Biogen ($BIIB) has clocked a win on Phase III data for nusinersen to treat rare, severe genetic disease spinal muscular atrophy (SMA) with partner Ionis Pharmaceuticals ($IONS). The trial was unblinded early at an interim endpoint due to significant improvement in motor milestones in treated versus untreated infants. The drug is expected to become a blockbuster, exceeding $1 billion in annual sales--good news for both of the recently beleaguered companies.
It has paid Ionis a $75 million fee to exercise its option to develop and market nusinersen globally; it expects to start regulatory filings for nusinersen “in the coming months.” There is currently no approved treatment of SMA which results in severe and progressive muscular atrophy and weakness, with the most severe type resulting in paralysis and death.
Nusinersen met the primary endpoint of significant improvement in achievement of motor milestones as compared to untreated patients in the ENDEAR study, but further data details are as yet undisclosed. The study has been stopped and all patients in this trial as well as in the sham-controlled arm of another study, EMBRACE, will transition to nusinersen; data from the other ENDEAR endpoints will be analyzed at a later point when the full data set is available.
“Infants treated with nusinersen demonstrated a highly statistically significant improvement in the achievement of motor milestones has measured by the Hammersmith Infant Neurological Examination, compared to those who did not receive version,” said Ionis chairman and CEO Stanley Crooke on a conference call about the data.
“The responder analysis conducted looked at achievement of tangible milestones like kicking, head control, rolling, sitting, crawling, standing, and in some cases even walking. So, it provides a real demonstration of the value that nusinersen may be bringing to these patients and their families in their everyday lives. Nusinersen also demonstrated an acceptable safety profile in the trial,” he added.
The full data from this trial, known as ENDEAR, hadn’t been anticipated until the first half of next year. It’s a 13 month, 122-patient study in infantile-onset SMA.
There are about 15,000 SMA patients in the U.S. Wall Street is modeling a consensus expectation of peak annual sales of $1.7 billion by 2025 for nusinersen, which assumes about a 45% penetration with a one year mediation duration of therapy and a $250,000 price, according to Evercore ISI analyst Mark Schoenebaum.
Biogen partnered with Ionis in SMA in 2012--prior to the latter’s subsequent name change from Isis Pharmaceuticals. If nusinersen is approved globally, Ionis will gain $150 million in milestones. Biogen is assuming clinical trial costs going forward and will lead global commercialization, with Ionis getting a tiered royalty of up to a mid-teens percentage of sales.
Summed up Scangos on the next clinical steps for nusinersen, “Ionis and Biogen will continue to work to identify the quickest path forward to collect the necessary data from CHERISH, a Phase III study investigating nusinersen inpatients with childhood-onset SMA and with NURTURE a Phase II study in pre-symptomatic infants - so the regulators can evaluate the safety and efficacy of nusinersen in these populations.”
Nusinersen is an antisense oligonucleotide designed to alter the splicing of SMN2; it’s intended to increase production of fully functional SMN protein.
Both Biogen and Ionis have been troubled of late. The former is losing its head, George Scangos, who turned around the company years ago with its multiple sclerosis franchise, but it has since been stymied more recently by slowing sales of its Tecfidera.
For its part, Ionis tanked in May after partner GlaxoSmithKline ($GSK) opted not to continue after a clinical trial hold for IONIS-TTRRx in an ongoing Phase III study, NEURO-TTR, in patients with transthyretin (TTR) familial amyloid polyneuropathy. At that time, there was some concern that the safety issues, which included severe declines in platelets, that had also been an issue for Ionis’ volanesorsen could extend across the entire platform of the company.
Biogen chose the earliest potential time to opt-in on this deal, making this a strong testament of its faith in the program going forward. In early trading on the news, Biogen tipped up about 5% while Ionis shares leapt up by almost 30%
- here is the release