Executive Summary

In citizen petition response involving Takeda’s Velcade, agency says ANDA and 505(b)(2) applicants may add more words to the indication statement in order to carve-out protected uses from the reference product’s broadly written indication.

The US FDA appears to have established a new “carve in” approach to “carving out” a reference product’s protected uses from generic drug labeling in its recent response to a Takeda Oncology citizen petition on Velcade (bortezomib).

Velcade is currently indicated for treatment of patients with multiple myeloma and mantle cell lymphoma. These indications have been broadened over time from their initial claims, which covered multiple myeloma patients who received at least two prior lines of therapy and second-line treatment of mantle cell lymphoma.

The current indications encompass retreatment with bortezomib in multiple myeloma and first-line treatment of mantle cell lymphoma; Takeda still holds various exclusivities on these uses and the supporting data.

In a June petition, Takeda requested FDA not approve any abbreviated new drug application (ANDA) or 505(b)(2) new drug application (NDA) for bortezomib if labeling omits protected information regarding retreatment in multiple myeloma patients or first-line mantle cell lymphoma. Carving out these uses would raise safety and efficacy issues related to the non-protected uses and should not be permitted, Takeda asserted.

“We do not believe it would be appropriate for the scope of exclusivity for Velcade to be broadened due to the writing of labeling in a clear and concise manner.” – FDA

However, in a Nov. 6 response, FDA said that omitting the protected multiple myeloma retreatment information and the protected first-line mantle cell indication would not adversely affect efficacy or safety in the remaining indications.

In addition, FDA concluded that retaining only the second-line mantle cell indication was permissible under its carve-out authority even if “the only way to omit the protected indication is to add words” because of the way the Velcade indication is currently worded.

When FDA approved the drug’s first-line use in mantle cell, it consolidated the first- and second-line indications into a single statement – treatment of patients with mantle cell lymphoma. “We do not believe it would be appropriate for the scope of exclusivity for Velcade to be broadened due to the writing of labeling in a clear and concise manner,” FDA said. “Further, we think this is consistent with our past practice.”

‘Minimal Changes’

Even assuming that Takeda is correct in arguing that only de minimis changes are permitted in an ANDA’s labeling, “FDA would consider the change from ‘treatment of patients with mantle cell lymphoma’ to ‘treatment of patients with mantle cell lymphoma who have received at least one prior therapy’ to be appropriate,” the agency said.

“FDA believes that changes are de minimis if they are minimal changes made only to carve out the protected indication,” the response states. “Although labeling language appropriately describing the indication not protected by exclusivity would be the same as the earlier version of Velcade’s labeling, it does not ‘reference discontinued or superseded labeling,’ as the petition argues. Instead, that labeling language is what remains when the protected indication is carved out.”

Industry lawyers are using the phrase “carve in” to describe FDA’s approach to labeling for bortezomib products that reference Velcade.

“FDA – apparently for the first time ever – ruled that the agency will allow a generic drug manufacturer to ‘carve-up’ brand-name labeling and ‘carve-in’ to generic drug labeling a condition of use that no longer appears in brand-name labeling,” Kurt Karst, a director at Hyman, Phelps & McNamara, wrote in an FDA Law Blog post.

FDA’s petition response was innovative in that it allows ANDAs referencing Velcade ” to use more words, not just to omit words,” Marc Scheineson, a partner at Alston & Bird, said at the recent Friends of Cancer Research annual meeting.

Scheineson made the remarks during a panel discussion on challenges to cross-labeling products used as part of a combination therapy regimen. (See sidebar for related story.)

FDA issued the citizen petition response the same date it approved Fresenius Kabi AG’s 505(b)(2) NDA for bortezomib.

https://pink.pharmaintelligence.informa.com/PS122041/Indication-Carve-I…