According to a recent announcement, the FDA has accepted Santhera Pharmaceuticals and ReveraGen BioPharma’s New Drug Application (NDA) for the investigational drug vamolorone, a first-in-class dissociative steroid for the treatment of patients with Duchenne muscular dystrophy (DMD).1
The FDA has set a target action date for the PDUFA of October 26, 2023 and does not plan to hold an advisory board to discuss the application. If approved, the treatment is expected to launch in the fourth quarter later this year. This application is based on Phase 2b data from the VISION-DMD trial (NCT03439670), in which the drug met its primary endpoint of superiority in change in rise time test (TTSTAND) rate compared to placebo. rice field.
“We are pleased that the FDA has accepted Santhera’s application for the Bamorolone NDA. This product clearly addresses an unmet medical need and for Santhera, this is critical to our future success. We believe this represents an important milestone achieved,” Santhera, Chief Executive Officer of Dario Eklund, said in a statement.1 “We look forward to working closely with US regulators to advance vamolorone towards approval.”
VISION-DMD has demonstrated the efficacy, safety, and pharmacokinetics of oral vamolorone at 2.0 mg/kg/day and 6.0 mg/kg/day compared to prednisone at 0.75 mg/kg/day and placebo. It is a two-part exam that evaluates 24-week treatment period. This study included outpatient boys aged 4 to 7 with his DMD at 33 trial sites.
In the original analysis, published in June 2021, both treatment arms showed strong efficacy across the study’s primary and secondary endpoints. The superiority of change in TTSTAND velocity, the primary endpoint, was represented by an increase of 0.06 (95% CI, 0.02-0.10) per second from baseline in the treatment group (P. = .002). Specifically, researchers observed an improvement from 6.0 seconds to 4.6 seconds in the treatment group, and a corresponding deterioration from 5.4 seconds to 5.5 seconds in the placebo group.2
A secondary endpoint was also achieved, including TTSTAND rate in the low-dose group (P. = .02), high dose (P. = .003) and the low-dose group (P. = .009), and the duration of the 10 m running/walking test in the high-dose group (P. = .002). No statistically significant differences were observed between high-dose vamolorone and prednisone for secondary endpoints. Bamorolone had a better safety and tolerability profile than prednisone. The 24-week study was completed by his 114 (94%) of 121 patients. Both high and low doses showed favorable safety and tolerability profiles. Patients treated with vamolorone did not discontinue the study due to treatment-emergent adverse events (TEAEs).
“Data generated across the clinical trial program demonstrate that vamolorone may address relevant aspects of patient care and improve treatment outcomes,” said Dr. Eric Hoffman, president and chief executive officer. This is an exciting time for the Duchenne community as we are , ReveraGen said in a statement.1 “If approved, vamolorone could emerge as an additional treatment option in the current standard of care for DMD, addressing an unmet medical need and potentially providing early treatment for the majority of Duchenne patients.”
Results from Part 2 of the open-label VISION-DMD were presented at the 2022 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference. The open-label study included 121 boys with DMD who received placebo for 24 weeks (period 1) and an additional 24-week treatment period in two groups of vamolorone (2.0 or 6.0 mg/kg/day) switched to After her 24 weeks of treatment with the drug, the delayed starter showed improvement in multiple efficacy outcomes including her TTSTANDV (48 weeks vs. 24 weeks; P. <.05). Between the two groups, early starters on vamolorone 6.0 mg/kg/day had mean results compared with late starters for all five outcomes at all time points except the 10-meter walk test. value increased.3
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At the end of the 48-week period, only the time-to-climb test mean was statistically significant between early and late starters (P. <.05). Although no data were provided, the investigators found that other comparisons (vamorolone 2.0 mg/kg/day overall vs placebo to vamolorone 2.0 mg/kg/day or pooled dose groups) had similar results for the most part. pointed out that the
In September 2022, VISION-DMD researchers continued to publish additional data that extended the findings presented at MDA 2022. Exploratory endpoints, such as NorthStar Ambulatory Assessment (NSAA) total score and time to climb 4 stairs (TTCLIMB) speed, both showed improvements in favor of both high- and low-dose vamolorone groups compared to placebo. Patient-reported outcomes such as the Pediatric Outcome Data Collection Instrument (PODCI), Treatment Satisfaction Questionnaire (TSQM), and muscle strength measures are not statistically significantly different between the two groups. was. Specifically, a prespecified analysis of the Psychosocial Adaptation and Role Skills Scale III (PARS III) restricted to 4 of its 5 subscales showed that treatment with low-dose vamolorone, compared with prednisone, It was suggested to show better adaptation in anxiety and depression. However, this finding has not been reconciled after multiple tests.Four
The number of patients reporting at least one treatment-emergent adverse event (TEAE) was similar between groups, although the total number of TEAEs was lowest in the placebo group (n = 77) and the prednisone group (n = 121). ) was the highest. and intermediate of the two vamolorone groups (low dose: n = 97; high dose: n = 91). The only withdrawal from the study was from her one patient in the prednisone group, which the investigator considered possibly drug-related and remitted after drug discontinuation It was due to AE of personality change.