FDA Will Review Nusinersen for Treatment of SMA

Nusinersen The U.S. Food and Drug Administration (FDA) has accepted Biogen’s New Drug Application for nusinersen (brand name Spinraza) for the treatment of spinal muscular atrophy (SMA) and granted Priority Review.

Priority Review status is reserved for drugs that offer significant improvements over existing options or provide a treatment for a disorder for which no approved treatment currently exists, and shortens FDA review time from 10 months to a goal of six months.

The FDA will now begin to review the data package Biogen has submitted in support of its application for nusinersen, and an advisory committee meeting may be held prior to an FDA decision. At these meetings, representatives from Biogen will present the evidence to support approval to a panel of experts who may then be called on to vote in support of, or against, approval of the drug. Patient advocacy groups, individuals and families who participated in clinical trials for the drug, and other members of the public also have a chance at these meetings to speak to the committee and share patient and caregiver perspectives, plus other considerations about the drug.

A decision on nusinersen, which previously has received Fast Track status and Orphan Drug designation and from the FDA, is anticipated in spring 2017.

Nusinersen is designed to modify SMA

In SMA, very little full-length SMN protein is made. Instead, most of the SMN is in the form of a short, unstable protein. Full-length SMN is needed by muscle-controlling nerve cells, known as motor neurons, in the spinal cord. Without the protein, loss of motor neurons from the spinal cord occurs, with resulting weakness and atrophy of the voluntary muscles. In the severest forms of the disease, premature death may occur because of failure of the respiratory (breathing) muscles.

Infants with type 1 SMA can’t sit or hold their heads up, and progressively lose what movement ability they have. These babies typically don’t live past the age of 1 year, with death often due to respiratory failure unless the infant is placed on a ventilator. Other, milder forms of SMA (types 2, 3 and 4) involve difficulties with movement and are associated with a normal or somewhat reduced lifespan.

Nusinersen is a disease-modifying antisense drug, one of a class of experimental therapeutic molecules designed to target genetic instructions at the RNA stage (an intermediate step between DNA and the protein manufacturing stage inside cells). It is designed to increase production of the needed SMN protein.

Nusinersen clinical trials

Ionis Pharmaceuticals and Biogen have been testing nusinersen both in blinded and open-label studies, and in patients with types 1, 2 and 3 SMA.

Interim analysis from the phase 3 ENDEAR trial, conducted in 120 infants with type 1 SMA, found that the drug was safe and well-tolerated and that infants receiving nusinersen experienced a statistically significant improvement in the achievement of motor milestones compared to those who did not receive treatment. In rare instances, as with the ENDEAR trial, when evidence of efficacy is sufficiently strong, a blinded trial can be halted so all patients can benefit from treatment. Along with ENDEAR participants, patients in the control sections of a phase 2 study called EMBRACE also are eligible to transition to the SHINE open-label study which aims to evaluate the long-term safety and tolerability of nusinersen.

Other studies of nusinersen are ongoing. These include CHERISH, which is testing the drug in later-onset SMA, and NURTURE, for infants with a genetically confirmed diagnosis of SMA who are not yet showing symptoms.

MDA supported early development of nusinersen

MDA has funded foundational work in SMA and invested nearly $750,000 in awards to Adrian Krainer, professor of molecular genetics at Cold Spring Harbor Laboratory in New York, for early-stage development of nusinersen. Since its inception, MDA has invested more than $45 million in SMA research.

FDA approval of the NDA would allow widespread access to nusinersen for kids with SMA across the United States and make the drug the first FDA-approved treatment for the life-threatening disease.

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