Is the United States ready for a new type of opioid?

For people whose trust in the pharmaceutical industry has been damaged by the opioid crisis, hearing that a company is developing a new anesthetic claiming high pain-relief efficacy and lower dependence risk may raise alarm bells.

That is why Tris Pharma—a private, commercial-stage biopharmaceutical company—believes rebuilding trust is a key part of its launch strategy for cebranopadol, its new pain treatment.

"That will be the biggest challenge we face," said Ketan Mehta, Founder and CEO of Tris Pharma. "I think, especially in the pain management space, trust has been broken, and understandably so."

In December, Tris announced positive top-line data from its oral human abuse potential study, which suggested that cebranopadol has lower abuse potential compared with tramadol and oxycodone. The U.S. Food and Drug Administration has granted cebranopadol Fast Track designation.

Although cebranopadol acts on the mu-opioid receptor, Tris Pharma does not call it a traditional opioid. Not only because the term carries negative connotations, but Mehta also says cebranopadol is "a new class of analgesic" that does more than just act on opioid receptors.

In fact, cebranopadol is a dual nociceptin/orphanin FQ peptide (NOP) receptor and mu-opioid peptide (MOP) receptor agonist. Because it targets both NOP and MOP receptors, the drug is being evaluated in clinical trials to determine whether it can produce analgesic effects similar to traditional opioids while significantly reducing side effects such as euphoria, respiratory depression, and physical dependence.

In fact, according to research published in the journal Molecules, "NOP agonists, including cebranopadol, could be used to treat substance use disorders."

"You get the best of both worlds," Mehta said. "I think this is the transformative data we will show the FDA."

Why now?

Launching a new pain drug that targets opioid receptors may seem poorly timed. Although the national opioid prescribing rate fell to a 15-year low in 2020, according to the U.S. Centers for Disease Control and Prevention, opioid overdose death rates have not slowed.

In fact, data from the National Institutes of Health show that overdose deaths involving opioids surged from 21,089 in 2010 to 47,600 in 2017, then spiked to 80,411 in 2021.

In recent years, opioid overdose deaths have shifted dramatically from prescription narcotics to street drugs, including fentanyl, but the pharmaceutical industry's role in the crisis still hangs over the entire sector and continues to play out in courtrooms across the country. Recently, a federal appeals court in New York allowed the bankruptcy settlement of Purdue Pharma, the company that sold OxyContin, which will protect its owners, the Sackler family, from future lawsuits. Although Purdue has agreed to pay billions of dollars to victims, survivors, and states for its role in the opioid crisis, millions of Americans remain deeply addicted to opioids.

"It humbles me toward those who were taken advantage of by the industry, and it makes us realize the loss of trust," Mehta said. "Unfortunately, it makes everyone look bad."

So why is Tris trying to enter the market now?

"Opioid prescribing trends are continuing to decline, but the need to treat pain remains strong," Mehta said.

Mehta specifically pointed to the aging population—in just seven years, all baby boomers will be at least 65—and said there are about 50 million chronic pain patients in the United States.

"Older painkillers like NSAIDs... and other drugs, they are just not enough," he said.

"Opioid prescribing trends are continuing to decline, but the need to treat pain remains strong."

— Ketan Mehta, Founder and CEO of Tris Pharma

Despite this need, "there is really no one investing in the pain space right now," Mehta said. "If you look at the pipelines of big pharma, no one is investing. And that is where I think... small or mid-sized companies like ours have an opportunity to truly fill that gap."

A combination of experience and a spirit of risk-taking

Mehta came to the United States from India more than thirty years ago to pursue a master's degree in pharmaceutical sciences, and he has stayed ever since. He found a sense of belonging here, a natural fit.

"I just love this country. Its openness, it allows you to ask questions," he said. "No one discourages you from asking questions."

He says he has always been a curious "troublemaker," always asking "why," which suited his career in the pharmaceutical industry. Although he held research and marketing roles at various companies throughout his career and founded Tris in 2000, Mehta's first job after graduation was in the pharmaceutical division of Eastman Kodak.

Since then, the company has undergone many evolutions and no longer exists in the form it took when Mehta worked there. Despite inventing the first digital camera, it failed to keep pace in the transition from film to digital photography and was ultimately left behind by the times. Today, Mehta keeps a bronze camera on his office bookshelf as a reminder and a lesson.

"It tells me I have to innovate," he said. "Otherwise, the world can be very cruel, and you can be eliminated very quickly."

Mehta says that innovating in pharmaceuticals means taking calculated risks and focusing on patients, and Tris is already doing that. For example, its LiquiXR drug delivery technology has led to the development of several first-of-their-kind products in the ADHD space.

Now, although Tris has other products in its pipeline, including candidates for adult and pediatric ADHD, narcolepsy, and spasticity, Mehta says that as cebranopadol moves into Phase 3 clinical trials later this year, he has "bet almost the whole company" on this drug.

The company still has a lot of work to do to rebuild and earn the trust of regulators and prescribers, but Mehta says he plans to let the data speak and maintain "a level of transparency that people are not used to."

Tris is even conducting an additional respiratory depression study that goes beyond what is required for approval, trying to create "hardcore data" to demonstrate the drug's true potential.

"We have to report the data first, and then make claims," Mehta said. "You have to be very open and transparent, and let the experts make their own decisions, rather than telling them what to think."