1 March 2021 - - The European Medicines Agency Committee for Medicinal Products for Human Use has recommended the approval of Evrysdi (risdiplam) for the treatment of 5q spinal muscular atrophy in patients two months and older, with a clinical diagnosis of SMA Type 1, Type 2 or Type 3 with one to four SMN2 copies, US-based PTC Therapeutics, Inc. (NASDAQ: PTCT) said.

The CHMP review was completed under the accelerated assessment pathway, which is offered to medicines deemed to be of major interest for public health and therapeutic innovation.

The CHMP recommendation is based on data from the FIREFISH study in infants aged 2 to 7 months with symptomatic Type 1 SMA and the SUNFISH study in children and young adults with Type 2 or 3 SMA.

The two pivotal studies were designed to represent a broad spectrum of people living with SMA, and SUNFISH is the first and only placebo-controlled trial to include adults with Types 2 and 3 SMA.

A final decision regarding approval is expected from the European Commission in the next two months and will be applicable to all 27 European Union member states, as well as Iceland, Norway, and Liechtenstein.

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

More than 2,500 patients have now been treated with Evrysdi in clinical trials, compassionate use programs and real-world settings, with patients ranging from birth to over 70 years old including those previously treated with other SMA therapies.

Evrysdi has been approved in seven countries thus far including the US, Chile, Brazil, Ukraine, South Korea, Georgia and Russia. Evrysdi is under review in a further 30 countries including Japan and China.

Evrysdi is based on PTC science and is commercialized in the United States by Genentech, a member of the Roche Group. Roche leads the clinical development of Evrysdi as part of a collaboration with the SMA Foundation and PTC Therapeutics.

Spinal muscular atrophy is a severe, progressive neuromuscular disease that can be fatal. It affects approximately 1 in 10,000 babies and when untreated is the leading genetic cause of infant mortality.

SMA is caused by a mutation of the survival motor neuron 1 gene, which leads to a deficiency of SMN protein.

This protein is found throughout the body and is essential to the function of nerves that control muscles and movement.

Without it, nerve cells cannot function correctly, leading to progressive muscle weakness over time. Depending on the type of SMA, an individual's physical strength and their ability to walk, eat or breathe can be significantly diminished or lost.

Evrysdi is a survival motor neuron 2 -directed RNA splicing modifier designed to treat SMA caused by mutations in chromosome 5q that lead to SMN protein deficiency.

Evrysdi is designed to distribute evenly to all parts of the body, including the central nervous system. Evrysdi is administered daily at home in liquid form by mouth or feeding tube.

The US Food and Drug Administration recently approved Evrysdi (risdiplam) for the treatment of spinal muscular atrophy for adults and children 2 months and older.

Evrysdi (risdiplam) is marketed in the United States by Genentech, a member of the Roche Group.

FIREFISH (NCT02913482) is an open-label, two-part pivotal clinical trial in infants with Type 1 SMA. Part 1 was a dose-escalation study in 21 infants with the primary objective of assessing the safety profile of risdiplam in infants and determining the dose for Part 2.

Part 2 is a pivotal, single-arm study of risdiplam in 41 infants with Type 1 SMA treated for two years followed by an open-label extension.

The primary objective of Part 2 was to assess efficacy as measured by the proportion of infants sitting without support after 12 months of treatment, as assessed in the Gross Motor Scale of the Bayley Scales of Infant and Toddler Development - Third Edition (BSID-III) (defined as sitting without support for five seconds). The study met its primary endpoint.

SUNFISH (NCT02908685) is a two part, double-blind, placebo controlled pivotal study in people aged 2 to 25 years with Types 2 or 3 SMA. Part 1 determined the dose for the confirmatory Part 2.

Part 2 (n=180) evaluated motor function using the Motor Function Measure 32 (MFM-32) scale at 12 months. MFM-32 is a validated scale used to evaluate fine and gross motor function in people with neurological disorders, including SMA. The study met its primary endpoint.

The safety profile of Evrysdi was established across FIREFISH and SUNFISH pivotal trials. The most common adverse reactions in later-onset SMA (incidence of at least 10% of patients treated with Evrysdi and more frequently than control) were fever, diarrhea, and rash.

The most common adverse reactions in infantile-onset SMA were similar to those observed in later-onset SMA patients.

Additionally, the most common adverse reactions (incidence of at least 10%) were upper respiratory tract infection, pneumonia, constipation, and vomiting.

PTC Therapeutics is a biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders.