Manufacturing issues hobble Heron's quest to market its long-acting non-opioid painkiller
The C-suite at Pacira likely sighed in relief on Wednesday, as their main rival, Heron Therapeutics, was handed an unexpected FDA rejection — related to manufacturing concerns — for a competing long-acting non-opioid painkiller for post-surgical analgesia.
The health regulator has asked for additional information related to Heron’s chemistry, manufacturing and controls and other non-clinical data — and has not identified any safety or efficacy issues, nor asked for extra clinical studies and data analyses for the drug, HTX-011, Heron said.
Pacira investors cheered the announcement, lifting the company’s stock $PCRX more than 16% to $46.25 before the bell. Meanwhile, Heron shares $HRTX tumbled more than 26% to $16.01 premarket.
Heron plans to liaise with the FDA to resolve their concerns, and resubmit its marketing application as soon as possible, chief Barry Quart said in a statement.
The manufacturing issues are likely solvable, Cowen analysts wrote in a note, predicting a new FDA decision date in first half of next year.
As the US health regulator persists in its effort to stem the tide of opioid abuse, overdose and addiction while the pharmaceutical architects of the prescription painkiller crisis face fierce scrutiny, Heron Therapeutics had designed the drug to take a bite out of the market that encompasses millions of postoperative patients who are candidates for opioids. HTX-011 has shown in studies to subdue the need for opiates.
Heron is initially targeting roughly 13.5 million patients who have undergone the most painful procedures (typically general surgery, OB/GYN and plastic surgery). Many of these patients are first given a local anesthetic like bupivacaine to dull the pain, but the effects only last about six hours or so, therefore doctors tend to prescribe opioids to manage severe pain that can last up to three days (depending on the surgery).
HTX-011 is designed to slowly release its two ingredients: bupivacaine and the non-steroidal anti-inflammatory drug (NSAID) meloxicam over a three-day period.
When you cut through tissue, and sometimes bone, inflammatory cytokines are released. Apart from the inflammation that arises in response, these cytokines change the local PH of the incision, making it more acidic (local anesthetics tend to lose their potency in acidic environments), and enhance the sensitivity of nerve endings so even low levels of pain produce a larger pain transmission to the brain, Quart explained in an interview with Endpoints News ahead of the FDA decision.
“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 that inflammatory process,” Quart said. “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.”
Combining HTX-011 with two over-the-counter oral analgesics (acetaminophen and ibuprofen) has yielded impressive results in helping post-op pain patients remain opioid free in two studies published by Heron this year.
In a 63-patient study, 90% of patients receiving HTX-011 with the OTC analgesic regimen did not require opioids to manage their postoperative pain through 72 hours post hernia surgery, compared to 51%, 40% and 22% of patients receiving HTX-011, bupivacaine and a placebo, Heron revealed in January. Follow up after 28 days showed 81% of patients remained opioid-free.
“We consider these results as compelling, and supporting a best-in-class profile in post-op pain based on significantly more opioid-free patients and substantially lower opioid use. HTX-011 could offer the only option of opioid-free prescription at discharge, which remains a high priority in the battle against opioid abuse,” Jefferies’ Biren Amin wrote in a note that month.
Apart from bupivacaine, HTX-011 will compete with Pacira Pharmaceuticals’ J&J-partnered, long-acting post-op painkiller Exparel, which generated net sales of about $331 million last year. Exparel’s main ingredient is also bupivacaine and the drug has been approved by the US regulator since October 2011 as a treatment for postsurgical analgesia.
In a note published in March, SVB Leerink analysts wrote that while “Exparel does a good job reducing opioid use for post-op pain; HTX-011 could do this better,” citing a KOL survey. “…it (Exparel) has done a good job in reducing opioid use and hospitalization time in its post-operative patients, the duration of efficacy is in the 24-36 hour range. As such, this KOL believes the longer potential duration of efficacy and the instillation method of HTX-011 will result in initial use of the product. But upon availability of both products, this KOL believes hospitals will run their own pilot studies in various surgical models to see how they compare to one another.”
Over half the patients Heron is targeting are receiving bupivacaine, and about 4% are getting Exparel — the rest are getting various “caines” such as lidocaine, Quart said. “While we obviously expect to take a certain part of Exparel market share…our primary target is the 96% of patients who are receiving…short-acting local anaesthetics.”
Pacira, which unveiled plans to swallow a company that makes a system that uses intensely cold therapy on a specific nerve to relieve pain to complement its flagship Exparel treatment and fortify its pain franchise in March, is set to report is first-quarter results on Thursday.
Year-on-year Exparel revenue growth for 2019 is estimated at 23%, Jefferies analysts predicted in a note last week. “(D)espite the strong recent (Exparel) results…current penetration rates remain very low…and the market is certainly large enough to accommodate two or more players. In fact, we think the additional voice of another marketing team raising awareness for non-opioid post-surgical pain options arguably helps all market participants. And perhaps most importantly, we view the situation as less like ‘Coke vs Pepsi’ and more to the point that if unbundling and access continue to improve, all competitors in the segment benefit.”