The work of healthcare communications professionals often involves facilitating patients’ access to medicines. In a cruel twist, one of this industry’s own has found herself fighting for that very same access.
This week, Lisa Stockman-Mauriello, a 30-year agency veteran who’s enjoyed a very successful career in pharmaceutical communications, encountered a setback in that struggle, when Biogen stood by its earlier refusal of a request — made through her physician — for compassionate use of the biotech’s experimental medicine tofersen. The drug is currently undergoing late-stage testing as a treatment for a genetic form of the disease amyotrophic lateral sclerosis (ALS).
Stockman-Mauriello suffers from that exact form of ALS, known as SOD1-ALS, and has been pleading with Biogen for early access to the drug. Her physician, who is among the tofersen trial investigators, believes the drug may help her to stave off the disease’s typically rapid progression long enough to see her three sons achieve some important life milestones.
Unfortunately, she was diagnosed just after enrollment had closed in the biotech’s placebo-controlled clinical trial, and Biogen has so far rebuffed those attempts to gain access to the investigational therapy.
“Offering tofersen outside of the study would risk failing to complete the study and risk failing to obtain access for all SOD1-ALS patients,” wrote Alfred Sandrock, EVP of research & development for the company, in a letter posted to its site Wednesday.
Indeed, such access could scuttle the trial, as some of the study subjects might then demand to know whether they’re in the placebo arm (or be able to tell on their own, based on disease progression). If they’re in the placebo arm, some may decide that, because efficacy is as yet undetermined, it’s not worth the possible side effects to move to the treatment arm.
Still others might demand the drug and drop out of the control group — a situation known as “contamination” — and alter the size of the cohorts.
“Biogen is clearly looking at this as a threat to retaining patients in their trials,” noted Ken Kaitin, who directs the Center for the Study of Drug Development at Tufts University School of Medicine.
“This issue came up a lot during the AIDS epidemic,” Kaitin recalled. “Often, companies developing AIDS drugs were under tremendous pressure to provide their treatments as compassionate INDs [investigational new drugs], so patients could get access to them. But at the same time, the company and some of those patients were aware that this could slow up approval of an AIDS drug.”
Just like during that earlier period, he added, “If a patient knew they could get access through compassionate use, why in the world would they sign up for a clinical trial?” – or, for those already enrolled, stay in the trial at all?
“Recruiting patients for trials is a very difficult thing,” Kaitin explained. “It’s time-consuming, expensive, leads to delays and that can increase costs. Companies do all they can to recruit and retain their subjects, and don’t want to do anything that may jeopardize retention.”
Assuming the study continues to the end, any dropouts from the cohorts could potentially preclude researchers’ ability to discern statistical differences between the groups. That could undermine the trial’s ability to show whether or not the medicine is effective. And that would be a tragedy, because tofersen might be an effective drug, but if its efficacy cannot be observed, the drug may fall by the wayside and the ALS community might never find out for sure.
In another cruel twist of fate, the FDA might reject it for lack of efficacy, cutting off supply to existing patients, including Stockman-Mauriello (if she were to gain access) – and potentially her own children, if they were to be carriers of the same genetic mutation as their mother and end up battling the illness.
Biogen, which has seen other confirmatory trials of once-promising ALS drugs fail, knows the risks all too well.
“These patients agreed to participate in our study acknowledging the risk that they may not receive tofersen, and with hope that tofersen could be shown to work and be approved for all patients,” Sandrock added. “We cannot overlook these patients when considering questions of broader access, and cannot keep them on placebo while at the same time offering tofersen to those outside of our study.”
Not surprisingly, Stockman-Mauriello disagreed with that decision. In a response letter posted to her Facebook group, she acknowledged the challenges and said she respects the company and patients participating in the trial, but wrote that “the company is wrong in concluding that the only option available is to ‘open the floodgates’ to the active drug. That simply is not based in either science or humanity, the two tenets that Biogen claims are at the core of its mission.”
Given the average life expectancy for patients with ALS is thought to be between two and five years (but shorter for those with the rare SOD1 gene mutation), “the implications of Biogen’s reasoning are breathtaking,” she continued. “It sacrifices an entire generation of the community while a decades-old approach to clinical research runs its course.”
Whichever way one nets out on the ethical considerations, it doesn’t lessen the seriousness of her plight, nor collective sympathy for her cause.
“If I were the family of this woman — or this woman herself — I would be outraged, upset,” said Kaitin. “But looking at it dispassionately, you have to view the way Biogen is considering this, and the greater good may be served by getting through this clinical trial.”
Indeed, Biogen clearly sees this as a tradeoff — serve individual patients or society at large — and in this case, it appears the firm has decided on the latter course.
If the trial, which is due to read out later this year, were to be positive and show a favorable benefit-risk profile, without further need for controlled clinical trials, Biogen is prepared to immediately open an early access to tofersen for people with SOD1-ALS, Sandrock added.
Stockman-Mauriello, though, may not have the luxury of time, a harsh reality which she and her family are well aware. She argued that finding a long-term solution to help patients like her would also benefit society at large.
And while it may not be enough to sway Biogen, many of Stockman-Mauriello’s peers have her back — an online petition making her case for compassionate use garnered more than 90,000 signatures.
Her supporters hope that Biogen’s latest refusal is but a temporary setback, and that this consummate industry insider — who once directed launch efforts for an Alzheimer’s drug earlier in her career — may no longer find herself on the outside.