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Boys with Duchenne muscular dystrophy (DMD) got the same benefit from 30 months of treatment with a novel type of corticosteroid as would be expected with conventional versions, a researcher reported, but without most of the adverse effects typically seen with such agents.

In 23 boys receiving the investigational drug vamorolone, mean trajectories of muscle function as measured by time to stand and time to run or walk 10 meters were the same as in a historical cohort (n=75) of boys receiving conventional steroids including prednisone and deflazacort (Emflaza), according to Stefan Jackowski, PhD, of the Ottawa Pediatric Bone Health Research Group in Ontario.

Yet while the historical cohort showed the classical negative effects on stature and bone structure with long-term conventional steroid therapy, these did not occur in the patients treated with vamorolone, Jackowski told attendees at the American Society for Bone and Mineral Research's annual meeting, held online and in San Diego.

The only adverse effect still seen with vamorolone was weight gain, with predicted trajectories the same as those documented in the control cohort.

Corticosteroids remain the mainstay of DMD therapy, even after the approval of putatively disease-modifying drugs such as eteplirsen (Exondys 51), which haven't conclusively shown clinical benefits. As Jackowski explained, steroids keep DMD kids walking longer, decrease their risk of scoliosis, and allow most to live at least into their 20s. But "harsh side effects limit their use," he noted. Years of steroid therapy lead to growth inhibition and weakened bone structure, with patients increasingly susceptible to fractures.

Vamorolone is designed to be a "dissociative steroid" -- a term invented by its developers to describe their goal of separating the desired clinical effects from the undesired. The chemical structure of vamorolone is nearly identical to that of prednisolone (the active form of prednisone) but with one modification altering its contact site with steroid receptors. In doing so, the molecule retains the anti-inflammatory activity expected from steroids while dropping the "positive transcriptional activity" driving the adverse effects, Jackowski said.

The commercial developer, Maryland-based ReveraGen BioPharma, has sponsored two open-label, dose-finding trials with vamorolone in boys with DMD who had not previously received steroids. Of the total 48 enrolled in these studies, 23 received at least 2 mg/kg/day for 30 months, and this was the group on which Jackowski focused his presentation.

For comparison, he and colleagues obtained data on 75 boys from a , treated with steroids for at least 6 months (mean 24 months). These 75 were matched to the 23 treated with vamorolone by baseline age after they'd been in treatment for 6 months. All patients in both groups were able to walk at baseline.

Mean age in the two groups was similar at about 6. By the time they'd been on treatment 6 months, those receiving vamorolone were somewhat bigger for their age than the control cohort, by both height and weight, but were very similar in functional performance.

As expected, vamorolone was not a cure. Muscle function showed an overall downward trend over the full 30 months of treatment, at rates similar to patients in the conventionally treated cohort.

Where the groups did differ substantially was in predicted height trajectories. Those receiving vamorolone at 2 mg/kg/day or higher showed them catching up a bit with their healthy peers, whereas growth virtually stopped in those on long-term conventional steroids.

After 3 years, 10% of the vamorolone cohort had experienced vertebral fractures (identified on imaging in central analyses) compared with 20% of patients in a different historical cohort receiving daily prednisone. Structural analyses of bone age showed that it was only minimally delayed, "which in the setting of improved growth on vamorolone compared with traditional [steroids] is anticipated to benefit adult height," Jackowski said.

He also addressed vamorolone's safety. One of the dosage groups in the phase II studies was 6 mg/kg/day, and one-quarter of this group had the dosage reduced because of new-onset weight gain. Five boys in all suffered clinical fractures, two of which were in the spine. Two serious treatment-emergent events were recorded -- one case each of pneumonia and myoglobinuria -- but these were considered unrelated to vamorolone.

Perhaps the most important question surrounding vamorolone didn't come up in Jackowski's presentation. If this drug genuinely does "dissociate" the benefits from the adverse effects, could it be used in many rheumatologic and other conditions for which steroids are often prescribed, or would be if not for the side effects?

ReveraGen says yes, for sure. The company currently has a phase I/II trial , and its that it sees potential in asthma, rheumatoid arthritis, multiple sclerosis, and several less common disorders.

As for the DMD indication, the company said it successfully completed a pivotal study (full results not published yet; were announced in June), and U.S. marketing approval will be sought early next year.

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