Clinical Trials

Date: 2016-11-07

Type of information: Results

phase: 3

Announcement: results

Company: Isis Pharmaceuticals (USA - CA), now Ionis Pharmaceuticals (USA - CA)

Product: Spinraza™ (nusinersen - ISIS-SMNRx - antisense oligonucleotide targeted to the SMN2 gene)

Action mechanism:

• antisense oligonucleotide. ISIS-SMNRx is designed to alter the splicing of a closely related gene (SMN2) to increase production of fully functional SMN protein. The FDA granted orphan drug status and fast track designation to ISIS-SMNRx for the treatment of patients with SMA. Isis is currently in collaboration with Biogen Idec to develop and potentially commercialize the investigational compound, ISIS-SMNRx, to treat all types of SMA. Under the terms of the January 2012 agreement, Isis is responsible for global development and Biogen Idec has the option to license the compound until completion of the first successful Phase 2/3 study or the completion of two Phase 2/3 studies.

Disease: spinal muscular atrophy 

Therapeutic area: Neuromuscular diseases - Rare diseases - Genetic diseases

Country: Australia, Canada, France, Germany, Hong Kong, Italy, Japan, Republic of Korea, Spain, Sweden, Taiwan, UK, USA

Trial details:

• CHERISH, a Phase 3 study of ISIS-SMNRx, is a randomized, double-blind, sham-procedure controlled fifteen month study in approximately 120 children who are non-ambulatory with SMA between the ages of 2-12. The study will evaluate the efficacy and safety of a 12 mg dose of ISIS-SMNRx with a primary endpoint of a change in the Hammersmith Functional Motor Scale-Expanded (HFMSE), a validated method to measure changes in muscle function in patients with SMA. Additional efficacy endpoints are also included in the study. (NCT02193074)

Latest news:

• • On November  7, 2016, Biogen and Ionis Pharmaceuticals announced that Spinraza™ (nusinersen), an investigational treatment for spinal muscular atrophy (SMA), met the primary endpoint at the interim analysis of CHERISH, the Phase 3 study evaluating Spinraza™ in later-onset (consistent with Type 2) SMA. The analysis found that children receiving Spinraza™ experienced a highly statistically significant improvement in motor function compared to those who did not receive treatment. Spinraza™ demonstrated a favorable safety profile in the study. Biogen is 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
• Results from the primary endpoint of the pre-specified interim analysis demonstrated a difference of 5.9 points (p= 0.0000002) at 15 months between the treatment (n=84) and sham-controlled (n=42) study arms, as measured by the Hammersmith Functional Motor Scale Expanded (HFMSE). From baseline to 15 months of treatment, patients who received Spinraza™ achieved a mean improvement of 4.0 points in the HFMSE, while patients who were not on treatment declined by a mean of 1.9 points. The HFMSE is a reliable and validated tool specifically 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. Data from the other endpoints analyzed were consistently in favor of children who received treatment. Spinraza™ demonstrated a favorable safety profile. The majority of the adverse events were considered to be either related to SMA disease, common events in the general population, or events related to the lumbar puncture procedure. No patients discontinued the study.
• With the positive interim analysis, the CHERISH study will be stopped and participants will be able to transition into the SHINE open-label extension study to receive Spinraza™. Full study results will be presented at future medical congresses.
• The FDA recently accepted the company's New Drug Application (NDA) for Spinraza™ as a treatment for SMA and communicated they plan to act early on the NDA under an expedited review. Additionally, the European Medicines Agency (EMA) recently validated Biogen's Marketing Authorization Application (MAA) in the EU. The EMA's Committee for Medicinal Products for Human Use (CHMP) granted Accelerated Assessment status and the FDA granted Priority Review to Spinraza™. Biogen is initiating regulatory filings in other countries in the coming months. Biogen initiated a global expanded access program (EAP) in infantile-onset SMA earlier this year. The company will continue to explore where and when the EAP may be broadened to include patients with later-onset SMA (consistent with Type 2).
• • On January 12, 2016, Ionis Pharmaceuticals announced that it has earned a milestone payment of $2.15 million from Biogen for completing the target enrollment of the Phase 3 CHERISH study. The study is designed to support marketing approval of nusinersen in children with spinal muscular atrophy (SMA). Ionis Pharmaceuticals also plans to complete enrollment in ENDEAR, a Phase 3 study evaluating nusinersen in infants with SMA, in the first half of 2016. Phase 3 date from both of these programs are expected in 2017.
• • On November 25, 2014, Isis Pharmaceuticals announced the initiation of a pivotal Phase 3 study evaluating ISIS-SMNRx in approximately 120 non-ambulatory children with spinal muscular atrophy (SMA). The Phase 3 study, CHERISH, is the second Phase 3 study Isis has initiated in a global late-stage clinical development program for ISIS-SMNRx. Isis earned a $27 million milestone payment from its development partner, Biogen Idec, for the dosing of the first patient in this study. CHERISH is the second pivotal Phase 3 study of ISIS-SMNRx the company has initiated this year. Isis is also evaluating ISIS-SMNRx in the Phase 3 study, ENDEAR, in infants with SMA. Isis is conducting both Phase 3 studies with agreement from the FDA for special protocol assessments, or SPAs.
• In addition to the current Phase 3 clinical studies ENDEAR and CHERISH,Biogen Idec plans to conduct two additional ISIS-SMNRx studies, which could begin in the first half of 2015:
• • NURTURE will be a Phase 2 clinical study evaluating ISIS-SMNRx in up to 25 pre-symptomatic newborns that are genetically predisposed to the disease.
• • EMBRACE will be a Phase 2 clinical study evaluating safety and exploratory efficacy of ISIS-SMNRx in approximately 20 patients with infantile or childhood-onset SMA. This study will bridge the gap in a small subset of patients that do not meet the age and inclusion criteria of the current Phase 3 studies ENDEAR and CHERISH.

Is general: Yes