In the first complete response letter of 2017, the FDA has asked Boston-area biotech Tesaro for more information about manufacturing by its two contractors, a move that has delayed consideration of its new intravenous version of Varubi, a treatment for nausea and vomiting from chemotherapy.
Waltham, MA-based Tesaro Wednesday pointed out that the FDA is not asking for more clinical trials and did not raise concerns about the API being used in the drug candidate. Tesaro has a different supplier for its API than for the finished product. Instead it wanted more information about the in vitro method utilized to demonstrate comparability of the rolapitant IV produced at its two proposed commercial sterile manufacturers.
Tesaro already has an oral form of the drug approved.
In a call with analysts Thursday morning, Mary Lynne Hedley, COO of the oncology-focused Tesaro said the FDA was seeking information on its rationale for the validation used and some additional test results, which the company has in its system. She said the company is responding “expeditiously.”
Based on the questions asked by the FDA, Hedley said that Tesaro expects the FDA to grant it a class I resubmission. That would mean a two-month turn-around, which would allow for an approval of the IV formulation in H1 2017. “We expect to launch immediately after that,” she told analysts.
As way of background, Hedley explained that after Tesaro identified “potential deficiencies” at its original CMO, and so secured a second manufacturer. During the NDA review, the FDA requested in vitro data to demonstrate comparability of drug product made at the two manufacturing sites, which Tesaro provided.
In response to analyst questions, Hedley said its original supplier is still under review by the FDA and Tesaro expects to get its drug supply from its second supplier.
Given the number of complete response letters that have recently been tied to manufacturing concerns, one analyst asked Hedley if the FDA seems to be giving a “sharper focus” to chemistry, manufacturing and control (CMC) issues during new drug reviews.
“We have noticed the number of CRLs related to CMC issues, but we have no insight into those others,” Hedley said, “We wish we would have been able to have had those conversions in the course of the review, but the FDA chose the path they have taken and we will deal with that.”
In fact, of the 14 CRLs issued last year, five were related primarily to CMC issues, 36%. Another at the end of the year, included CMC issues, as well as safety concerns. That compares to only four out of 47 CRLs between 2010 and 2015. One of those went to Sanofi and Regeneron for problems at a Sanofi fill/finish plant. Sanofi this week announced it believed the issues were resolved, and that a re-inspection and approval will soon happen.
FDA spokesperson Kristofer Baumgartner has said that while the number of CRLs related to manufacturing is higher than in recent years, it is not because the FDA is conducting a more rigorous review of CMC processes during new drug reviews. Instead he said the increase “is related to the types of applications and their complexities.”
Leerink estimates worldwide Varubi sales in 2026 at $343 million, with the majority of this coming from the U.S.
Editor's Note: The story was updated to include a peak sales forecast.