Pain relief has become a touchy subject.
Although the rate of overdose deaths involving prescription opioids decreased 12% between 2021 and 2022, according to the CDC, the ongoing epidemic still claimed the lives of 82,000 Americans in 2022 as synthetic fentanyl ravages the country.
In the wake of the epidemic and regulators’ crackdown on opioid prescriptions, millions of pain patients have been left without a better solution.
“There's a huge need for additional research and development on pain management,” said Paul Howe, chief commercial officer for Protega Pharmaceuticals, which recently won approval for an abuse-deterrent opioid.
The opportunity for drugmakers to develop better pain management alternatives is there — 80 million people are prescribed medication to treat acute pain every year in the U.S., according to Vertex Pharmaceuticals, which is nearing a PDUFA date for a non-opioid pain treatment.
Vertex is among a handful of drugmakers developing non-opioid pain drugs, but the field has hit a few roadblocks. Eli Lilly and Pfizer, for instance, scrubbed their osteoarthritis pain drug in 2021 after regulators gave it a thumbs down.
While companies like Vertex advance new types of pain drugs, other pharmas are looking to improve on the existing treatments.
New approaches
With its FDA decision on Jan. 30, Vertex could be the first drugmaker in decades to gain approval for a new type of pain drug. Its drug suzetrigine is being evaluated for moderate-to-severe acute pain based on three phase 3 and two phase 2 studies. While there’s a lot of excitement about the drug’s potential, it’s not a sure bet.
In its review late last year, ICER concluded that suzetrigine’s effectiveness compared to opioids and NSAIDs was “promising but inconclusive.” The pharma company also released phase 2 data in December for patients with sciatica pain, showing that the drug met its primary endpoint of clinically reducing pain over a 12-week period, but failed to outperform placebo. The results may have been caused by the complexity of managing placebo groups in trials, Vertex said in a press release.
Despite ICER’s characterization and the recent trial results, the drug would mark a milestone in acute pain management.
“The anticipated approval of suzetrigine is so important because if approved, it will be the first and only non-opioid oral pain signal inhibitor, which means that it will be medicine that combines effective pain relief with a favorable safety profile, and it is non-addictive,” a Vertex spokesperson told PharmaVoice via email.
Suzetrigine works by inhibiting the NaV1.8 sodium channel to reduce pain, while opioids block pain signals on opioid receptors.
“The NaV1.8 sodium channel has long been considered the holy grail of drug discovery in pain because it’s known to be directly involved in the transmission of pain signals and is only found in the periphery — not in the brain,” a Vertex spokesperson said. “No one has successfully developed a treatment that selectively targets the NaV1.8 channel in the sensory nerves to treat pain — until suzetrigine.”
If approved, suzetrigine is expected to reach blockbuster status by 2029, with $1.4 billion in sales, according to an estimate from Global Data. And if Vertex is able to expand the label down the line to chronic pain, which impacts roughly 50 million U.S. adults, the potential market reach is even deeper.
“With the anticipated approval of suzetrigine, we believe that we have the opportunity to change the paradigm of acute pain management and establish a new standard of care,” Vertex said.
A better opioid
While some drugmakers chase new drug classes to forge a path in pain management, others are attempting to make opioids safer.
Protega Pharmaceuticals received the green light in October for its severe pain treatment Roxybond, an oxycodone hydrochloride immediate-release tablet that is the only FDA-approved abuse-deterrent version of the opioid. Developed with Protega’s SentryBond technology, the new treatment cannot be manipulated for abuse through crushing, injecting or snorting.
“It is still bioequivalent to immediate-release oxycodone,” Howe said. “If it's manipulated to be rendered into a viscous material … it can't be inhaled and it can't be injected or smoked effectively, so you can't get the euphoria that you would typically get.”
Creating an abuse-deterrent opioid has been an ongoing goal for drugmakers. Pfizer won approval in 2016 for its abuse-deterrent opioid called Troxyca ER, an extended release oxycodone hydrochloride and naltrexone hydrochloride pill for severe pain, but the drug still had some potential for abuse.
And the market for opioids has also tightened. Between 2011 and 2022, opioid prescriptions plummeted by nearly 45% — leaving some pain patients in the lurch.
Ongoing government actions against pharmacies could also compound the challenges for chronic pain patients.
The Department of Justice launched a lawsuit against Walgreens earlier this month for dispensing “dangerous opioids and other drugs” since 2012. The lawsuit puts more scrutiny on prescriptions for those who may need the drugs.
“The most recent Walgreens lawsuit with the DOJ has created a challenge for patients [who] really need treatment [and] really need the support,” Howe said. “They have trouble getting their medications. They're looked at, unfortunately, in a negative light if they have chronic pain.”
Roxybond was previously OK’d at other dosages — 5 mg, 15 mg and 30 mg — but the recent 10 mg immediate-release approval is an important level for many patients, offering another dosage that improves precision in safer pain management. And Howe hopes the formulation will help ensure pain patients can get the relief they need.
“Our focus is not to grow the market, but to make it safer,” Howe said.
