Spinal muscular atrophy (SMA) is a hereditary autosomal recessive disease affecting areas of the nervous system that control voluntary muscle movement. Mutation in survival motor neuron (SMN) gene causes deficiency of SMN protein. This results in motor neurons to lose control over voluntary muscle movement. SMA is a leading fatal genetic disease among infants; where one infant in 6,000 births is estimated to suffer from SMA. Furthermore, over 10 million people in the U.S. are carriers of SMA gene.
Based on the age of onset and symptoms, spinal muscular atrophy has been classified in four main types: type 1, type 2, type 3, and type 4, and thus the respective markets. Each of these types has a characteristic disease progression and defined mortality rate. Type 1 SMA is the most severe form, and affects infants aged between zero and six months. Approximately 65% of these cases are of type 1 SMA, wherein infants usually do not survive for more than 2 years. Type 2 SMA is a moderate form affecting children aged between six months and eighteen months. Type 3 and 4 are less severe and usually have a normal lifespan. Spinal muscular atrophy is diagnosed by identifying mutation in survival of motor neuron (SMN) gene. Other diagnostic tests include muscle biopsy, electromyogram (EMG), and nerve conduction velocity.
Currently, no cure exists for spinal muscular atrophy, and the treatment is targeted towards symptoms management. Physiotherapy is strongly recommended in early stages of the disease to extend range of motion and improve muscle flexibility. Spinal muscular atrophy drugs pipeline is dry; however, it has three drugs in phase 1, three in phase 2, and one in phase 3 clinical trials. ISIS-SMNRx, an antisense therapy candidate by Isis Pharmaceuticals, is currently under phase 3 studies for treatment of type 1 and 2 SMA. If approved, ISIS-SMNRx would be the only drug available of the treatment of spinal muscular atrophy, creating lucrative opportunity for Isis Pharmaceuticals and Biogen Idec. Phase 3 study is expected to complete in June 2017. The drug is projected to record sales of USD 468.2 million in the U.S. by 2023.
Olesoxime (TRO19622) has completed its phase2/3 trials, and has shown promising results, with potential to effectively treat type 2 and type 3 SMA. Other potential candidates include Olesoxime (TRO19622), LMI070, RO6885247, CK-2127107, scAAV9.CB.SMN and RG3039. Key players with potential therapeutics in clinical trial phase include AveXis, Inc., Cytokinetics, Inc., F. Hoffmann-La Roche Ltd., Novartis AG, and Isis Pharmaceuticals, Inc.