August 13, 2019 – Onasemnogene abeparvovec-xioi (Zolgensma) is an adeno-associated virus vector-based gene therapy indicated for the treatment of pediatric patients less than 2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. It has been approved by the American Food and Drug Administration (FDA) in May of this year. In clinical practice, Onasemnogene abeparvovec-xioi (Zolgensma) is a one-time treatment, which stably delivers a working form of the SMN1 gene, and will have a list price of $2.1 million per treatment, according to Novartis, who acquired AveXis Inc., the product’s manufacturer in 2018.
According to a very recent contribution in GenomeWeb, the FDA has now been informed by AveXis Inc. about a data manipulation issue that could affect the accuracy of the data from the drug’s testing in animals that was used to support its biologics license application. Apparently, the company reported the issue to the FDA after the drug had been approved only, even though it was aware of the problem as early as March of this year. According to FDA however, the drug would still have been approved had the agency known of the issue earlier, although with a delay of unknown duration.
Overall, this is the kind of information that patients, health care providers, and the public do not want to hear. While everybody understands that the development of drugs, particularly of the new types in the fields of gene replacing, gene editing, and/or gene correction are costly, and while patients may desperately wait for before not existing treatment options for often fatal diseases with genetic backgrounds, companies should avoid to use tricks in order to accelerate approval processes. There is no way that at any stage along the way of development of a drug data are manipulated, not even data from the in vitro- and the animal- study periods of development. This is not acceptable conduct, particularly in the light of drugs like Onasemnogene abeparvovec-xioi (Zolgensma), were treatments of patients occur at a very early age and where long range effects (good or bad) of such therapies will only become evident many years later.
That said, SMA represents a group of neuromuscular disorders that result in the loss of motor neurons and progressive muscle wasting, and is a leading genetic cause of death in infants. SMA (Type 1) is due to a defect in the SMN1 gene. SMA is inherited from a person’s parents in an autosomal recessive manner. The SMN1 gene encodes SMN, a protein necessary for survival of motor neurons. Loss of these neurons prevents the sending of signals between the brain and skeletal muscles. Diagnosis is suspected based on symptoms and confirmed by genetic testing.