Santhera's Duchenne effort gets a boost on positive PhIIa for alternative steroid vamorolone — though there's a lot left to prove
Months after Santhera got its hands on a second Duchenne muscular dystrophy drug, the Swiss company is getting an early look at how it improves muscle function. But serious questions remain as it takes on a field stuffed with entrenched rivals and controversy.
ReveraGen was in charge of the Phase IIa extension, which compared different doses of vamorolone with natural history controls. With 12 boys (aged 4 to 7) in each of four treatment groups, investigators tested 0.25, 0.75, 2.0 and 6.0 mg/kg/day in the study and published the results in Neurology.
Without spelling out numbers, the company noted that patients registered statistically significant and proportional improvements from baseline on multiple fronts, including the primary endpoint of time to stand from supine. Secondary endpoints regarding motor function outcomes span time to run/walk 10 meters, time to climb stairs, 6-minute walk test and North Star Ambulatory Test — with the highest dose outperforming the lowest in a notable manner.
Perhaps more importantly to their point, ReveraGen reported that vamorolone appears to trigger less adrenal suppression, insulin resistance and bone morbidities normally observed with other corticosteroids.
“Based on these data, vamorolone has potential to replace standard corticosteroids currently used in patients with DMD,” ReveraGen CEO said in a statement.
Corticosteroids such as prednisone and deflazacort represent the fundamental DMD treatments, providing a point of reference for new and experimental therapies. They are also dirt cheap, until Marathon acquired rights to deflazacort, rushed it through an FDA approval as Emflaza and jacked up the price from rouhgly $1,000 to $89,000 in a notorious case of price gouging. The availability of prednisone at pennies per pill, though, keeps the bar high on any replacement.
When Santhera acquired Idorsia’s option for vamorolone late last year (in exchange for $20 million upfront and 1 million shares), CEO Thomas Meier highlighted how it fits into their portfolio strategy to cover a broad Duchenne patient spectrum, “irrespective of genetic background, disease stage or age.” That’s in contrast with the targeted approaches others such as Sarepta and startup Exonics have taken, with their respective exon-skipping and gene editing efforts.
It has not worked out smoothly, though. Santhera’s other Duchenne candidate, idebenone, has previously been denied accelerated approval by the FDA and slapped down by the EMA. (The drug is marketed as Raxone in Europe to treat Leber’s hereditary optic neuropathy.)
But Santhera has since managed to notch orphan drug designations on both sides of the Atlantic and kickstarted a Phase III trial evaluating the efficacy of idebenone in delaying the loss of respiratory function in Duchenne patients already receiving corticosteroids.
Meanwhile, ReveraGen is in the midst of a Phase IIb study with 120 corticosteroid-naive boys, comparing the two highest doses of vamorolone (2.0 and 6.0 mg/kg/day) with prednisone and placebo. It’s slated to conclude next year.