Nusinersen at a higher dose. There are the results of the study

The latest results from Part C of the DEVOTE clinical trial, which evaluated a treatment regimen with a higher dose of nusinersen, and the NURTURE clinical trial, which evaluated an approved treatment regimen with a 12 mg dose of nusinersen in patients with presymptomatic SMA, were presented at the SMA Research & Clinical Care Meeting, hosted by Cure SMA and held in Anaheim, California. Biogen's applications for approval of the higher-dose nusinersen treatment regimen are currently under review in the United States, Europe, Japan and other global markets. The higher-dose nusinersen regimen includes faster saturating doses - two 50 mg doses 14 days apart - and higher maintenance doses - 28 mg every four months.

"As the field of SMA therapy continues to evolve, we remain steadfast in our efforts to realistically address the unmet needs of this community. The results of Part C of the DEVOTE study further reinforce the accumulated evidence supporting the potential benefits of higher dose nusinersen." - Stephanie Fradette, PharmD and Director of Drug Development for Neuromuscular Diseases at Biogen, said.

Improvement observed in already treated patient population with higher-dose nusinersen regimen

The detailed results of Part C of the DEVOTE study underscore the potential clinical benefit of the higher dose of nusinersen under investigation in a broad group of people (n=38) who had previously been treated with nusinersen at the approved dose of 12 mg for about four years (median: 3.9 years). Participants' ages ranged from 4 to 65 years, and half of them (n=19) were walking patients. In Part C of the study (a higher-dose open-label trial), participants received one saturating dose (50 mg) and two maintenance doses (28 mg each) of nusinersen.

After switching to the higher-dose regimen, the majority of participants showed improvement in the Hammersmith Expanded Motor Function Scale (HFMSE), the Revised Upper Limb Rating Module (RULM) and/or the Clinical General Impression - Change scale (CGI-C; as assessed by the investigator or caregiver). Improvement effects were observed across all phenotypes, functional states and age groups. For example, non-walking patients showed a mean improvement of +2.5 (CI 95%: 0.49, 4.56) on the HFMSE scale, and walking participants achieved an improvement of +1.1 (CI 95% CI: -0.68, 2.89).

"These latest data indicate that additional functional improvement can occur even in people with established disease who have been treated for many years," - said Dr. Richard Finkel, director of the Center for Experimental Neurotherapy (CENT) at St. Jude Pediatric Clinical Hospital. "Efforts to optimize the dosage of the drug nusinersen are generating enthusiasm and could fundamentally change the way we treat our patients."

The safety profile for the higher-dose nusinersen regimen is generally consistent with the safety profile established for the 12 mg dose. Adverse events (AEs) reported in the DEVOTE trial included pneumonia, respiratory distress, fever, COVID, upper respiratory tract infection, pain, and procedure-related and procedure-related headaches. In Part C (n=40), adverse events were reported in 37/40 participants, most of which were mild to moderate in severity. Serious adverse events were reported in six participants (15%), none of which were considered by the investigator to be related to the study drug or its administration.

Final data from NURTURE study changes expectations for early treatment

Final data from the eight-year open-label NURTURE study show the impact of early intervention with 12 mg of the drug nusinersen in infants with presymptomatic SMA.

At the end of the NURTURE study, all participating children (n=25) were alive, and were reported to have sustained clinical benefit. None of the participants required continuous ventilation, and the majority (20 of 25 participants) did not benefit from any respiratory support during the study. Ninety-two percent of participants achieved the ability to walk independently, including many within a standard developmental framework. Participants who had elevated levels of neurofilament light chain (NfL) at the start of the study experienced a rapid and sustained decrease in these levels after starting nusinersen, confirming the potential usefulness of NfL as an objective biomarker of disease activity and treatment response in SMA.

Nusinersen was generally well tolerated and no new safety concerns were raised during the eight-year follow-up. All participants experienced at least one adverse event, most of which were of mild to moderate severity; no adverse event resulted in treatment discontinuation or withdrawal from the study.

Source: press mat.