FDA Again Dings Heron’s Opioid Alternative Over “Nonclinical Issues”

Xconomy San Diego — 

Heron Therapeutics revealed Monday that its investigational non-opioid drug for treating postoperative pain has again been rejected by the FDA.

The San Diego company’s HTX-011 is an extended-release solution of bupivacaine, a local anesthetic, and meloxicam, a nonsteroidal anti-inflammatory drug. Heron (NASDAQ: HRTX) positioned it as a pain management option that could contribute to a needed reduction in the use of opioid-based medications, which have a high potential for addiction.

According to the company, the FDA’s complete response letter received Friday asked for more information about four “nonclinical” issues. Three relate to excipients—inactive ingredients in a drug formulation—used in preclinical reproductive toxicology studies. The fourth requests a change a manufacturing specification. None relate to clinical safety, efficacy, manufacturing, according to Heron.

“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 during a conference call Monday. “Confirming exposure and changing the specification is a straightforward request and will be accomplished as soon as possible.”

Shares in Heron closed down about 28 percent at $14.26 apiece as of market close Monday.

The experimental drug was first rejected in April 2019, on the grounds the agency needed more manufacturing information. Heron resubmitted its application last September; this February, the FDA extended the March 26 deadline set for its decision by three months. Quart said the FDA hadn’t communicated with Heron since then.

“This is all a surprise to us as of late Friday,” he said.

On the call Evercore ISI analyst Josh Schimmer asked whether Heron thought the pandemic had contributed to the agency’s rejection over issues he characterized as “incredibly minor” relative to the need for alternatives to opioids for pain management.

“We know that the FDA has been overwhelmed with [investigational 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,” Quart said. “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.”

Heron plans to meet with the FDA and resubmit its HTX-011 application “as quickly as possible,” Quart said.

The commercial-stage company has two products, both treatments for chemotherapy-associated nausea and vomiting. HTX-011, if approved, would be its first marketed drug for pain management. It’s also advancing HTX-034, a new iteration of HTX-011; the company began evaluating it in a Phase 1b/2 study in patients undergoing surgery in May.

Quart said the company anticipated reporting about $300 million in cash and equivalents as of the end of the second quarter.

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