FDA shoots down petition to stall generic versions of Bristol Myers' blockbuster chemo Abraxane
Five years after Bristol Myers Squibb’s Celgene filed a petition with the FDA as part of an attempt to delay the launch of generic versions of its blockbuster chemo Abraxane, the agency has finally, and almost completely, rejected the petition.
Although Celgene in 2018 (prior to the Bristol Myers’ acquisition) settled with Teva’s Actavis, allowing at least one Abraxane generic to enter the market on March 31, 2022, the company in 2015 sent over a petition to the FDA, seeking to add new requirements for any companies looking to make copycats of its treatment for breast cancer, NSCLC and pancreatic cancer, among other cancers.
For instance, Celgene requested that, in addition to the current in vitro characterization tests recommended in FDA’s paclitaxel draft guidance, the agency include additional in vitro tests and certain functional attribute tests that Celgene said are necessary to ensure product quality and demonstrate sameness. The petition also asserts that clinical immunological assays should be required of any application referencing Abraxane, which brought in more than $1.2 billion for Bristol Myers last year.
Celgene further called on the FDA to revise its paclitaxel draft guidance, but the agency, in its response from June 30, demurred. Historically, the agency has lamented the fact it must use considerable time and effort to respond to such petitions, when the companies issuing them often are only doing so as part of a wider attempt to block competition for their lucrative products.
“Even if the Agency adopted the changes to its Paclitaxel draft guidance urged in the Petition, ANDA applicants would be free to use an alternative approach that satisfies requirements in applicable statutes and regulations,” the agency said.
According to the petition, all three of the proposed generic versions of Abraxane tested in Celgene’s studies — none of which have been approved by FDA — are marketed in India. But FDA says the petition “does not include any data from which FDA could conclude that Celgene’s results are applicable to any product approved by FDA or submitted to FDA for approval in an ANDA or a 505(b)(2) application.”
And based on the limited data reported in the petition, FDA says, all three foreign-sourced paclitaxel products likely would not be eligible for approval under the FDA’s 505(j) pathway for generics and follow-on drugs.
But FDA does agree with one requested revision to the paclitaxel draft guidance to clarify the definition of “free” and “bound” paclitaxel or albumin. “Specifically, ‘fraction of free and bound paclitaxel or albumin in reconstituted suspension’ should be revised to ‘fraction of free (in solution) and particle-bound paclitaxel and albumin in reconstituted suspension,'” FDA said.
The agency also said it does not agree with the inclusion of Celgene’s requested techniques to characterize a nanomaterial.
“Because the field of nanotechnology and methods to characterize nanomaterials are rapidly evolving, as explained in its guidances, FDA generally recommends the critical quality attributes of the product to be measured and not the analytical methods to measure these attributes,” FDA said.
And the agency said it disagrees with requiring that paclitaxel formulations aiming to be bioequivalent to, or otherwise relying on FDA’s findings of safety and effectiveness for Abraxane, must ensure the tissue distribution and resulting paclitaxel concentrations to the tumor and healthy tissues are bioequivalent to ensure equivalent clinical outcomes.
“In addition, we disagree with the Petition’s contention that clinical studies must always be performed to adequately assess any immunogenicity concerns due to the presence of albumin,” FDA said.