How Purdue’s $272M addiction payout funded a new home for its discarded non-opioid research

Don Kyle spent more than 20 years working for Purdue Pharma, right through the US opioid epidemic that led to the company’s rise and eventual infamy. But contrary to Purdue’s focus on OxyContin, Kyle was researching non-opioid painkillers — that is, until the company shelved his research.

As the company’s legal troubles mounted, Kyle found an unlikely way to reboot the project. In 2019, he took his work to an Oklahoma State University center that’s slated to receive more than two-thirds of the state’s $272 million settlement with Purdue over claims that the drugmaker’s behavior ignited the epidemic of opioid use and abuse.

More than three years after the university agreed to take on the work, the project is finally underway, led by Kyle as the new CEO of the university’s National Center for Wellness & Recovery, and flush with Purdue settlement cash. It comes as the US sees more than 80,000 opioid overdose deaths a year, a figure that has steadily climbed since 2015.

“When I sit down and try to explain the circumstances of what brought me here, it makes my head spin,” Kyle said in an interview.

Much of the estimated $50 billion in opioid settlements from drugmakers, distributors and pharmacies has yet to be spent, and limited public data indicate the first allocations have largely gone toward mental health programs and addiction treatment. Less visible is that drug researchers and digital health companies are vying for and sometimes winning a portion of those dollars.

“It’s something that hasn’t been talked about much,” said Christine Minhee, founder of OpioidSettlementTracker.com.

Opioids are powerful and effective. And while they’re addictive, they’re also cheap and accessible, which has limited the incentives to develop pain treatment alternatives that would almost certainly be more costly for insurers and legitimate patients.

Venture capital investment in companies working on opioid alternatives totaled $89 million in 2022, a five-year low, according to public data compiled by DealForma CEO Chris Dokomajilar. The NIH’s Helping to End Addiction Long-term Initiative includes $99.5 million for translational research into novel pain drugs, but those grants typically aren’t enough to cover research and clinical development costs over a lengthy time period.

“Usually, faculty researchers have to write grants every year to try to sustain funding. But we have a longer funding road ahead of us,” Kyle said of the Purdue settlement.

At one point, Kyle oversaw a Purdue division with more than 100 employees. Asked why Purdue mothballed his team’s research, a company spokeswoman forwarded a statement: “While Purdue has actively continued work on potential treatments for pain and addiction, we could not pursue work on every possible path, and made a decision at the time to direct resources elsewhere.”

An awkward question

In 2019, Kyle sent a blind email to Oklahoma State officials imploring them to restart his work after the university’s National Center for Wellness & Recovery got $197.5 million from the Purdue settlement. The center’s goal was to become a magnet for addiction treatment and non-opioid drug development.

At the time, Kyle was still a vice president at Purdue, raising an awkward question: Why would the university work with a researcher from the company that aggressively marketed OxyContin and is widely considered to have planted the seeds of the epidemic?

“His work as a chemist is world class, and his vision matched with ours in how we might work together to develop nonopioid, nonaddictive approaches to treating pain,” said Johnny Stephens, president of the university’s Center for Health Sciences, in a statement.

Another major selling point was that, upon Kyle’s urging, Purdue granted the university a free license to 20,000 experimental molecules from Kyle’s old lab. Discoveries — and profits — based on the molecules would belong to the university and any research partners, according to Oklahoma State.

In a statement, Purdue said it provided the molecules and other materials “to support research with the potential to advance public health.” It doesn’t get a profit stake in any successful work that comes out of the effort.

Kyle went from pitching the university to, in 2022, becoming the CEO of its National Center for Wellness & Recovery. In the next two years, the center plans to put some of its compounds in clinical trials, including those that are designed to stimulate the brain’s opioid receptors but without the side effects and risks of existing opioids.

Another goal, through a partnership with the University of Arizona, is developing better medications than what’s currently on the market for fentanyl overdoses.

For Kyle, it would be a second chance.

“When all of the acid rain of the opioid crisis started falling down on Purdue and these other parts of the organization, it conflicted with the pride I had,” Kyle said. “And then all these assets went on the shelf, which was a heartbreaker.”

Drugs that alleviate pain without triggering addiction represent something of a holy grail in drug development. Often, pain compounds show promise in animal studies but fail to translate to humans, or cause unforeseen side effects.

Centrexion, led by former Pfizer CEO Jeff Kindler, saw its knee pain drug CNTX-4975 miss its main goal in Phase III clinical trials last year.

Around the same time, Acadia Pharmaceuticals didn’t hit its primary goal in a Phase II post-operative study of its drug ACP-044 that’s supposed to tamp down reactive chemicals that cause tissue injury and inflammation.  Next up is Vertex’s experimental pill VX-548, which is undergoing a Phase III clinical trial after it significantly reduced patients’ pain compared to placebo in two post-operative trials.

Kyle is well familiar with the struggle faced by those trying to find alternatives. At Purdue, several of his division’s non-opioid compounds didn’t reach statistical significance in clinical trials.

“There’s a lot of unknowns when you get into a human trial,” Kyle said.

An app for opioid use disorder

Opioid settlements are also funding another newer technology: digital health — or rather, getting government payers and insurers to cover these products.

North Carolina earmarked $1.85 million in opioid abatement funds to pilot Pear Therapeutics’ addiction software in Medicaid recipients. The company’s app — which the FDA cleared for opioid use disorder — delivers cognitive behavioral therapy to change persistent negative thoughts that fuel addiction.

The company declined to disclose how much total money Pear has received from opioid settlements. Each state has its own approach for distributing funds, and of the money allocated so far, limited and scattered public data exist on which specific entities are receiving resources.

The largest opioid settlement — $26 billion that will be paid by Johnson & Johnson, AmerisourceBergen, Cardinal Health and McKesson — says states should spend at least 70% of their settlement money on future opioid abatement, a category that states are interpreting to include digital health platforms.

GATC Health, a California company, is petitioning for settlement money to move the company’s work beyond the preclinical stage. It says it has used its artificial intelligence platform to identify drug compounds that aim to rewire faulty brain wiring that drives addiction, with the goal of improving upon existing addiction treatments like buprenorphine and methadone.

“We believe the drug that we’ve invented for opioid addiction and specifically fentanyl addiction is very novel. So we’ve been sharing that preliminary information with a number of groups, federal, state and local agencies,” said Tyrone Lam, GATC’s chief operating officer.

Meanwhile, Kyle said Oklahoma State cannot count on Purdue settlement dollars to pay the bills forever. But it can help push the programs forward, and if they’re successful, let the center pull in cash from additional sources, such as licensing deals with drugmakers or even starting their own companies.

While at Purdue, Kyle’s division surveyed 100 years of opioid research literature for drug discovery leads. Once again, he’s returning to the past, as the university center adds lab space and builds out its chemistry team to advance his body of work.

“It’s a twist of fate,” Kyle said.

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