Drugs

Sarepta Comments on Golodirsen PSG

Sarepta Therapeutics has submitted comments on an FDA draft product-specific guidance (PSG) for golodirsen intravenous solution, a treatment approved under the accelerated approval pathway for treating Duchenne muscular dystrophy in patients who have a confirmed genetic mutation in the dystrophin gene that is amenable to exon 53 skipping. The company’s comments cover:

The importance of getting it right. As a complex product, it says, golodirsen warrants exacting clinical and scientific assessment of active pharmaceutical ingredient sameness and product bioequivalence to ensure that any purported interchangeable products provide therapeutic equivalence for patients currently receiving the reference-listed drug (RLD). The burden is properly on a generic drug applicant to develop in-depth product comparisons and demonstrate that there are no clinically meaningful differences from the RLD. The approaches outlined in the PSG may not be the full and appropriate list of analytical methods that could be used to characterize the RLD and generics, according to Sarepta. It says the PSG should acknowledge that new information may necessitate revision of data and bioequivalence expectations moving forward.
FDA should publicly address how it will evaluate the equivalence of impurity profiles, including the potential impacts of differences, in the generic antisense oligonucleotide context. To thoroughly evaluate a potential product and its equivalence to the RLD, Sarepta says, a generic drug applicant must provide extensive comparative evaluations of impurities, not only in quantitative totals but also considering a good understanding of impurity characterization and profiling using various techniques.
In vitro comparisons should include evaluation of aggregation and higher order structure formation over product shelf life.
A potential generic must demonstrate a comparable safety profile, expressly including a comparison of immunogenicity.

Sarepta concludes by urging FDA to provide greater clarity on the assessment of active pharmaceutical ingredient sameness based on analytical testing and immunogenicity evaluation to ensure a patient-focused approach so that any generic products coming to market that forego clinical testing do not introduce additional uncertainty or compromise patient safety and efficacy.

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome