FDA Approves Vamorolone as a Treatment for Duchenne Muscular Dystrophy

According to an announcement, the FDA has approved Santhera Pharmaceuticals' investigational agent vamorolone (now marketed as Agamree) oral suspension 40 mg/mL for the treatment of patients with Duchenne muscular dystrophy (DMD) aged 2 years and older. The therapy is a first-in-class dissociative steroid, that aims to retain the anti-inflammatory activity of corticosteroids while decreasing the deleterious adverse events (AEs).¹

Data from phase 2b data from the VISION-DMD study (NCT03439670) was the basis for the approval, in which the agent met its primary end point of superiority of change in time to stand test (TTSTAND) velocity relative to placebo. The primary end point, superiority in change of TTSTAND velocity, was represented by a difference of 0.06 (95% CI, 0.02-0.10) rises per second from baseline in the treated group (P = .002).

"This approval introduces a novel and alternative treatment choice for individuals dealing with DMD. Its distinctive structure and mechanism of action leads to tolerable side effects with matching efficacy to traditional corticosteroid treatment options and offers an excellent alternate treatment option," Stanley Iyadurai, MD, PhD, senior vice president of medical affairs and drug discovery at Catalyst Pharmaceuticals, told NeurologyLive^®. "This treatment represents a valuable addition to the range of tools available for managing patients with DMD. It can serve as a fundamental treatment option that can be added on to existing therapies, including exon-skipping therapies and dystrophin restoration therapies."

In July 2023, Catalyst Pharmaceuticals acquired the exclusive North American license and commercial rights for the agent from Santhera for DMD, as well as other potential indications. As part of that transaction, Santhera will transfer the approved new drug application (NDA) to Catalyst.

"We strongly believe that this novel steroid has the transformational potential to make a significant difference for patients living with Duchenne muscular dystrophy and potentially other chronic inflammatory diseases. The approval of Agamree underscores the potential of reshaping the DMD treatment paradigm for this life-threatening rare disease. The addition of Agamree expands our rare neuromuscular disease portfolio, and we look forward to executing on our proven commercial capabilities to bolster our long-term growth potential," Patrick J. McEnany, chairman and CEO of Catalyst Pharmaceuticals, said in a statement.¹ "Our unwavering commitment extends beyond this important milestone as we are resolute in our mission to ensure that DMD patients in the US have access to this treatment option as we believe that Agamree may offer the potential of increasing the duration of ambulation and mobility in these patients, thereby significantly improving their overall quality of life."

"We expect to launch the product in the first quarter of 2024. At that time, we will introduce a comprehensive financial assistance program aimed at helping ensure accessibility and minimizing patient copays and deductibles, thereby enhancing affordability for all DMD patients. We look forward to successfully commercializing this product with a continued commitment to serving our patient communities," McEnany continued.

VISION-DMD was a 2-part study that assessed the efficacy, safety, and pharmacokinetics of vamorolone administered orally at daily doses of 2.0 mg/kg/day and 6.0 mg/kg/day vs prednisone 0.75 mg/kg/day and placebo over a 24-week treatment period. The study featured ambulatory boys aged 4 to 7 years old with DMD across 33 trial sites.

In the original analysis published in June 2021, both dosed groups showed strong efficacy in the study’s primary and secondary end points. Specifically, investigators observed improvements from 6.0 to 4.6 seconds in the treated group and a corresponding deterioration in the placebo group from 5.4 to 5.5 seconds.²

Secondary end points were also met, including TTSTAND velocity in the low-dose group (P = .02), 6-minute walk test in the high-dose (P = .003) and low-dose group (P = .009), and time to run/walk 10 m test in the high-dose group (P = .002). No statistically significant differences were observed between vamorolone high dose and prednisone on the secondary end points. Vamorolone showed a favorable safety and tolerability profile over prednisone. The 24-week study was completed by 114 of 121 patients (94%). Both the high- and low-doses showed favorable safety and tolerability profiles. No patients treated with vamorolone discontinued the study due to treatment-emergent AEs (TEAEs).

Clinical Takeaways

The FDA approved vamorolone (Agamree) for DMD in patients aged 2 and older, offering a novel dissociative steroid with the potential to reduce adverse events while retaining its anti-inflammatory effects.
Vamorolone demonstrated efficacy in improving various DMD-related end points, including time to stand test velocity, in a clinical study with favorable safety and tolerability profiles compared with prednisone.
Catalyst Pharmaceuticals plans to launch Agamree in the first quarter of 2024 with a financial assistance program to enhance accessibility, potentially improving the quality of life for DMD patients.

Results from part 2 of VISION-DMD, the open-label portion, were presented at the 2022 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference. The open-label study included 121 boys with DMD to placebo for 24 weeks (period 1) who crossed over to 2 vamorolone groups (2.0 or 6.0 mg/kg/day) for another 24-week treatment period. After 24 weeks of treatment with the agent, delayed starters demonstrated improvement on multiple efficacy outcomes including TTSTANDV (week 48 vs week 24; P <.05). Between the 2 groups, early-starters on vamorolone 6.0 mg/kg/day had increased outcome means relative to the delayed-starters for all 5 outcomes at all time points except for 10 Meter Walk Test.³

At the end of the 48-week period, only the mean for Time to Climb Test was statistically significant between early- and delayed-starters (P <.05). Although the data were not provided, investigators noted that other comparisons (vamorolone 2.0 mg/kg/day throughout vs placebo-to-vamorolone 2.0 mg/kg/day or pooled dose groups) yielded similar findings for the most part.

"Corticosteroids have been a first-line treatment for DMD for many years but their utility has always been limited by the side effect profile, which includes weight gain, short stature, and decreased bone density among others. The approval of Agamree provides those living with Duchenne, and their families, a powerful tool to treat the disease, while limiting some negative [adverse] effects associated with corticosteroids,” Sharon Hesterlee, PhD, Chief Research Officer of the MDA, said in a statement.⁴ “MDA is extremely proud to have been involved with vamorolone since its inception. It was one of the earliest investments to be made by our venture philanthropy arm and we are gratified to see that paying off in the form of a viable new therapy for Duchenne patients and the community.”

Eric Hoffman, PhD, the associate dean of Research and Research Development and a professor of Pharmaceutical Services at Binghamton University, who cofounded Reveragen—the company that originally developed vamolorone—added that “the main concern was getting an effective treatment to children as quickly as possible. This was truly a community effort and getting a multitude [of] perspectives and feedback from MDA and others helped make this a reality for so many families.”⁴

In September 2022, investigators from VISION-DMD continued to publish additional data that expanded on the findings presented at MDA 2022. Exploratory end points, such as NorthStar Ambulatory Assessment (NSAA) total score and time to climb 4 stairs (TTCLIMB) velocity, both showed improvement that favored both the high- and low-dose vamorolone groups compared with placebo. Between the 2 groups, patient reported outcomes such as Pediatric Outcomes Data Collection Instrument (PODCI) and Treatment Satisfaction Questionnaire (TSQM), as well as measures of muscle strength, were not statistically significantly different. Notably, in a prespecified analysis of Psychosocial Adjustment and Role Skills Scale III (PARS III) limited to 4 of 5 subscales, findings suggested that treatment with low dose vamorolone showed better adjustment for anxiety and depression compared with prednisone. This finding however was not adjusted after multiple testing.⁵

While the number of patients reporting at least 1 treatment-emergent adverse event (TEAE) was similar between groups, the total count of TEAEs was lowest in the placebo group (n = 77), highest in the prednisone group (n = 121), and intermediate in the 2 vamorolone groups (low dose: n = 97; high dose: n = 91). The only withdrawal from the study was from 1 patient in the prednisone group, owing to an AE of personality change that was viewed by the investigator as possibly related to the drug and abated after cessation of the drug.

Edward Smith, MD, adjunct professor of pediatrics at Duke University Medical Center and medical director and principal investigator at Rare Disease Research-NC, LLC, said in a statement, “Having a novel steroid available that provides the benefits of current steroid therapy but with fewer [adverse] effects is a big step forward in treatment options. You can really see the difference with Agamree. Boys are taller and improved bone health may help them avoid painful fractures that can lead to even earlier loss of ambulation."⁴