“It's a wonderful morning for Lexicon, our scientists, clinicians and the patients and principal investigators,” summed up CEO and Director Lonnel Coats, as the biotech reported results from a phase 2 trial for its diabetic neuropathy therapy.
The results show that LX9211 improved average daily pain after six weeks compared to placebo in the low-dose group. But analysts were left unsatisfied with the top-line results, peppering executives with questions about pieces that were left out of the data drop during a Thursday morning conference call. They asked for a p-value, more information on dropout rates in the high-dose arm and specific rates of common side effects, which included dizziness and nausea, for each study group.
Executives didn’t bite, beyond previewing what they found in the top-line analysis, instead promising to package up the results for a future medical journal instead.
But Coats believes that the data previewed today are enough to confirm “impressive” preclinical data and translation into humans, and could be the impetus for larger companies to reach out about a possible partnership with Lexicon.
“The inbound interest has always been high on this asset. I think most have been waiting for whether there's going to be a translation of a signal in humans,” Coats said. “That signal has now been achieved.”
LX9211 was tested in patients with diabetic neuropathy, a type of nerve pain caused by high blood sugar that can occur in people with diabetes. The phase 2, proof-of-concept Relief-DPN-1 study, which featured 319 patients, was looking to see whether the therapy was able to improve pain compared to measures at the start of the trial. The study had a low- and high-dose arm, plus a placebo group, and was conducted at 40 sites across the U.S.
While the low-dose arm showed a significant reduction in pain, Lexicon said patients in the high-dose arm plateaued. Both treatment arms saw a separation from placebo after the first week. The effect was consistent regardless of age, sex, concurrent use of other medications and baseline pain score when the trial began, the company said.
As for safety, Lexicon saw a higher incidence of adverse events in the treatment arm, particularly in the high dose group, but no serious events were reported. The higher incidence of adverse events was “consistent with our expectations” for the patient group, according to Chief Medical Officer Craig Granowitz, M.D., Ph.D.
That’s because the higher, 200 mg dose was “at the very limit of tolerability based on underlying data.” The high-dose group had more dropouts compared to low-dose patients, which Granowitz said could suggest why the average daily pain score was lower in this group.
“We believe that based on the [pharmacokinetics] that we showed today, and our understanding of this drug that we have a lot of opportunity to maximize the benefit-risk ratio of this drug,” Granowitz said.
Granowitz also explained that the common side effects—dizziness, headache and nausea—are a result of LX9211 blocking the same neuronal pathway that is associated with the type of nerve pain that occurs with diabetic neuropathy. That’s why the result was not a surprise.
“The good news is that we have a lot of dials that we can modulate to further optimize the dosing and hopefully magnify the benefit versus the side effect trade-off over time,” Granowitz said. “And that really is the area that we are most interested and focused on [for] some of the upcoming studies.”
So what’s next for LX9211? There is, of course, the planned publication of more robust data at an upcoming medical conference and in a peer-reviewed journal, which may answer more of the analysts’ questions. But Coats said the asset is also poised for partnerships, with this midphase data now in hand.
“When we look down the road, it's our objective certainly to partner this compound because it is not our intent to build a commercial organization that goes into primary care, where you have broad indication, broad opportunities that will be better suited in the hands of a partner,” the chief executive said.
Lexicon is also not interested in pursuing commercialization outside of the U.S., which means a partnership is the best bet.
“Our strategy is very simple. We've now shown proof of concept. I think the evidence here is clear—it is not ambiguous, it is very clear,” Coats said. “I fully expect we'll be in dialogue about advances in some kind of partnership in the very near future.”
Lexicon will also move LX9211 into late-stage development, although executives were mum on what that study would entail.
The therapy, which was licensed from Bristol Myers Squibb in 2016, holds a fast-track designation from the FDA.