While Novartis banishes Zolgensma scandal scars — Biogen goes on a Spinraza 'offensive'
While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza.
The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA.
Spinraza’s marketing application was given the nod largely on the basis of the pivotal 121-patient ENDEAR study, which showed 40% of patients treated with Spinraza saw an improvement in motor milestones, compared to none in the control arm. Long term data from 24 patients across different Spinraza trials found that children with later-onset SMA (Type 2 or Type 3) saw motor function stabilize or improve for up to nearly six years, in contrast to the expected decline if they did not receive treatment.
On Wednesday, Biogen said it was going to test a higher dose of Spinraza in a 126-patient trial to evaluate whether it was more potent (and safe) in SMA patients. The three-part trial includes an open-label safety evaluation, followed by a double-blind, randomized treatment period, which will lead to an open-label treatment period.
After the safety evaluation, the trial will compare two loading doses of 50 milligrams (mg), 15 days apart, followed by a maintenance dose of 28 mg every four months with the current FDA-approved administration of Spinraza, which is four loading doses with 12 mg maintenance doses every four months.
Biogen’s original dose 12 mg selection was based on preclinical data, Evercore ISI analyst Umer Raffat wrote in a note entitled “Spinraza on the offensive” last week.
The reason Biogen did not test a higher than 12 mg dose is due to preclinical toxicity concerns seen in monkeys, he added. “These monkey tox findings happened at 3 mg and 4 mg doses … human equivalent of this is 450-520 mg. For reference, the higher doses in new trial have annual Spinraza of 140-156 mg (i.e., well below).”
In terms of efficacy, a higher dose could potentially be beneficial, Raffat argued. “Higher dose could be better in infants … Ph 2 infantile onset shows much better motor milestones at 12 mg vs 6 mg. Even if 12 mg is optimal in infants, there’s still a possibility that the dose in teenagers/adults should be higher (was never tested).”
Meanwhile, Novartis $NVS and its AveXis unit are putting out fires surrounding Zolgensma, which was approved earlier this year. Priced at $2.1 million — it is the world’s most expensive therapy. Last month, it emerged AveXis had informed the FDA in late June about the manipulation of data used in its quest to procure FDA approval for Zolgensma.
Before that, safety was a potential concern, after a British infant succumbed to a severe respiratory infection followed by neurological complications in a European Zolgensma study. However, company executives on Thursday clarified that an investigation had concluded that the death was unrelated to the drug.
Executives representing the Swiss drugmaker also underscored positive long-term safety and efficacy data on the therapy.