Team Behind Evrysdi Win 2 Prestigious ‘Drug Discovery’ Awards

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The team of researchers who discovered and developed Evrysdi (risdiplam) — the first at-home oral therapy for spinal muscular atrophy (SMA) — was selected as the winner of two prestigious treatment discovery awards.

These are the Society for Medicines Research (SMR)’s 2021 Award for Drug Discovery and the British Pharmacological Society (BFS)’s 2022 Drug Discovery of the Year award.

Both were established to recognize outstanding contributions, achievements, and inventions in the world of treatment discovery and development that lead to the approval of innovative medicines addressing an unmet medical need.

The SMR prize, awarded every three years, was announced at the society’s recent meeting, held virtually Dec. 2. The BFS award will be given during its annual meeting, Pharmacology 2022 , taking place in the U.K. on Sept. 13–14. At this conference, the team behind Evrysdi will also have the chance to present its work.

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“We are honored to have Evrysdi recognized by these awards,” Stuart W. Peltz, PhD, CEO of PTC Therapeutics, one of the treatment’s developers, said in a press release.

“More importantly, we are most thrilled by the transformative impact this oral therapy has had on people living with SMA,” Peltz added.

Evrysdi, a small molecule approved in more than 60 countries as an SMA treatment, was developed by Roche and its subsidiary Genentech in collaboration with PTC Therapeutics and the SMA Foundation.

The therapy works by increasing the levels of SMN, a protein essential for motor neuron and muscle health and whose production is impaired in people with SMA.

Specifically, it targets the intermediate RNA molecule used as a template for SMN production in a way that prevents an event called alternative splicing that reduces the generation of a full-length SMN protein.

“Traditional small molecule medicines act to [suppress] or activate the protein target to mediate their therapeutic effects,” Steve Rees, BFS’s elected trustee (industry), said in a separate press release.

“Evrysdi is the first example of an approved small molecule medicine that targets RNA rather than protein to mediate therapeutic efficacy,” Rees added.

This was what made the therapy stand out from the 150 innovative medicines considered for BFS’s 2022 award.

William Pao, head of Roche’s pharmaceutical research and early development, said that “the development story of Evrysdi, the first at home administered small molecule mRNA splicing modifier, shows what the power of innovation, collaboration and passion can do for patients.”

“By thinking out-of-the-box, partnering with PTC Therapeutics and the SMA Foundation, and working across the entire organization, our colleagues have been able to deliver a life-transforming medicine to SMA patients who desperately need it,” Pao added.

“Our journey of modulating splicing by small molecules to treat diseases began more than 15 years ago,” Peltz said, adding that at the time, “the common dogma espoused that it was not possible to identify oral small molecule [medicines] that modified splicing.

“We are excited to see our vision come to fruition, and we are now able to leverage our splicing technology to address multiple other diseases where new treatments are desperately needed,” Peltz said.

Several diseases are caused by mutations that result in abnormal alternative splicing, a natural process that allows for a single gene to give rise to many different proteins.

Much like in a recipe, adding or removing certain key ingredients — in this case, pieces of genetic information called exons — can change the resulting messenger RNA (mRNA) and final protein. (mRNA is a molecule derived from DNA that guides protein production.)

“Evrysdi may pave the way for a new era of oral medicines targeting mRNA for many other diseases,” the BFS stated in its release.

“This is an area of science that will explode in the coming years,” Rees added.

The other two approved therapies for SMA, Biogen’s Spinraza (nusinersen) and Novartis’ gene therapy Zolgensma, also work to increase SMN levels, but their nature and mechanism of action are distinct from those of Evrysdi.

Spinraza is a type of RNA-based molecule called antisense oligonucleotide (ASO) that corrects the same alternative splicing process as Evrysdi, but by targeting different regions in the intermediate mRNA molecule.

Since ASOs are too large to cross a highly selective membrane that prevents large molecules and harmful microorganisms in circulation from reaching the brain, the therapy is given directly into the spinal canal every four months.

Administered through a single infusion directly into the bloodstream, Zolgensma uses a modified harmless virus to deliver a healthy version of SMN1, the mutated gene in SMA, to cells.