Biogen Completes Rolling Submission of New Drug Application to FDA

By Cure SMA | Published On November 29, 2016

 Biogen Completes Rolling Submission of New Drug Application to FDA

Biogen and Ionis today announced that Biogen has completed the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the approval of nusinersen, an investigational treatment for spinal muscular atrophy (SMA). Biogen has also applied for Priority Review which, if granted, would shorten the review period of nusinersen following the Agency’s acceptance of the NDA.

“Since announcing the positive results of the ENDEAR interim analysis in infantile-onset SMA last month, we have heard from many families expressing their excitement about nusinersen. Their stories continue to inspire us and they are in the forefront of our minds as we work to support the FDA’s review of nusinersen,” noted Alfred Sandrock, M.D., Ph.D., executive vice president and chief medical officer at Biogen. “We appreciate the FDA’s collaboration with us during the application process, and we look forward to continuing this productive dialogue, with the goal of rapidly bringing the first treatment for SMA to as many patients as possible.”

In addition to the NDA filing with FDA, Biogen plans to submit a Marketing Authorization Application (MAA) for nusinersen to the European Medicines Agency (EMA) in the coming weeks. The EMA’s Committee for Medicinal Products for Human Use (CHMP) recently granted Accelerated Assessment to nusinersen, which can reduce the standard review time. Biogen will initiate regulatory filings in other countries in the coming months.

“Our ability to advance the nusinersen program as quickly as we have is largely due to the tremendous contributions of the entire SMA community, from the patients and families who participated in the clinical trials to the doctors, nurses and advocates who work tirelessly on their behalf,” said B. Lynne Parshall, chief operating officer at Ionis Pharmaceuticals. “We are deeply appreciative of their unwavering commitment to finding a treatment for SMA and today’s milestone is truly a collective achievement.”

The regulatory submissions are comprised of results from the pre-specified interim analysis of ENDEAR, the controlled Phase 3 study evaluating nusinersen in infantile-onset (most likely to develop Type 1) SMA, as well as all other clinical and preclinical data currently available, which includes open-label data in other patients types. The ENDEAR interim analysis demonstrated that infants receiving nusinersen experienced a statistically significant improvement in the achievement of motor milestones compared to those who did not receive treatment. Biogen anticipates hearing from regulatory authorities regarding the acceptance and validation of these submissions within the next couple of 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 Nusinersen Clinical Trial Program

The nusinersen clinical trial program is comprised of two controlled studies, ENDEAR and CHERISH. ENDEAR was designed as a thirteen-month study investigating nusinersen in 122 patients with infantile-onset SMA; the onset of signs and symptoms of SMA less than or equal to 6 months of age and age less than or equal to 7 months at screening. Based on the results of the pre-specified interim analysis, the ENDEAR study will be stopped; patients who elect to are currently being transitioned to the SHINE open-label study where they will all receive nusinersen. Results from the ENDEAR interim analysis will be presented at future medical congresses.

CHERISH is a fifteen-month study investigating nusinersen in 126 non-ambulatory patients with later-onset SMA, consistent with Type 2; onset of signs and symptoms greater than 6 months and age 2 to 12 years at screening. CHERISH was fully enrolled in May 2016 and remains ongoing.

Additionally, the SHINE open-label extension study, for patients who previously participated in ENDEAR and CHERISH, is open and is intended to evaluate the long-term safety and tolerability of nusinersen.

Two additional Phase 2 studies, EMBRACE and NURTURE, were designed to collect additional data on nusinersen. The EMBRACE study is designed to collect additional data on a small subset of patients with infantile or later-onset SMA who do not meet the age and other criteria of ENDEAR or CHERISH. Due to the evidence demonstrated in the infantile-onset SMA (most likely to develop Type 1) population, the sham arm of the EMBRACE study is being stopped and patients are being given the option to receive nusinersen through an open-label extension study. NURTURE is an open-label, ongoing study in pre-symptomatic infants who are less than or equal to 6 weeks of age at time of first dose to determine if treatment before symptoms begin would prevent or delay onset of SMA symptoms.

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.

Now that 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.

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

Topics: Clinical Trials, Advocacy

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