Vamorolone Efficacious in Treatment of DMD, Superior to Prednisone in Safety


Santhera and ReveraGen announced findings of the phase 2b VISION DMD study of the investigational therapy.

Dario Eklund, chief executive officer, Santhera

Dario Eklund

Vamorolone demonstrated safety and efficacy in the phase 2b VISION-DMD study (NCT03439670) in the treatment of individuals with Duchenne muscular dystrophy (DMD).

Both the low (2 mg/kg/day) and high dosages (6 mg/kg/day) showed strong efficacy in the study’s primary and secondary end points. The primary end point was superiority in change of time to stand from supine positioning to standing (TTSTAND) velocity with the high dose of vamorolone compared to placebo. The treated group had a difference of 0.06 (95% CI, 0.02-0.10) rises per second from baseline (P = .002). This is a clinically relevant improvement in TTSTAND 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.

“Today’s news is a tremendous milestone for patients and Santhera as we further advance vamorolone as a foundational treatment option in DMD. The treatment effect translates into the potential to delay disease progression by about two years and indicates disease modifying potential of vamorolone,” Dario Eklund, chief executive officer, Santhera, said in the company’s announcement. “We now look forward to working with regulatory authorities to bring vamorolone to DMD patients, first in the US and subsequently in Europe.

The 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.

READ MORE: Pamrevlumab, Vamorolone, and Others Headline Robust Pipeline in Duchenne Muscular Dystrophy

“We are thrilled about the positive results of the VISION-DMD study as it represents a culmination over a decade of scientific research,” Eric Hoffman, PhD, president and CEO, ReveraGen BioPharma and professor, Pharmaceutical Sciences, Binghamton University–State University of New York, added to the statement. “We are grateful to have been able to gather such important data and would like to thank all VISION-DMD participants, their families and caregivers, as well as investigators and study personnel, for their commitment to this ongoing program.”

The investigational agent from Santhera and ReveraGen is a first-in-class dissociative steroid that aims to retain the anti-inflammatory activity of corticosteroids while decreasing the deleterious adverse events (AEs). If successful, vamorolone may be a promising alternative to existing corticosteroids, the current standard of care in children and adolescent patients with DMD. The significant systemic AEs associated with high-dose corticosteroids diminish patient quality of life, so addressing these AEs is of high priority. Santhera noted that it plans to file a new drug application with the FDA in the first quarter of 2022, requesting priority review.

“The strength of evidence for both efficacy and safety of vamorolone over such a wide dose range from 2 to 6 mg/kg/day allows clinicians to individually tailor treatment of Duchenne patients by starting at the higher 6 mg/kg/day dose of vamorolone with equivalent efficacy to daily prednisone and titrate the dose according to how well the treatment is tolerated whilst maintaining optimal efficacy. I am enthusiastic that this approach may allow patients to avoid side effects that currently lead to discontinuing steroid treatment, meaning they are able stay on for longer,” Craig McDonald, MD, professor and chair, Department of Physical Medicine & Rehabilitation and Director of Neuromuscular Disease Clinics, UC Davis Health, said in the statement.

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-dosages showed favorable safety and tolerability profiles. No patients treated with vamorolone discontinued the study due to treatment-emergent AEs (TEAEs). The vamorolone-treated group had 96 TEAEs in the low-dose group and 91 TEAEs in the high-dose group compared to 120 TEAEs in the prednisone-treated group. Vamorolone high dose was found to be significantly superior to prednisone (P = .02) in a prespecified analysis of clinically relevant AEs.

Vamorolone did not show stunting of growth as reported with conventional corticosteroids in previously published results of 2.5-year (113 patient years) open-label studies. These results were validated in the double-blind study in which high dose vamorolone showed a significant difference in growth velocity compared to 0.75 mg/kg/day prednisone (P = .02).

“Stunting of growth is a major concern of families and patients treated with corticosteroids, and we are delighted to see this superiority of vamorolone proven in this double-blind study,” Paula Clemens, MD, study co-chair and vice chair, VA Affairs; and professor, Neurology, University of Pittsburgh School of Medicine, added to the statement.

Santhera and ReveraGen announce positive and statistically highly significant topline results with vamorolone in pivotal VISION-DMD study. News release. Santhera. June 1, 2021.
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