Teva officials said last month that their migraine drug fremanezumab, a linchpin of their growth plans, might not be delayed by "limited" problems at the Celltrion plant where its active ingredient would be made. But experts say those problems probably aren't as limited as Teva might have hoped.
After reviewing FDA warnings issued to Celltrion, a drug manufacturing specialist told Leerink that the agency cited issues that likely extend beyond the plant's fill/finish operations, the firm said in an investor note. The Celltrion facility would be Teva's main API supplier for fremanezumab.
“The specialist believes that while the inspection that resulted in the Form 483 and Warning Letter was done only at the fill/finish part of the facility, many of the observations cited, particularly around data integrity, could be present at the API manufacturing part of the facility as well,” the Leerink analysts said.
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And that means Teva's likely to face a delay in rolling out fremanezumab until mid-2019, the analysts wrote.
“The specialist believes that as long as Teva continues to source fremanezumab's API from the Celltrion facility with an outstanding Warning Letter, it is very unlikely the FDA will approve the product,” the note stated.
Although Teva has said it plans to source the API from another manufacturer, Leerink's analysts contended that switching API suppliers isn’t “a near-term option” and that the only successful path to gaining FDA approval for fremanezumab “is the resolution” of the issues at the Celltrion facility.
In announcing the potential delay in February, Teva CEO Kåre Schultz noted that the company is in talks with the FDA to determine how Celltrion's problems might affect its fremenezumab approval application, pointing out that the inspection focused on the facility's fill-finish operations. “It could take six to 18 months to resolve a warning letter, but we are having API made there, and that is not affected by the warning letter, so an approval could be sooner, but we don’t know,” Shultz said on the company's fourth-quarter earnings call with analysts.
The forecast comes as Teva announced it decided not to continue to develop and commercialize lead candidate HTL0022562 and other novel small molecule CGRP antagonists for the treatment of migraine and other severe headache, under an agreement with Japan’s Sosei Group.
The FDA posted the Celltrion warning letter last month, recommending that the South Korean-based drugmaker consider hiring outside experts to help it get its production in order. The letter criticized the facility for poor practices in its aseptic fill area and ordered the company to do a retrospective assessment of all media fills for the last four years. It also cited problems with the plant’s investigation of visible particles in finished drug products that were bound for the U.S., among other issues.
Teva has said it expects to have more control over its biologics manufacturing in the future at a plant it is building at its site in Ulm, Germany. Teva is moving forward with that project—which is slated to be completed in 2020—even as the drugmaker has launched a $3 billion cost-cutting plan that will shutter up to 25 other manufacturing plants in the next two years.