Heron's troubled opioid alternative for post-surgery pain takes flight with FDA nod

After a few troubled years in the nest, Heron Therapeutics' opioid alternative for post-operative pain is ready to take flight. 

The FDA on Thursday approved Heron's dual-acting anesthetic Zynrelef, an extended-release combination of the local anesthetic bupivacaine and the anti-inflammatory drug meloxicam. 

The drug has been cleared as a post-surgical analgesic in adults for up to 72 hours after total knee replacement, bunionectomy and groin hernia repair. The company is pitching Zynrelef as an opioid alternative for post-operative pain relief. The drug is applied directly into the surgical site.

In the drug's phase 3 trial, Zynrelef not only decreased patients' need for opioids following surgery versus solo bupivacaine, the current standard of care, but also allowed more patients to go completely opioid-free, the company said in a release.

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Zynrelef is also the first modified-release local anesthetic to be branded as "extended release" by the FDA, given that late-stage trials showed the drug led to significant pain and opioid-use reduction through the first 72 hours after surgery, Heron said. 

Of the roughly 50 million Americans who undergo surgery each year, up to 67% receive opioids to manage their post-operative pain, orthopedic surgeon Alan Rechter, M.D., said in the company's approval announcement. But with the opioid crisis still in full swing, Heron—and doctors—have been hunting for a better option. 

"The dramatic increase in opioid-related deaths last year highlights the significant need for safe, effective and non-addictive options to manage pain that decrease opioid exposure and reduce the need for opioid prescriptions after surgery," anesthesiologist Roy Soto, M.D., added in a statement.

Recognizing that need, the FDA blessed Zynrelef with fast track designation in late 2017 and granted the drug a breakthrough therapy tag in the second quarter of 2018.

But Zynrelef's path to the regulatory finish line wasn't without its hurdles. In May 2019, the company said it had received a complete response letter (CRL) on Zynrelef, then known as HTX-011, asking for additional chemistry manufacturing and controls information. 

CEO Barry Quart at the time said he was “extraordinary disappointed” that the issues hadn't been resolved during the drug's six-month priority review period, adding that the company would look to meet with the FDA and resubmit its NDA as soon as possible.

Heron hit another setback in June 2020, when it received a second CRL tied to four non-clinical issues. 

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Now, Heron expects Zynrelef to soar onto the U.S. market early this summer. "Our existing commercial team will immediately begin working with current accounts to gain formulary access, with full commercial availability expected by July 2021," Quart said in the release.

The drug is already on the market in Europe, where the European Commission in September granted Zynrelef marketing authorization to treat somatic post-operative pain for small- to medium-sized surgical wounds in adults. 

Jefferies analysts previously estimated that Zynrelef would hit $545 million in peak sales if approved with a superiority claim to generic bupivacaine on its label in certain indications.

In the first three months of the year, Heron's approved meds Cinvanti and Sustol, each of which address one of the primary mechanisms of chemo-induced nausea and vomiting, generated $18.5 million and $1.5 million, respectively. All told, the company's oncology franchise reeled in $20 million for the period, versus $25.4 million in 2020's first quarter.