For almost seven years, patients with spinal muscular atrophy (SMA)—a rare disease that in its natural course leads to profound disability and premature death in children, often before the age of two—have had access to treatment. Observations to date indicate that intrathecal therapy administered to patients before symptoms appear can be fully effective, maintaining long-term health without the development of clinical signs. Clinical trials are currently underway on a higher dose of the drug, which may receive European approval at the beginning of the new year.
“Spinal muscular atrophy is a chronic, progressive neurological disease that damages the motor neurons of the spinal cord—the controllers of muscle function. As a result, muscles weaken and atrophy. In more than half of cases, the disease unfortunately has an acute course, beginning in infancy within the first months of life. In over 90% of these patients, it leads to ventilator dependence or death before the age of two,”
says Katarzyna Kotulska-Jóźwiak, Head of the Neurology and Epileptology Clinic at the Children’s Memorial Health Institute (IPCZD), in an interview with Newseria.
In Poland, the B.102 drug programme for SMA patients has been operating since January 2019. The first reimbursed therapy was nusinersen, an oligonucleotide administered into the spinal canal. Even before the programme’s launch, the drug had been provided under early-access schemes. As a result, Poland is among the countries with the longest real-world evidence (RWE) follow-up.
“When we began treating patients with nusinersen, our primary goal was to halt disease progression—to achieve a state in which patients would not deteriorate. About 700 patients are currently treated with this drug within the programme, and nearly 1,000 patients have received it at some stage. More than 97% achieved at least stabilization, and about 80% showed an improvement that we consider clinically meaningful,”
Prof. Kotulska-Jóźwiak emphasizes.
Clinically meaningful improvement is defined as an increase of at least 4 points on the CHOP-INTEND motor function scale—changes that are evident in daily activities, not just laboratory parameters. Analysis of programme data shows that in children with SMA type 1, the average CHOP-INTEND improvement was 5 points after three months and 15 points after 19 months. For patients with SMA types 2 and 3, improvements reached 8.4 and 8.1 points, respectively. The authors note particularly promising outcomes among adult patients with SMA1c, who never achieved independent sitting.
“A figure above 97% is rarely seen in medicine. We almost never deal with a drug that is 100% effective. The small proportion—under 3%—in whom we do not observe effectiveness consists largely of patients who discontinued treatment for various reasons before efficacy could be properly assessed,”
adds the head of the clinic.
As she explains, nusinersen supplies spinal motor neurons with the missing SMN protein necessary for normal motor neuron function. Intrathecal administration targets the site where the disease develops and bypasses the blood–brain barrier, one of the greatest challenges in modern neurology.
“Intrathecal delivery has both advantages and disadvantages. The drawbacks include the burdensome route of administration—it requires lumbar puncture, which can be difficult in patients with scoliosis or those needing general anesthesia. On the other hand, delivering the drug close to motor neurons rather than systemically reduces the risk of adverse effects. When administered intrathecally to patients diagnosed before symptoms, long-term follow-up shows complete effectiveness, meaning patients remain symptom-free,”
Prof. Kotulska-Jóźwiak explains.
Since 2019, the B.102 programme has undergone multiple patient-friendly improvements. All approved therapies are now reimbursed (in addition to nusinersen, onasemnogene abeparvovec and risdiplam). As of 1 April last year, nusinersen may also be administered to pregnant women. The programme allows therapy switching due to permanent or temporary contraindications, intolerance, or loss of efficacy—and recently enabled returning to first-line therapy with nusinersen.
“There remains a need to seek even more effective treatments, and clinical trials are ongoing. We expect the registration of a higher dose of nusinersen in the near future. Until now, only the 12 mg dose was available; we did not know whether a higher dose would be beneficial or safe. The study has just concluded with positive results,”
she says.
“Risdiplam in tablet form is registered and undergoing reimbursement. Trials are also underway for a drug similar to nusinersen but administered once a year, as well as for intrathecal gene therapy, which could be used in older patients [currently, available gene therapy is limited to infants under six months]. Finally, several studies are evaluating adjunctive drugs that do not target the disease’s underlying mechanism but increase muscle contraction strength.”
Experts agree that, beyond broad access to therapy, newborn screening is crucial to the programme’s effectiveness. It enables diagnosis and causal treatment within the first days of life, before symptoms develop. Poland’s SMA treatment programme is widely regarded as a model for Europe.
