The refusal, notified on October 22 by the High Authority for Health (HAS), to grant so-called early access to Qalsody, a drug developed by the American laboratory Biogen to treat a rare form of amyotrophic lateral sclerosis (ALS), is a of these regulatory decisions where the barrier of technical jargon, scientific complexity and procedural subtleties mask the human drama playing out behind.
To understand this, we must listen to Pauline, 22 years old, a patient who fears that this decision by the health authority will tomorrow deprive her of the only treatment available for an illness that today condemns her to the chair and threatens her with progressive paralysis. , to kill her within a few months.
Life expectancy reduced to two or three years
The destiny of the young woman changed on November 17, 2022. “That day, during an appointment at the Pitié-Salpêtrière hospital in Paris, I was told that I had a serious neurodegenerative pathologyshe says. In shock, I didn't quite realize. It was in the evening, while consulting the Internet, that I understood that I was going towards death. »
Specialists speak of “ALS-SOD1”, a rare form of Charcot disease, a name better known to the general public. “It is linked to a mutation in the SOD1 gene which produces a protein toxic to motor neurons,” explains neurologist François Salachas, head of the Île-de-France ALS Reference Center. Hereditary, it affects around a hundred people per year in France. “It results in extensive paralysis with respiratory damage, which is life-threatening two to three years after the onset of symptoms. And there is no treatment,” he specifies.
At least, until the arrival of the Qalsody. Based on the tofersen molecule, this treatment developed by Biogen has promised a lot in recent years. In December 2022, the National Medicines Safety Agency (ANSM) authorized its “compassionate access”an exemption system which allows the prescribing and reimbursement of a medicine for which it is presumed, without having proof, a favorable benefit/risk ratio. This allowed around fifty patients to benefit, including Pauline.
An “unacceptable and incomprehensible” decision
“I had my first injection via lumbar puncture in March 2023 and, since then, I have received one per month. It's painful at the time, but over time, I notice that my illness is stabilized. And that opens up perspectives,” she testifies. Also, when Pauline learned of the HAS's decision, she felt abandoned. “I am sad and angry. For me, that sounds like a death sentence,” she blurted.
Strong words taken up by the Association for Research on ALS (ARSLA) which launched a petition against a decision judged “unacceptable and incomprehensible”. “While theEuropean Medicines Agency gave in February 2024 marketing authorization for this treatment already approved in Germany, Italy and the United States and undeniable results show its effectiveness, the HAS deprives patients of the only concrete hope of slowing the progression of this devastating disease,” laments Sabine Turgeman, director of ARSLA.
A cry of alarm relayed by around twenty deputies who signed a letter to the Head of State. “In addition to the human drama that is playing out, we wanted to alert them to the demobilizing signal that this refusal sends to manufacturers, researchers and caregivers who are involved in rare diseases,” underlines the MP (Renaissance) for Gironde Sophie Panonacle, at the origin of the initiative.
The four criteria for early access
Requested by The Crossthe HAS would like to point out that its mission is “to provide patients with effective treatments. To do this, we respect the rules set by law and a scientifically established methodology. What was done for the Qalsody – tofersen »underlines Floriane Pelon, director of evaluation and access to innovation.
To obtain early access, a treatment must meet four criteria: treat a serious, rare and disabling disease; that there is no appropriate treatment; that it is presumed to be innovative and that its implementation cannot be delayed. However, according to the decision published by the HAS, the Qalsody responds well to the first two but not to the last two.
“Analysis of the results of the phase III trial carried out by Biogen, carried out on 108 patients over six months, demonstrates that this treatment has no significant effect if we compare the clinical state of the patients who received it. 'received and those who received a placebo', summarizes Floriane Pelon. “What we regret”, she adds. But which led the HAS to rule that the medicine was not “likely to fill a medical need”.
Limitations of the evaluation model
While he does not dispute the rigor of the methodology, Dr. Salachas highlights its limits. “The trial conducted by Biogen certainly does not provide definitive proof, but certain elements strongly argue in favor of its effectiveness,” he says. In particular, we note that the SOD1 protein level decreases considerably in patients who received tofersen. And that neurofilaments, biomarkers which attest to the destruction of motor neurons, are also in free fall. “Which is unheard of in a neurodegenerative disease, he enthuses. But one of the problems is the difficulty of integrating this type of innovative results into the evaluation of the effectiveness of certain treatments. »
Likewise, health authorities are still reluctant to take into account the data collected from treated patients when there is no possibility of comparing to a placebo. “Because they consider them too fragile unless the treatment demonstrates a major impact. For them, the exclusive method remains double-blind versus placebo,” adds Doctor Salachas.
An appeal examined on November 20
At the HAS, we refuse to be stuck on an immutable doctrine. “We have set up a working group on early access to better manage uncertainty and refine the assessment of the presumption of innovation criteria,” specifies Floriane Pelon. But this project will take time. What the patients concerned miss most.
For Pauline and the others, it remains to be hoped that the HAS changes its mind. We will know on November 20, the date of the voluntary appeal filed by Biogen during which the laboratory and expert neurologists in the ALS health sector will plead for the body to review its position.
