Important Milestone Reached with First New Drug Program for SMA Advancing Towards Approval with the FDA

Biogen and Ionis have been testing nusinersen in clinical trials and today announced that they will close ENDEAR, the Phase 3 trial testing nusinersen in infants with SMA type 1. The trial met the primary endpoint pre-specified for the interim analysis of ENDEAR, the Phase 3 trial evaluating nusinersen in infantile-onset (consistent with Type 1) SMA. The analysis found that infants receiving nusinersen experienced a statistically significant improvement in the achievement of motor milestones compared to those who did not receive treatment. Nusinersen demonstrated an acceptable safety profile in the trial. As a result of these findings, Biogen will also initiate regulatory filings globally in the coming months.

Starting in 2003, Cure SMA provided the seed funding needed to begin investigation into this therapeutic approach. The intellectual property generated with our funding was then licensed to Ionis Pharmaceuticals to create nusinersen, the drug that will soon be brought to the FDA for approval.

More Information on Today’s Important Announcement

“We are grateful to the families participating in the clinical trials, who continue to inspire us. We want to thank them, along with the investigators who have worked tirelessly on this program and the broader SMA community, for their partnership. Without their contributions, we would not be here today,” said Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “We share the community’s sense of urgency as we strive to bring the first treatment for SMA, the leading genetic cause of infant mortality, to families facing this devastating disease. We remain committed to understanding the potential of nusinersen in the broader SMA population and will continue to focus on the rapid completion of our ongoing studies.”

Based on the results of the pre-specified interim analysis, the ENDEAR study will be stopped and participants will be able to transition into the SHINE open-label study in which all patients receive nusinersen. Data from the other endpoints of ENDEAR will be analyzed when the full data set is available. Results will be presented at future medical congresses. Additionally, participants enrolled in the sham-controlled arm of EMBRACE, a Phase 2 study which also included infantile-onset patients, will have the opportunity to receive nusinersen.

Ongoing Studies

The other studies in the nusinersen program, including CHERISH (later-onset consistent with Type 2) and NURTURE (pre-symptomatic infants), will continue as planned in order to collect the data to demonstrate the safety and efficacy of nusinersen in these populations.

“We are hopeful that nusinersen, if approved, will make a meaningful difference in the lives of patients and families affected by SMA. We look forward to working with Biogen on completing the clinical program and preparing for what we hope is a positive regulatory review,” said B. Lynne Parshall, chief operating officer at Ionis Pharmaceuticals. “Nusinersen is the first antisense drug from our neurological disease franchise to advance to regulatory review, and it illustrates the potential of our antisense technology to address severe diseases that other therapeutic modalities are unable to address adequately.”

“Today is a hopeful day for the SMA community, which has worked tirelessly to support research and development for this terrible disease. Many of our families have participated in this and other clinical trials in order to advance our understanding of SMA. We are excited about reaching this important milestone, and the opportunity these results create to potentially bring the first treatment option for SMA to patients and families. We will continue to relentlessly support research into SMA until we have therapies for all and, ultimately, a cure,” commented Kenneth Hobby, President, Cure SMA.

Expanded Access Program

Biogen is working to open a global expanded access program (EAP) for eligible patients with infantile-onset SMA (consistent with Type 1) in the coming months. The EAP can be initiated at existing nusinersen clinical trial sites in countries where EAPs are permitted according to local laws and regulations, can be operationalized, and where there is a path that can support long-term availability of nusinersen. Once the EAP is operational and required local approvals are in place, individual participating sites may start enrollment after they have transitioned ENDEAR study participants to the open-label extension study.

More information on the EAP can be found on the website under the NCT identifier NCT02865109.

Next Steps

Biogen is now responsible for all nusinersen development, regulatory and commercialization activities and costs. Ionis will complete the Phase 3 studies and work with Biogen on regulatory filings. The two companies will also work together to transition the clinical programs that Ionis is conducting to Biogen.

In the United States, the Food and Drug Administration (FDA) is responsible for granting marketing approval for drugs. If a drug developer has evidence from clinical trials that a drug is safe and effective for its intended use, the company can file a new drug application (NDA). The FDA review team thoroughly examines all submitted data on the drug and makes a decision to approve or not to approve it.

When the FDA evaluates a drug for approval, they must weigh many different factors, including the quantity and quality of evidence of safety and effectiveness, potential benefits of a treatment versus the potential risks, and the impact the treatment will have on the patient community. While we wait for the NDA to be reviewed, we won’t sit back. We are actively working to continue our ongoing efforts to make sure that our community’s voice is heard when a drug comes forward for approval.

Once the NDA documents are submitted, the FDA has 60 days to review and either accept or reject the initial submission. Once the submission has been accepted, the typical review time is 10-12 months. Biogen is currently working with the FDA to explore opportunities to expedite this timeline.

We will have more information on this important development in the coming days and weeks.

Cure SMA would like to thank and acknowledge Cold Spring Harbor Laboratory (CSHL) and the University of Massachusetts Medical School for generating critical intellectual property for the program that was licensed to Ionis Pharmaceuticals. We specifically thank Dr. Adrian Krainer and his colleagues at CSHL for years of dedication to and hard work on the preclinical development of nusinersen for SMA, and Drs. Ravindra Singh and Elliot Androphy for their work funded by Cure SMA in originally identifying the ISSN1 gene sequence, which is the sequence targeted in nusinersen. In addition, Drs. Krainer and Androphy are long standing members of the Cure SMA Scientific Advisory Board.

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