Roche's Oral SMA Drug Risdiplam Gains Regulatory Acceptance in China, Challenging Nusinersen's Dominance

By Dopine

On April 23, according to the official website of the Center for Drug Evaluation (CDE), Roche’s marketing application for risdiplam oral powder for solution, a drug for spinal muscular atrophy, was accepted by the CDE. It is reported that in early April, the U.S. Food and Drug Administration (FDA) postponed the PDUFA date for this drug, with a response from the FDA expected by late August this year.

Spinal Muscular Atrophy (SMA) is a hereditary, progressive neuromuscular disease that can lead to devastating muscle atrophy and disease-related complications. It is the leading genetic killer among infants under two years of age, with a prevalence of 1 in 6,000 to 1 in 10,000 live births. There are approximately 30,000 to 50,000 patients with SMA in China.

As a rare disease, spinal muscular atrophy (SMA) has very few approved therapeutic options globally, with only Biogen’s Spinraza and Novartis’s gene therapy Zolgensma currently authorized. Spinraza is an antisense oligonucleotide that modifies SMN2 gene splicing to increase the production of full-length functional SMN protein. It is the first drug approved worldwide for the treatment of SMA. Reportedly, the price in the United States is $125,000 per injection, requiring six doses in the first year, resulting in an annual treatment cost of $750,000. In the second year, the treatment cost is reduced by half to $375,000, making it considerably expensive. Zolgensma, developed by AveXis, Inc. (later acquired by Novartis), is an SMN1 gene replacement therapy and the first SMA gene therapy approved by the FDA. Priced at $2.1 million per dose in the United States, it was once regarded as the “most expensive therapy in history.”

In May 2018, spinal muscular atrophy (SMA) was included in China’s First Batch of Rare Diseases Catalogue. Subsequently, Biogen’s Spinraza (nusinersen), a novel therapy for rare diseases already marketed abroad and urgently needed for clinical use, was incorporated into the priority review and approval process. It has since become the first and, to date, the only SMA treatment approved in China. The drug is indicated for the treatment of 5q spinal muscular atrophy (5q-SMA), the most common form of SMA, accounting for approximately 95% of all cases. This type of SMA is caused by mutations in the SMN1 (survival motor neuron 1) gene on chromosome 5, hence the designation 5q-SMA. Reportedly, the retail price of nusinersen in Beijing is RMB 699,700 per vial (5 mL: 12 mg), with the prohibitive cost deterring many patients from accessing treatment.

Risdiplam is an oral liquid, a survival motor neuron 2 (SMN2) splicing modifier designed to continuously increase and maintain SMN protein levels in the central nervous system and peripheral tissues. After oral administration, it exhibits systemic distribution, sustaining increased SMN protein levels in both the central nervous system and peripheral tissues. It has demonstrated improvements in motor function for patients with Type 1, Type 2, and Type 3 spinal muscular atrophy (SMA). In the United States, the drug was granted orphan drug designation in January 2017 and fast-track designation in April 2017. Upon successful approval, it will become the first oral medication for treating SMA patients. Furthermore, while Spinraza and Zolgensma are both indicated for Type 1 SMA patients, risdiplam holds promise for addressing the population of SMA patients who currently lack treatment options.

Currently, according to the Insight database, three clinical trials of risdiplam have been registered in China, all of which are ongoing. The author speculates that the current marketing authorization application for risdiplam is based on overseas clinical trial data.

With the acceleration of drug approval processes in China in recent years and the increased emphasis on rare diseases, the author anticipates that risdiplam is likely to be included in the priority review program, thereby accelerating its approval and market launch in China. At that time, risdiplam will break the monopoly held by nusinersen in the field of spinal muscular atrophy (SMA) in China and, leveraging its advantage as an oral medication, become a strong competitor.

References:

[1] CDE Official Website

[2] Insight Database

Original Title: Rare Diseases | Nusinersen Faces Competition as Roche Submits Marketing Application for Spinal Muscular Atrophy Drug Risdiplam