
In a public conflict between a sick mom and Big Pharma, the most obvious moral resolution would be to give Stockman-Mauriello access to the drug. But this is not just a story about one person and one heartfelt plea. This has also been about the integrity of a Phase 3 clinical trial and the participants currently enrolled in it, many of whom are on a placebo. It's been about the 15,000 Americans currently living with ALS, and the 5,000 who will be diagnosed with it this year. It's about the ways in which US clinical trials are conducted, and the legal, ethical and scientific questions that surround them. It's about the hope of a more integrative approach to an issue with far-ranging implications.
"Every week, I am rapidly declining from bulbar ALS which is caused by a mutation to my SOD1 gene," Stockman-Mauriello wrote on her change.org page when she started her campaign. "My physician is one of the physicians participating in the trials for Tofersen, and he believes the drug may give me more time. And that is all I am asking for: time. My physician says that he has never seen an ALS case progress as rapidly as mine. I'm losing function every week — but it is not too late — and getting access now can extend my life."
Dr. Neil Schneider, Stockman-Mauriello's doctor and the director of the Eleanor and Lou Gehrig ALS Center at Columbia University's Irving Medical Center, affirmed his position to WRAL News in April, saying, "We are very limited in what we can offer our patients. So this, I feel, is her best chance for a therapeutic that could make a meaningful difference in the course of her disease."
ALS is a uniquely cruel and difficult to treat progressive nervous system disease. The Mayo Clinic notes that "treatments can't reverse the damage of amyotrophic lateral sclerosis, but they can slow the progression of symptoms, prevent complications, and make you more comfortable and independent."
The excitement, then, about Tofersen is understandable. A 2020 report published in the New England Journal of Medicine mere months before Stockman-Mauriello received her life-changing diagnosis indicated that in Phase 1 and 2 of the trial for the drug, it indeed appeared to slow the progression of the disease over a 12-week period.
But it is a tricky and, typically, long road from early trial results to successfully bringing a drug to market. When Operation Warp Speed brought clinical trials into mainstream consciousness, it moved the goalposts for patient communities, who have been advocating for years for accelerated research and development for their own conditions. Expectations and demands have shifted.
"I don't think drug development is ever going to be the same," Alison Bateman-House, assistant professor at New York University's Grossman School of Medicine, told Bloomberg in December. "I think ALS and metastatic breast cancer and other diseases of high unmet need are going to be demanding, 'Where's my Warp Speed?'"
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That results of that demand have been front and center this month, with the FDA approval for Biogen's Alzheimer's drug Aduhelm, the first such new approval for an Alzheimer's drug in 18 years. But there have been strong concerns from the medical community about the effectiveness of the treatment, which will cost patients roughly $56,000 a year. Back in November, an FDA advisory panel expressed its concerns about the drug to the agency, and this week, three FDA advisors resigned in protest.
One of them, neurologist Dr. Joel Perlmutter, stated, "Approval of a drug that is not effective has serious potential to impair future research into new treatments that may be effective. In addition, the implementation of aducanumab therapy will potentially cost billions of dollars, and these dollars may be better spent in either developing better evidence for aducanumab or other therapeutic interventions."
For patients, however, waiting even a few months for something that could offer relief can seem unjust. FiercePharma reports that ever since the drug's approval was announced, doctors' phone lines across the country have been "blowing up" with requests. Aduhelm's blazing path to FDA approval was no doubt helped along by public demand, as well as a strategic, celebrity-backed campaign for "More time."
In 2018, the Right to Try Act was passed with the stated intention of avoiding these kinds of dilemmas. The act promised to assist individuals "who have been diagnosed with life-threatening diseases or conditions who have tried all approved treatment options and who are unable to participate in a clinical trial to access certain unapproved treatments." But the Right to Try Act has been met with harsh criticism from several patient groups, who say it does not address "the primary barriers to access." And trial sponsors still retain the right to decline.
In a March letter to Lisa Stockman-Mauriello, Dr. Maha Radhakrishnan, the Chief Medical Officer of Biogen, informed her that her company decision was just that, explaining: "Until efficacy and safety are determined, we must act with the interests of all patients in mind."
Would it have been fair to offer the drug to Stockman-Mauriello, when others with her condition already participating in the trial are receiving the placebo? Would it have been ethical from a healthcare standpoint, given that the side effects and adverse effects are still being investigated, and Stockman-Mauriello's condition is so precarious? Could Stockman-Mauriello, as she asked, have been enrolled and randomized? Did Biogen do the right thing?
Healthcare and drug development offers endless iterations of the proverbial trolley problem. Who do we save? Or more accurately, who do we attempt to save? The pull of a story like Stockman-Mauriello's is undeniable, especially for those of us who know what it feels like to face a fatal diagnosis, and whose last best shot is an experimental treatment. I do; that is precisely the same abyss I was staring into a decade ago, when I had metastatic melanoma and became one of the first people in the world in a Phase 1 immunotherapy trial.
Likewise, the idea that there might be something, anything out there that could ease the suffering of my mother and my mother-in-law, both of whom have Alzheimer's, makes me want to kick down any door in my path to get to it. Yet the call to empathic and just care must be fair and encompassing. It must consider both the seen and the unseen.
It is not cheap to make or distribute a drug. Resources are not unlimited. The precedent of allowing one person with a compelling plea to gain access to a treatment does not answer the difficult question of what to say to the next person. And the next. And the next and the next.
In a "Community Update" posted on their site earlier this year, Biogen obliquely referenced the Tofersen controversy, stating, "Among the ethical imperatives in any access program are assuring that all patients receive equal treatment and priority and preserving the integrity of ongoing studies…. We do not believe it is fair to ask participants in this study to continue to receive placebo while other SOD1-ALS patients are offered access to Tofersen, but we do believe that access could be provided as soon as the placebo-controlled study has ended."
The tale of a single person's quest for survival is compelling. But as Arthur Caplan, founding head of NYU School of Medicine's Division of Medical Ethics, wrote two years ago for Stat News, "Social media campaigns are inherently unfair in that not everyone is 'mediagenic,' not everyone knows how to mount a campaign, and not everyone draws attention from politicians or the crowdsourcing support often needed to pay for a drug or to travel to get it."
Instead, truly useful solutions involve a top down reframing of the entire process. "The main thing you can do is get more people into clinical trials," says Lisa Kearns, a senior research associate at NYU Grossman School of Medicine's Division of Medical Ethics. "But you have to have an industry that wants to greatly broaden inclusion criteria."
Thanks to factors like limited access, lack of information, complicated requirements for acceptance and blatant historical racism, it's estimated that fewer than 10% of eligible patients enroll in clinical trials, and fewer than 10% of those who do are people of color. The majority of clinical trials don't meet their enrollment requirements, an outrageously costly and time-consuming failure. If we were collectively better at getting people into trials in the first place, we could bring effective treatments to market sooner, and spend a few less billion dollars getting there.
It can happen, by working with patients and advocacy groups, and by creating doctor and patient-friendly resources that give everybody clear information and a fair shot at access, unlike the current mind-numbing, labyrinthine system we have now. Similarly, becoming more sophisticated about acknowledging the demand for expanded access and establishing more space outside of the research for those special cases— as well as widening the parameters of eligibility to develop a more equitable patient population — would reduce the need to issue unpopular decisions regarding the unique cases that will inevitably arise.
Meanwhile, those of us in the media have an obligation to examine and understand the issues we report on, to work harder to interpret complex issues and explore them with nuance and curiosity, especially when a reductive narrative of heroes and villains is so seductive. We are drowning in misinformation, and the COVID-19 crisis has well proven the devastating public health consequences of ignorance.
As for Lisa Stockman-Mauriello, she and Biogen have found some small measure of common ground. Biogen has announced that in July, after the completion of Tofersen's Phase 3 trial, the drug company will be opening up a compassionate use program, which means that ALS patients across the country will be able to apply, via their physicians, for access to the drug. In a June 3 update on her change.org page, Stockman-Mauriello acknowledged the gesture, saying, "That will probably be too late for me, but it will help others with ALS, which is good."