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Opioid Drugs

Heron Receives 2nd Rejection Letter from FDA

— July 16, 2020

Drug development company is determined, despite second rejection, to get pain management drug approved.

Heron Therapeutics received a letter from the Food and Drug Administration (FDA) rejecting drug HTX-011, a long-acting formulation of a bupivacaine solution coupled with the anti-inflammatory medication meloxicam.  In several trials the company reported the drug has shown it “can significantly reduce pain intensity and decrease opioid use for 72 hours after surgery.”  The drug is administered using the company’s “:proprietary biochronomer delivery tech,” which Heron also uses in its two injectable therapies, Sustol and Cinvanti, each of which “address one of the primary mechanisms of chemo-induced nausea and vomiting.”

It’s also a non-opioid treatment, making it an attractive option for doctors and regulators combating the opioid epidemic.  The letter, however, marks the second rejection received from the FDA.  According to Heron, in April 2019, the agency originally wanted additional information on chemistry, manufacturing, and controls to proceed, along with more non-clinical data.

Heron Receives 2nd Rejection Letter from FDA
Photo by Christina Victoria Craft on Unsplash

The FDA’s most recent response concerns issues that were “nonclinical and not related to safety or CMC, but rather to four nonclinical issues.”  Three, Heron indicated, concern “confirming exposure of excipients in preclinical reproductive toxicology studies, and the fourth relates to changing the manufacturing release specification of the allowable level of an impurity based on animal toxicology coverage,’

“We do not believe that any of the issues are significant barriers to ultimate approval as all of the excipients have extensive histories of use in pharmaceuticals, and the doses used in the reproductive and toxicology studies of these excipients were very high multiples of the human dose based on body weight,” Heron president and CEO Barry Quart said. “Confirming exposure and changing the specification is a straightforward request and will be accomplished as soon as possible….The Company will request a Type A meeting to obtain agreement with the Agency on our responses and resubmit the application as quickly as possible.”

He added, “We know that the FDA has been overwhelmed with [new drug applications] and protocols related to COVID-19 and that the Division of [Anesthesiology], Addiction Medicine, and Pain Medicine has been actively involved in those efforts; they’ve also had several individuals depart from that division.  We don’t know whether that was related to the lack of dialogue during the review and why these issues came up at the very end, as a surprise.”

HTX-011, if approved, would be Heron’s first marketed drug for pain management and the company is determined to keep pushing forward.

“Adding a small amount of the NSAID meloxicam into our polymer formulation and releasing that simultaneously over three days allowed us to block enough of [the] inflammatory process,” Quart explained. “We can show clear pain reduction for the full three days that the drug (HTX-011) is being released. It’s the first time, that we know of, that an extended-release local anesthetic of any kind regardless of how its delivered has been able to beat bupivacaine solution as standard-of-care in large Phase III trials.’


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