Onasemnogene abeparvovec-xioi (Zolgensma): Approval strategy with manipulated data?

Last Updated on

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 neuronsLoss 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.

Print Friendly, PDF & Email


Tags: , , , , , , , ,
About the Author
thassodotcom Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

Leave a Reply

Optional: Social Subscribe/Login

Notify of

thasso: conditions

thasso: tweets

thasso post: magazine

View my Flipboard Magazine.

thasso: categories

thasso: archives

thasso: simple chat

You must be a registered user to participate in this chat.

  • Descendants of early Europeans and Africans in US carry Native American genetic legacy September 19, 2019
    Many people in the U.S. do not belong to Native American communities but still carry bits of Native American DNA, inherited from European and African ancestors who had children with indigenous individuals during colonization and settlement. In a new study published 19th September in PLOS Genetics, Andrew Conley of the Georgia Institute of Technology and […]
  • IGF1 gene is essential to adult tendon growth, animal study shows September 19, 2019
    Tendon injuries are among the most common injuries seen in athletes at all levels, from weekend warriors to professional basketball players. For those who rupture their tendons, returning to the same level of physical activity they enjoyed before the injury is rare.
  • Researchers create new protocol to improve gene therapy tool production September 19, 2019
    A method to create a faster and lower cost alternative for a gene therapy tool has been developed by Boston University School of Medicine (BUSM) researchers.
  • Genetic variants with possible positive implications for lifestyle September 19, 2019
    A German and British research team lead by Technical University of Munich (TUM) has examined the interplay between genetics, cardiovascular disease and educational attainment in a major population study. Genetic variants which had been linked to educational attainment in other studies were observed in the subjects. The researchers found that these variants also had implications […]
  • Scientists develop new methodology to genetically modify lab mice and human cells September 19, 2019
    A team led by Cedars-Sinai has designed a rapid method to genetically alter laboratory mice and then used this method to produce personalized animal models of pediatric glioma, an aggressive type of malignant brain cancer in children.