10 August 2020 - - The US Food and Drug Administration has approved Evrysdi (risdiplam) for treatment of spinal muscular atrophy in adults and children 2 months of age and older, US-based biotechnology company Genentech said.

Genentech, a member of Switzerland's Roche Group (SIX: RO) (OTCQX: RHHBY).

Evrysdi showed clinically-meaningful improvements in motor function across two clinical trials in people with varying ages and levels of disease severity, including Types 1, 2, and 3 SMA.

Infants achieved the ability to sit without support for at least 5 seconds, a key motor milestone not normally seen in the natural course of the disease. Evrysdi also improved survival without permanent ventilation at 12 and 23 months, compared to natural history.

A liquid medicine, Evrysdi is administered daily at home by mouth or feeding tube.

Evrysdi is being studied in more than 450 people as part of a large and robust clinical trial program in SMA.

The programme includes infants aged two months to adults aged 60 with varying symptoms and motor function, such as people with scoliosis or joint contractures, and those previously treated for SMA with another medication.

The approval is based on data from two clinical studies designed to represent a broad spectrum of people living with SMA: FIREFISH in symptomatic infants aged 2 to 7 months; and SUNFISH in children and adults aged 2 to 25 years.

SUNFISH is the first and only placebo-controlled trial to include adults with Types 2 and 3 SMA.

In FIREFISH, 41% of infants treated with the therapeutic dose achieved the ability to sit without support for at least 5 seconds as measured by the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III).

Additionally, 90% (19/21) of infants were alive without permanent ventilation at 12 months of treatment and reached 15 months of age or older.

As described in the natural history of untreated infantile-onset SMA, infants would not be expected to be able to sit independently, and only 25% would be expected to survive without permanent ventilation beyond 14 months of age.

In SUNFISH, children and adults treated with Evrysdi experienced a clinically-meaningful and statistically-significant improvement in motor function at 12 months (1.55 point mean difference; p=0.0156) compared to placebo (1.36 points [95% CI: 0.61, 2.11]; -0.19 points [95% CI: -1.22, 0.84], respectively), as measured by a change from baseline in the Motor Function Measure-32 (MFM-32) total score.

Evrysdi demonstrated a favorable efficacy and safety profile, with the safety profile established across the FIREFISH and SUNFISH trials.

The most common adverse reactions were fever, diarrhea, and rash in later-onset SMA.

In infantile-onset SMA, the most common adverse events were similar and also included upper respiratory tract infection, pneumonia, constipation, and vomiting.

There were no treatment-related safety findings leading to withdrawal from either study.

Evrysdi is designed to treat SMA by increasing production of the survival of motor neuron protein. SMN protein is found throughout the body and is critical for maintaining healthy motor neurons and movement.

Genentech leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Evrysdi will be available in the United States within two weeks for direct delivery to patients' homes through Accredo Health Group Inc., an Express Scripts specialty pharmacy.

Genentech is committed to helping patients access the medicines prescribed by their physician.

For people with SMA, the MySMA Support programme team is available to answer questions, provide product education and help families understand insurance coverage and navigate appropriate financial assistance options to start and stay on Evrysdi.

Evrysdi is a survival of motor neuron 2 splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency. Evrysdi is administered daily at home in liquid form by mouth or by feeding tube.

Risdiplam was granted PRIME designation by the European Medicines Agency in 2018 and Orphan Drug Designation by FDA and EMA in 2017 and 2019, respectively.

At this time, risdiplam has been filed in Brazil, Chile, China, Indonesia, Russia, South Korea, and Taiwan. A Marketing Authorization Application submission to the EMA for Evrysdi is imminent.

FIREFISH, an open-label, two-part pivotal study, was designed to assess Evrysdi safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics in patients aged 1 to 7 months with Type 1 SMA. Part 1 evaluated several doses of Evrysdi and determined the therapeutic dose of 0.2 mg/kg for Part 2.

Evrysdi is a prescription medicine used to treat spinal muscular atrophy in adults and children 2 months of age and older.

Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, stroke, neuromyelitis optica spectrum disorder, Alzheimer's disease, Huntington's disease, Parkinson's disease, Duchenne muscular dystrophy and autism spectrum disorder.