Clene claims its PhII MS trial, half its intended size, cleared the primary goal. But can the biotech afford PhIII?
Clene Nanomedicine said its gold nanocrystal-based drug candidate, which failed an ALS trial last year, was better than placebo in a mid-stage study of patients with multiple sclerosis. But there are some big caveats to flag here.
The Phase II VISIONARY-MS study enrolled less than half (73 of 150) of the planned patient population, which the biotech has previously attributed to Covid-19. The trial was conducted in Australia, a point mentioned during an investor call when noting the study was mainly white (95% of patients). And it failed in the intent-to-treat group, only passing muster on the primary endpoint after excluding a group of patients.
The Salt Lake City biotech ended up conducting the primary analysis in a modified intent-to-treat population (mITT), which entailed excluding data from a 9-patient site with “LCLA testing execution errors” and excluding 25-foot walk data from another patient with a “change in mobility assist device.”
LCLA, or low-contrast letter acuity, was the primary endpoint of the study, which was met when viewing the mITT population but not achieved when analyzing the ITT, the biotech said Monday morning. Results for the ITT group were “directionally consistent with the mITT results” but didn’t clear the statistically significant hurdle.
Robert GlanzmanWith the primary outcome results, the company is already planning a late-stage trial, CMO Robert Glanzman said on the investor call. Dose data haven’t been fully analyzed yet, he noted.
Shares $CLNN slid more than 8% before the opening bell Monday. And the stock had fallen 54% over the past year, when it closed on Friday.
For the company to get into a Phase III, the biotech will likely need to raise more capital. In the investor presentation, Clene said it had “sufficient cash to hit key milestones in 2022.” The company had $26.3 million as of June 30, which is enough to carry it into next year. Despite a bear market, multiple biotechs have gone to the market within minutes or hours of dropping positive clinical data, hoping trial wins equate to fast cash.
The study tested CNM-Au8 in patients with stable relapsing remitting multiple sclerosis over a 48-week period at 11 trial sites. Patients received 15 mg, 30 mg or placebo daily as an adjunctive therapy to disease modifying therapies currently available.
On the main goal of LCLA letter change in the clinically affected eye, the p-value was 0.056. The pre-specified statistical threshold was set at a p-value of 0.10.
The drug also met the secondary endpoint of the modified Multiple Sclerosis Functional Composite (mMSFC) — which observed vision, walking, cognition and other measures — with a p-value of 0.0138. CNM-Au8 did not pass the secondary endpoint of time to repeated clinical improvement.
Asked about dosing on the investor call, Glanzman said dosing needs to be “explored in future studies more fully” but that “it’s very possible that even a lower dose could be effective over the long term.”
“It’s important to remember that MS is a chronic disease and we will fully expect that a patient will be taking CNM-Au8 for a lifetime and it will take more study to understand the time course,” Glanzman said.
Clene observed no treatment-related serious adverse events. Treatment emergent adverse events were “predominantly mild-to-moderate and transient,” the biotech said. One subject on the study drug and one on placebo dropped out of the study due to TEAEs.
The mean age of patients was 38.7 years. The mean time from diagnosis was 5.5 years and 49 months since relapse. Of the 73 patients, 51 were women.
In the potential Phase III study, Clene would expect to test the drug on top of standard of care and will look to use the mMSFC as a primary endpoint, executives said on the investor call. That would be a novel primary endpoint, and the company said it has yet to review the endpoint with the FDA.
The drug previously failed a mid-stage test in patients with ALS, but the biotech followed up that Phase II flop with open-label survival data showing the drug decreased risk of death.
Clene continued with its ALS program by including CNM-Au8 in a platform study with other investigational therapies from UCB, Biohaven, Prilenia Therapeutics and Seelos Therapeutics. Topline results from that study, the Harvard Mass General-run HEALEY ALS, will read out this quarter. Those data could support an NDA submission in the first half of next year, the biotech said.
Also this quarter, Clene expects to report topline data from a Phase II study of its drug CNM-ZnAg in Brazilian patients with acutely symptomatic Covid-19 who are not hospitalized.
