Genentech’s Spinal Muscular Atrophy Therapy Shows Significant Improvement in Motor Function

Edward Kim  |

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Image: Spinal Muscular Atrophy Foundation

Spinal muscular atrophy (SMA) is a progressive genetic disease that causes devastating muscle atrophy and disease-related complications. SMA is the leading genetic cause of death in infants and toddlers, according to the Spinal Muscular Atrophy Foundation. The disease has generally been believed to be one of the most common among the "rare" diseases, affecting as many as 10,000 to 25,000 people in the US.

According to the National Human Genome Research Institute, part of the National Institutes of Health (NIH), one in 6,000 to one in 10,000 children are born with the disease. SMA is an autosomal recessive genetic disease, meaning that a person requires two copies of the defective gene to have the disease. If both parents are carriers of the defective gene, then each of their children has a 25% chance of developing SMA. One in 50 people are carriers.

The disease is caused by defects in the Survival Motor Neuron 1 (SMN1) gene that encodes the SMN protein, which is critical to the health and survival of motor neurons in the spinal cord responsible for muscle contraction.

There are several types of SMA that vary in severity and time of onset.

While SMA patients lack the functional SMN1 gene, they do have the SMN2 gene, or what the SMA Foundation refers to as a "backup gene." SMN2 also encodes for SMN protein, but at greatly reduced efficiency, leading to lower than normal levels of the protein. According to the SMA Foundation, the majority of drug development efforts are focused on increasing SMN protein production from SMN2.

Genentech, a member of the Roche Group, today presented 1-year data from the pivotal 180-patient Part 2 of a global placebo-controlled study called SUNFISH, evaluating risdiplam in people aged 2-25 years with Type 2 or 3 SMA. The study showed that the change from baseline in the primary endpoint of the Motor Function Measure 32 scale (MFM-32) was significantly greater in people treated with risdiplam, compared to placebo (1.55 point mean difference; p=0.0156). MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders.

The Revised Upper Limb Module (RULM), a key secondary endpoint, also showed an improvement (1.59 point difference; p=0.0028).

Data were presented at the 2nd International Scientific and Clinical Congress on Spinal Muscular Atrophy in Evry, France.

SUNFISH is the first placebo-controlled trial to include adults with SMA, and the study demonstrates that risdiplam improved or stabilized motor function in these adults.

As anticipated, exploratory subgroup analyses showed that the strongest responses were observed in the youngest age group (2-5 years) (78.1% with risdiplam vs. 52.9% with placebo, achieving at least a 3 point increase). Importantly, disease stabilization was observed in the 18-25 years age group (57.1% vs. 37.5%, with stabilization defined as at least some increase), which is the goal of treatment for those with more established disease.

Roche obtained an exclusive worldwide license to PTC Therapeutics' SMA program in 2011. PTC had developed the program in conjunction with the SMA Foundation, which has remained active in the collaboration.

Risdiplam is designed to increase and sustain SMN protein levels both throughout the central nervous system and in peripheral tissues of the body. Genentech is evaluating risdiplam in four staged multicenter trials for its potential ability to help the SMN-2 gene produce more functional SMN protein throughout the body:

In November 2019, the FDA granted Priority Review for risdiplam, with an expected decision on approval by May 24, 2020. Today's release of the SUNFISH data only adds to the already promising case for approval.

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In January 2020, Reuters reported that Roche intends to undercut the existing SMA therapies that have been approved, Biogen's Spinraza—priced at $750,000 for the first year and $375,000 for each successive year—and Novartis’s Zolgensma—priced at $2.1 million for what is believed to be a one-time cure.

According to Reuters, Roche CEO "Bill Anderson said the Basel-based company will price the drug much as it did its hemophilia A medicine Hemlibra in 2017, when it undercut traditional therapies made by rivals NovoNordisk and Takeda to help win patients. 'With Hemlibra, we priced at about half of [the competition],' Anderson said in an interview at the JP Morgan Healthcare Conference in San Francisco. 'We aim to underwhelm with our price' with risdiplam."

Reuters cited that analysts see risdiplam topping $1 billion in annual sales for Roche.


Edward Kim is Managing Editor of


Sources: Equities News

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