FDA again rejects Ocular drug over manufacturing failings

FDA
The FDA sent the CRL one day after Ocular tried to delay the PDUFA date

The FDA has hit Ocular Therapeutix with another complete response letter. Officials at the agency again turned down Ocular’s filing for approval of postoperative pain prospect Dextenza over deficiencies in its manufacturing process.

Ocular has been looking down the barrel of another setback since the FDA flagged up problems with its manufacturing processes and analytical testing following a pre-NDA approval inspection in May. On July 10, Ocular filed a response intended to close out the FDA Form 483 and push back the PDUFA date. On July 11, the FDA hit Ocular with a CRL stating it cannot approve the NDA.

That sequence of events sent Ocular’s stock on a rollercoaster ride, first rising 17% during the day on the back of the attempt to delay the PDUFA date, before plummeting 32% after hours following news of the CRL. The sinking of the stock has implications for the viability of Ocular, which had $80 million in the bank at the end of March having burnt through $15 million in the preceding quarter. 

Ocular plans to work with the FDA to get the filing back on track but precedent suggests the time that takes may swallow up its financial runway. Prior to the CRL, Ocular said its cash would see it through the second quarter of next year. When Ocular last received a CRL, it took six months to resubmit the NDA and a further six months to learn the FDA’s decision.

In its favor, Ocular thinks it has already taken actions needed to fix the manufacturing problems. The FDA was unable to review Ocular’s attempt to close out the Form 483 and extend the PDUFA date before sending the CRL. Ocular can use the materials it submitted on July 10 to respond to the shortcomings highlighted in the CRL.

While that potentially gives Ocular an abbreviated route to fixing the CRL, every delay further diminishes the prospects of a product that already looked like having to scrap for market share. Dextenza is an extended-release formulation of dexamethasone designed to replace the eye drops patients use to manage pain after cataract surgery.

Questions about how much payers are willing to pay for Dextenza when well-established products exist—and what proportion of patients would prefer an intracanalicular insert to eye drops—have dogged the candidate throughout development. And the initial market targeted by Ocular shrank after a failure in phase 3 forced it to go after pain first and leave inflammation for a later filing.  

Since then, Ocular has chalked up two manufacturing-related CRLs. That makes it part of a trend that started last year and has continued into 2017. Last year, five of the dozen CRLs issued by the FDA related to manufacturing. In 2014 and 2015, the FDA issued one manufacturing-related CRL a year. This year picked up where 2016 left off. Ocular joins AstraZeneca, Sun Pharma and Tesaro on the list of drugmakers to receive manufacturing-related CRLs this year.