Months after axing a Duchenne program and laying off dozens, Santhera claims a win there with a different program
Last fall, Santhera Pharmaceuticals unceremoniously dumped a Duchenne program after it flunked a Phase III trial, forcing a wave of layoffs that trimmed the biotech’s staff from 120 to 40. Now, the Swiss company believes it’s found a path to a comeback with a different candidate in Duchenne.
Santhera revealed topline results from a Phase IIb study for its vamorolone program, saying two different doses each hit the primary endpoint compared with placebo. Tuesday’s data give the biotech confidence to potentially seek approval for both dosage levels with the aim of submitting an NDA in the first quarter of next year.
“This was the last thing that needed to fall into place for us to be, what I’m colloquially calling, Santhera 2.0,” CEO Dario Eklund told Endpoints News. “It’s really a new start for the company.”
The news sent Santhera shares skyrocketing in the Swiss stock exchange more than 60%.
Back in October, Santhera was forced to halt a Phase III study for its now-defunct idebenone program after it failed an interim analysis. The company had been ramping up for a potential commercial launch throughout Europe and had to withdraw its marketing authorization application from the EMA.
Most of the staffers laid off in the subsequent restructuring were stationed overseas in more than half a dozen European markets, Eklund said. The launch had been slated for the first quarter of this year, but the resulting failure forced Santhera to strip “down to the bones.”
Idebenone was designed to improve lung function in patients by energizing weakened muscle cells, and had long faced roadblocks in its development. The FDA rejected its original application for the program back in 2016 and asked for a confirmatory trial — the trial that Santhera terminated last fall.
But the vamorolone candidate functions similar to a steroid, which is the standard of care for many Duchenne patients. The Phase IIb study examined dosage levels of 2 mg/kg per day and 6 mg/kg per day, looking at how 121 patients’ time to stand from a supine position was shortened after 24 weeks of treatment.
In the high dose, patients reduced their time to stand from 6 seconds to 4.6 seconds, while the placebo group went from 5.4 to 5.5 seconds. That equated to a sparkling p-value of p=0.002. Santhera didn’t reveal the time difference for the lower dose, but reported a p-value here of p=0.02. There were “subtle differences” in the dose responses, vamorolone program lead Shabir Hasham told Endpoints.
Ideally, Santhera wants both doses to be approved so that patients have the option of down-titrating from the higher level if they experience side effects. There were no treatment-related side effects that registered at grade 3 or higher, but Hasham said about one-third of trial participants in the higher dose group moved down to the lower dose.
“Patients can start on a higher-dose therapy, and those who are comfortable can stay while others come down and don’t lose the efficacy,” Hasham said. “That’s really the unique thing.”
Conversations with regulators will dictate how Santhera ultimately moves forward, Eklund said. He hopes that because the candidate is an oral solution rather than a pill, Santhera’s pitch will prove persuasive — particularly given how typical corticosteroid treatments used for Duchenne can be down-titrated in a similar manner.
Last September, Santhera picked up global rights to vamorolone from ReveraGen after signing on to the option a few years ago. The company is looking to augment the Phase IIb data with results from a previously-reported Phase IIa study, which Hasham said now shows safety and tolerability of the program over 30 months.