On April 25 local time, Biogen/lonis jointly announced that FDA has agreed to accelerate the approval of antisense oligonucleotide therapy tofersen for the treatment of amyotrophic lateral sclerosis (ALS) caused by superoxide dismutase 1 (SOD1) mutation. This is the first gene targeting therapy for ALS.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease known as the "top five incurable diseases worldwide". ALS is a relatively niche type of motor neuron disease, with a prevalence rate of approximately 4-6/100000 people previously reported internationally. There are nearly 30000 ALS patients in the United States alone, and due to the large population base in our country, the number of patients cannot be ignored. The average survival period of ALS patients is only 2-5 years, while in Europe and America it is only 2-3 years. At present, the cause of ALS is still unclear, with only 5% -10% of patients having clear genetic factors. ALS patients often experience systemic paralysis and inability to speak in the late stages of the disease, as if their bodies have been "frozen", hence commonly known as "progressive frostbite". Famous physicists such as Huo Jin, director of Wuhan Jinyintan Hospital Zhang Dingyu, and JD Vice President Cai Lei are all ALS patients.
Tofersen is an antisense drug developed by Ionis for the treatment of superoxide dismutase 1 (SOD1) ALS. It can combine with the mRNA encoding SOD1 and be degraded by ribonuclease RNase-H, thereby reducing the production of mutant SOD1 protein. Biogen obtained tofersen's license from Ionis under a collaborative development and licensing agreement.
In July 2022, the FDA accepted the product's marketing application and granted priority review qualifications, setting the PDUFA date as January 15, 2023; In October of the same year, Biogen announced that the FDA had postponed the approval process and the PDUFA had been extended for three months until April 25, 2023.
The approval for listing this time is mainly based on the research results of Phase I clinical trials, Phase I/II multi dose ramp up (MAD) clinical trials, Phase III clinical trials of VALOR, and Open Label Extension (OLE) in healthy volunteers, as well as the integration results of nearly 12 months of VALOR and OLE studies.
The previously published key Phase III VALOR study did not reach the main endpoint, and there was no significant statistical difference (p=0.97) in the revised version of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score from baseline to week 28 among the population with rapid progress.
As of now, the FDA has approved four drugs for the treatment of ALS. In addition to the recently approved tofersen, the other three drugs are Liluzole, Edaravone, and Relyvrio, which were approved in the 1990s, 2017, and 2022.
