Two doses of Antibe Therapeutics’ chronic pain drug beat placebo at reducing osteoarthritis pain, boosting its case as an alternative to nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used to treat osteoarthritis as well as other ailments that cause chronic pain.
The Toronto-based biotech tested three doses of the drug—150 mg, 200 mg and 250 mg—against placebo in 385 patients with osteoarthritis of the knee. After two weeks of treatment, the two higher doses beat placebo at curbing pain, meeting the study’s primary endpoint.
The lowest dose arm wasn’t designed to measure a statistically significant difference from placebo, only to see whether it had any effect at all, but it did better than expected. The company is planning a phase 2/3 study that will look for the drug’s lowest effective dose and to serve as a registrational trial for FDA approval.
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“The success of this study is a worthy complement to the GI safety results already in hand. With the extensive learning that these Phase 2 studies have provided, we have a clear path forward including an opportunity to lower the dose further,” Antibe CEO Dan Legault said in a statement. “Through an adaptive registration trial we can maintain our clinical and commercial timelines, and focus on large market partnering.”
Antibe is developing the drug, ATB-346, as an alternative to NSAIDs like ibuprofen and naproxen, which are commonly used to treat osteoarthritis but are also linked to side effects such as ulceration and bleeding in the gut. ATB-346 is a derivative of naproxen that releases hydrogen sulfide, which—the hope is—boosts mucosal defense in the gastrointestinal tract to ward off those side effects.
Although the phase 2 trial involved patients with osteoarthritis, ATB-346 could be useful for other conditions treated with NSAIDs including rheumatoid arthritis, gout and ankylosing spondylitis.
The study reported side effects that typically accompany NSAID use, such as indigestion, acid reflux and dizziness, across all three treatment groups as well as in the placebo group. Of the 318 patients who received ATB-346, only one had elevated liver enzyme levels that were “clinically significant” during treatment. Ten days after treatment, around 10% of patients in each treatment group had elevated liver enzymes, but Antibe chalked that up to the concurrent use of acetaminophen.
“It is standard for pain trials to allow the use of other medications, commonly acetaminophen,” the company said in the statement. “Acetaminophen use, especially in the post-treatment assessment period, pre-existing liver conditions and concomitant statin use were associated with a majority of the LTE [liver transaminase elevation] incidents.”
“The LTEs will need to be considered moving forward, but are manageable from a clinical perspective. Given the robust upper portion of the dose-response curve, we anticipate lower doses will be effective and further optimize the safety profile of ATB-346,” said Antibe's chief medical officer, Joe Stauffer, in the statement.