Biogen ($BIIB) and drug partner Ionis ($IONS) posted more positive data from another late-stage trial for nusinersen, now known as Spinraza, for the rare but devastating fatal childhood disease spinal muscular atrophy (SMA).
In the keenly awaited Cherish Phase III test, kids with Type 2 SMA showed a “highly statistically significant” improvement in motor function compared to those who did not receive treatment, when using the med, which also showed a favorable safety profile.
Cherish, a 15-month study of 126 patients who can’t walk, showed that, as measured by an accepted medical scale via a points system, from baseline to 15 months of treatment patients who received Spinraza achieved a mean improvement of 4 points, while patients who were not on treatment declined by a mean of 1.9 points.
This Hammersmith Functional Motor Scale Expanded points scale is designed to assess motor function in children with SMA, and a change of three points or greater in the HFMSE has previously been identified as clinically meaningful, the biotechs say in a statement.
This test will now be stopped, and patients can move over to its Shine open-label extension study. Full study results will be presented at future medical congresses, the biotechs added.
SMA affects around 1 in 10,000 babies, and about 1 in every 50 Americans is a genetic carrier. The disease has four types, with Type 1 being the most severe: Around 90% of children born with this type never see their second birthday, and in their short lives will never sit, crawl or walk.
Types 1, 2 and 3 appear in childhood; Type 4, also known as adult-onset SMA, appears in adulthood.
Symptoms of SMA Type 2, also known as intermediate SMA or chronic infantile SMA, include muscle weakness and floppiness that usually appear between 7 and 18 months of age.
In SMA Type 3, sometimes called Kugelberg-Welander disease, symptoms of muscle weakness and floppiness appear after 18 months of age, but the actual age of onset is very variable and symptoms may not appear until late childhood or early adulthood. Biogen and Ionis’ program has been looking across the first three types.
The Big Biotech said it is already preparing for the potential launch of Spinraza in the U.S. “possibly as early as the end of 2016 or the first quarter of 2017.”
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 median duration of therapy and a $250,000 price, according to Evercore ISI analyst Mark Schoenebaum.
Evercore analysts said of these latest data: “We reached out to BIIB, who noted that regulators will be made aware of the CHERISH data (presumably asap) and that they are preparing for a U.S. launch as early as by YE 2016 or 1Q17 (note that suggests a potential US approval ahead of the PDUFA date).
“We believe today’s positive topline read out from Cherish in Type 2 materially increases the probability of obtaining a broad initial label, whereas investors had previously been skeptical.”
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 $150 million in milestones. Biogen is assuming clinical trial costs going forward and will lead global commercialization, with Ionis getting a tiered royalty of up to a mid-teens percentage of sales.
This builds on other positive data coming out of the pair’s lab this year, including the Phase III Endear study, where their med showed statistically and clinically significant improvement in the primary endpoint, which included greater movement in kicking, walking, crawling and sitting, than worsened.
As well as its Endear test, geared up for patients with infantile-onset SMA (who are most likely to develop Type 1), it also posted what it called “encouraging preliminary results from Nurture,” a Phase II open-label study in presymptomatic infants, as well as a recent analysis of the ongoing midstage open-label study in patients with later-onset SMA (consistent with Types 2 or 3).
Nusinersen works as an antisense oligonucleotide that is designed to alter the splicing of SMN2, a gene that is nearly identical to SMN1, in order to increase production of fully functional SMN protein.
But it’s not the only one in this space, with Roche-backed AveXis ($AVXS) releasing new data a month ago from its small Phase I study of the FDA breakthrough-designated gene therapy AVXS-101.
These data showed that, as of Sept. 15, two-thirds of patients in cohort 2 (which is what the company is looking to dose its patients on) “had achieved the ability to sit unassisted, including one patient whose achievement of this milestone was confirmed after September 15.”
AVXS-101 is designed to address the monogenetic root cause of SMA and prevent further muscle degeneration by addressing the defect in and/or loss of the primary SMN gene.
Roche ($RHHBY) and one of its other SMA partners, PTC Therapeutics ($PTCT), will also next year start a midstage study for its candidate against certain forms of SMA.
The Phase II Sunfish study will specifically look at both younger and adult Type 2/3 SMA patients using RG7916, a med that has the backing of Roche. Biogen and its partner are however ahead of AveXis and PTC, and likely to be first to market the first med for this disease.
Biogen, which is losing its CEO and having deep questions raised over its MS franchise, as well as the risk attached to its Alzheimer’s program, could do with some good news. So too could Ionis, which tanked in May after partner Glaxo ($GSK) decided to postpone its decision to start a large outcome study in patients with TTR cardiomyopathy (the CARDIO-TTR study) until after they could evaluate results from the NEURO-TTR study.
Biogen was up 5.5% this morning after the news, while Ionis was up nearly 21%.