Spinraza (nusinersen) for spinal muscular atrophy (SMA) met the primary endpoint in an interim analysis from a Phase 3 clinical trial evaluating the treatment in children with later-onset (consistent with Type 2) SMA.
Biogen and Ionis Pharmaceuticals reported that children treated with Spinraza had a highly statistically significant improvement in motor function, and the treatment was associated with a favorable safety profile.
Biogen hopes to launch Spinraza in the United States soon — later this year or early in 2017. The drug still needs FDA approval.
“These results, along with our successful trial in infantile-onset SMA, reinforce the potential of Spinraza to benefit a broad range of SMA patients,” Michael Ehlers, MD, PhD, executive vice president and head of research and development at Biogen, said in a press release.
“We will make regulators around the globe aware of this data and will continue working closely with them to bring Spinraza to families affected by SMA as quickly as possible.”
Spinraza is an investigational antisense oligonucleotide (ASO) created to alter the expression of SMN2, a gene that is nearly identical to SMN1, in order to increase production of fully functional SMN protein, which is absent in SMA.
ASOs are short synthetic strings of nucleotides — basic structural units of nucleic acids such as DNA — designed to selectively bind to target ribonucleic acid (RNA) and regulate gene expression. With this technology, Spinraza can potentially increase the amount of functional SMN protein in children and infants with SMA.
The drug is currently being tested in two Phase 3 clinical trials: CHERISH (childhood-onset) and ENDEAR (infant-onset), and two Phase 2 studies called EMBRACE and NURTURE.
The interim results reported this week refer to CHERISH, a randomized, double-blind, 15-month clinical trial (NCT02193074) evaluating the effectiveness and safety of 12 mg doses of Spinraza in 126 non-ambulatory children with later-onset SMA (consistent with Type 2), ages 2 to 12.
A total of 84 children received treatment with Spinraza and 42 have not received treatment with the drug. The primary endpoint of the trial is the assessment of change in muscle function as measured with the Hammersmith Functional Motor Scale-Expanded (HFMSE).
Results from the interim analysis showed that from baseline to 15 months of treatment, Spinraza-treated children had a mean improvement in motor function of 4.0 points as measured by the HFMSE (3 points or more indicate improvement in motor function).
Children who did not receive Spinraza in the trial had a mean 1.9-point decline in HFMSE, the companies reported. No treatment-related adverse events were reported.
Based on these positive interim results, CHERISH will be stopped and patients will be moved into the SHINE study (NCT02594124), an open-label extension trial evaluating the clinical safety, tolerability, and effectiveness of Spinraza in children with SMA.
“These data further validate the potential of Spinraza as a treatment for patients with SMA,” said B. Lynne Parshall, chief operating officer of Ionis Pharmaceuticals. “We are grateful to all the families and clinicians who have participated in all of the Spinraza studies. Without their commitment and support, this program would not have been able to progress so quickly.”
Regulatory agencies in the U.S. and European Union have granted Spinraza special status intended to expedite the investigative review process, including FDA Orphan Drug status and Fast Track Designation, and Orphan Drug Designation in the E.U.
The FDA recently accepted a New Drug Application (NDA) for marketing approval for Spinraza, and the European Medicines Agency (EMA) recently validated a Marketing Authorization Application.
The EMA’s Committee for Medicinal Products for Human Use (CHMP) granted Accelerated Assessment status and the FDA granted Priority Review to Spiranza. Biogen plans to initiate more regulatory filings in other regulatory jurisdictions in coming months.