A pair of new drugs developed locally fell flat in recent clinical trials, dealing a blow to Chicago’s fledgling biotech industry and one of its scientific stars.
In late January, Aptinyx’s treatment for diabetes-related pain failed a U.S. Food & Drug Administration Phase 2 study. This month, a depression drug developed by Aptinyx predecessor Naurex, which was acquired in 2015 by Irish drugmaker Allergan for $1.7 billion, flunked three Phase 3 studies.
The test results suggest neither remedy will reach the vast markets backers targeted—millions of people suffering from common chronic conditions. Now Evanston-based Aptinyx will seek approval of narrower applications for NYX-2925 with less potential upside. Shares of the newly public company have plunged 77 percent as investors adjusted their expectations. As for Allergan, it’s unclear whether it will continue to pursue rapastinel, the Naurex drug. Another casualty is Northwestern University researcher Joe Moskal, whose work led to the creation of both startups. He says in an email that he was “disappointed and surprised” by the rapastinel results, but insists there’s “ample evidence that it can help patients who desperately need better, safer therapeutic options for treating depression and other (central nervous system) disorders.”
Moskal is chief scientific officer of Aptinyx, as well as a major shareholder. The 390,146 Aptinyx shares he held as of the most recent SEC disclosure, in June, have lost more than $5 million in value since the bad news came out Jan. 16.
“These recent study results just exemplify how difficult it is to develop novel drugs in this space,” Moskal says of the disappointing Aptinyx and Allergan trials. Still, he maintains the failed drugs have shown “efficacy in patients suffering difficult disorders.”
A subset of patients with advanced painful diabetic peripheral neuropathy showed the greatest treatment benefit from NYX-2925, according to data Aptinyx presented at the Cowen & Company Health Care Conference on March 13. Among those patients, the 50-milligram dose proved “clinically meaningful and statistically significant,” the report says.
With more than $100 million raised in a 2018 IPO, Aptinyx is “readily able to finance the next set of studies, to cover all of our needs without having to raise additional money,” CEO Norbert Riedel says. Aptinyx raised $102 million in the offering. Reidel says he has $150 million on his balance sheet.
‘SHOTS ON GOAL’
The next few months will be telling. In the first half of 2019, Aptinyx will release Phase 2a data on how NYX-2925 fared in patients with fibromyalgia, as well as Phase 1 data on a pipeline drug for the treatment of cognitive impairment related to Parkinson’s disease. Meanwhile, Phase 2a data on the ability of yet another pipeline drug, for post-traumatic stress disorder, is expected during the first half of next year.
“I’ve seen a lot of early-stage companies come and go. One of the things I liked about these guys is they have multiple shots on goal,” says Gary Nachman, a BMO Capital Markets analyst. “There’s no question the lead program missed in the first big study and that was a disappointment.” But the early fibromyalgia study results, including 11 patients, noted changes in the brain, which shows the compound works, he adds.
Despite differences between the oral Aptinyx drugs and intravenous Naurex drugs, the industry has been watching Allergan closely to gauge rapastinel’s possibilities as an adjunctive treatment of major depression.
Allergan didn’t respond to requests for comment. But in a March 6 statement announcing the Phase 3 findings, Chief Research and Development Officer David Nicholson said: “We are deeply disappointed with these results, and they are a vivid reminder that drug development is extremely challenging, especially in mental health. . . .We expect to make a decision on these programs during the course of 2019.”
Moskal’s work is unique in that it focuses on controlling pathways in the brain, called NMDA receptors, which shows promise in treating neurological disorders. One of the challenges with testing depression and pain drugs, experts say, is that placebos yield positive results in some patients, making it difficult to tell just how effective novel drugs really are.
The risk isn’t without reward. Informa Pharma Intelligence predicts the depression drug market will grow from $4.6 billion in 2015 to $7.3 billion in 2024, driven primarily by pipeline drugs from new therapeutic classes like NMDA medications. Another example is Johnson & Johnson’s esketamine, sold under the brand name Spravato. The drug costs $4,720 to $6,785 in the first month, and then declines to $2,360 to $3,540 monthly, the drugmaker recently told Bloomberg.
“Over the decades of my career, I have learned the most from the experiments that were not viewed as wildly successful,” Moskal says. “And while they can be tough in the moment, they have given me a much broader perspective and generally catalyzed my next successes. “