UPDATED: Catalent issues lead to CRL for OPKO

Miami-based OPKO said on Wednesday that it has received a complete response letter for a drug it hopes to launch this year. But the reason for the CRL had nothing to do with the safety, efficacy or labeling of the drug. Instead, OPKO execs say, it was laid entirely at the feet of Catalent ($CTLT), the contract manufacturer that is manufacturing OPKO's candidate.

The CRL followed an FDA inspection of a Catalent plant in St. Petersburg, FL, that resulted in a Form 483 being issued last week. In fact, OPKO said in its announcement, the CRL was not specific to the manufacturing of Rayaldee, OPKO's treatment for secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. In a conference call, OPKO CEO and biotech billionaire Dr. Phillip Frost told analysts the observations were general in nature.

"We were quite surprised to receive this response which was based entirely on deficiencies observed at the third party contract manufacturing organization we engaged to manufacture Rayaldee," Frost said. "Without the problems at the Catalent plant, we are sure Rayaldee would have been approved."

Catalent wouldn't speak to the number or nature of the observations, but a spokesperson said, "Catalent has already begun to address the observations and is preparing a comprehensive written response that will be submitted to the FDA by April 15, 2016. The St. Petersburg facility was previously inspected by the FDA in December 2013 with only one observation, and has since had many other successful inspections and new product approvals from multiple regulatory agencies."

OPKO EVP Steve Rubin said on the call that neither Catalent nor OPKO were aware of any deficiencies until the Form 483 was issued. Catalent has assured OPKO it is preparing a robust response to the FDA and OPKO will soon resubmit its NDA for Rayaldee, he said. Depending on whether the FDA requires a reinspection, Rubin said OPKO expects it will take 2 to 6 months to resolve the issues. He said a Q2 2016 launch of the drug was always planned and that is still what execs expect.

This kind of CRL and delay is not unprecedented and has not always been resolved quickly. Allergan ($AGN) received a CRL from the FDA in 2014 delaying approval of migraine drug Semprana because of manufacturing concerns. That CRL followed one in 2012 that Map Pharmaceuticals received for the drug before Map was acquired by Allergan. The same thing happened to Valeant Pharmaceuticals ($VRX) in 2013 over efinaconazole, its topical treatment for onychomycosis; Valeant got approval more than a year later. Impax Laboratories ​($IPXL) took about four years to resolve FDA issues over two plants before getting its Parkinson's disease drug Rytary approved last year.

This matter arises for Catalent even as the Somerset, NJ-based company has been dealing with issues in France where a plant in Beinheim had to be taken offline for four months because Catalent had concerns that someone inside the facility was sabotaging products. Catalent, with the approval of French regulators, restarted the facility last month after beefing up security and limiting access to production. The production interruption, however, led GlaxoSmithKline ($GSK) to delay the launch in Japan of Zagallo (dutasteride) for alopecia.

- here's the OPKO release
- access the conference call here

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