The study, “Nusinersen treatment of spinal muscular atrophy: current knowledge and existing gaps,” was published in the journal Developmental Medicine & Child Neurology.
Spinraza — developed by Biogen to increase the expression of SMN, the protein lacking in SMA — is the first approved therapy for treating pediatric and adult patients with SMA. It is currently approved in the U.S., the European Union, Switzerland, Canada, Australia, Brazil, Japan, South Korea, and Chile, and reimbursed in the U.S. and several European countries.
Two specialists in neuromuscular diseases working in Paris reviewed the therapeutic benefits of Spinraza for the several types of SMA, as well as identifying questions that still need to be answered related to its use.
Most clinical studies of Spinraza in SMA have been conducted in patients with SMA type 1, the most common and second most severe form of the disease. Phase 3 studies have shown that Spinraza leads to significant clinical improvements in patients with SMA type 1 or type 2 — the intermediate form.
The effectiveness of Spinraza has been, or is being evaluated, not only in patients who are already symptomatic but also those who are not yet exhibiting symptoms. The Phase 2 NURTURE study (NCT02386553), for example, is assessing the therapy’s effectiveness and safety compared with the disease’s natural course. So far, the trial has shown promising results, with a preliminary analysis earlier this year showing that, at the time, all 25 presymptomatic infants treated did not require permanent ventilation and exhibited motor improvements.
Before its approval, Spinraza was provided to patients with type 1 SMA through an Expanded Access Program (EAP). So far, experiences with the treatment — most of which were positive in terms of clinical outcomes — from four different countries have been published: Germany, Italy, France and Australia. An EAP is currently open in New Zealand; Spinraza will soon be commercially available in Australia; and the treatment price is currently being negotiated in Canada.
Although a large amount of data has been generated over the past five years, researchers noted there are still several knowledge gaps regarding the use of Spinraza in SMA.
So far, no data has been published on the potential therapeutic effects of Spinraza in patients with SMA type 0 (prenatal SMA), the most severe form, or with SMA type 4 (adult-onset SMA), the least severe form.
Results on the effectiveness of Spinraza in patients with SMA type 3 — a milder form of the disease — are also limited, with only preliminary (and unpublished) results showing a continued improvement with Spinraza over a three-year period.
In addition, long-term results on the therapeutic effects of Spinraza in presymptomatic and SMA type 1 patients are lacking. The Phase 3 SHINE study (NCT02594124) — following patients who had previously participated in a Spinraza clinical study — as well as national and international registries, are expected to add some knowledge to its long-term effects in patients with SMA type 1.
According to the physicians, further studies are also required to: understand whether the SMN protein is important in other tissues besides the central nervous system (brain and spinal cord); identify biomarkers that would help distinguish between patients most likely to respond to Spinraza and those who won’t; evaluate Spinraza’s benefits in patients with a permanent need for ventilation; develop strategies to administer Spinraza to patients with severe spinal deformations and to evaluate its therapeutic benefits in these patients; and assess the potential use of other therapies in combination with Spinraza.
Regarding Spinraza’s costs, the authors believe that “early identification of good responders through multiple sensitive outcome measures and optimizing the drug efficacy by treating patients before symptom onset through screening of newborn infants could decrease the cost burden of this innovative medication.”
They concluded that while Spinraza is an example of a successful transition from preclinical evidence to its approved use in the clinic, there is still a lot to understand about its use in the different types of SMA.