FDA Rejects Tanvex's Proposed Filgrastim Biosimilar, TX01

The FDA has issued a complete response letter (CRL) for Tanvex BioPharma’s TX01, a proposed biosimilar filgrastim referencing Neupogen.

Tanvex said in a statement that the FDA did not request additional clinical data or express concerns about the product’s safety, and the company said it plans to resubmit its Biologics License Application (BLA) to the FDA as soon as it has addressed items raised by the regulator.

Included in the data package in the product’s BLA were findings from 3 studies of the biosimilar versus its reference.

The first study was a single-dose, randomized, double-blind, crossover study that assessed the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of the biosimilar versus the reference. The 90% confidence intervals (CIs) of the PK and PD parameters fell within the prespecified equivalence margin, says Tanvex; the 90% CI of the ratio of the mean of the biosimilar versus the reference was contained within 80% to 125%.

The second study was a multiple-dose, randomized, double-blind crossover study to assess PD, immunogenicity, and safety of the biosimilar versus the reference. Fifty healthy volunteers were enrolled in this trial, and the PD parameters once again met the prespecified equivalence margin described above. The biosimilar was associated with adverse events that are part of the known safety profile of filgrastim. The incidence of antidrug antibodies (ADAs) was similar between patients receiving both treatments, and ADAs were of a low titer.

Finally, the third study, a multiple-dose, randomized, double-blind, parallel study comparing the biosimilar and the reference, had immunogenicity as its primary end point. In 220 healthy volunteers, ADAs were noted, but were of low titer, were transient, and were not neutralizing. The upper bound of the 1-sided 95% CI of the ADA rate difference between the biosimilar and the reference was lower than the prespecified noninferiority margin.

In addition to this regulatory setback, Tanvex has faced legal challenges related to the biosimilar. In July of this year, Amgen sued Tanvex and 2 of its affiliates for allegedly infringing on a patent that covers the folding of proteins. In its complaint, Amgen asked the court for a declaratory judgment of infringement, a preliminary or permanent injunction barring Tanvex from infringing on the patent, and damages. Tanvex filed its response to Amgen last month, including defenses and counterclaims of noninfringement and invalidity.

Tanvex has also submitted the biosimilar for regulatory approval in Canada, and the product is currently under review.