– ATB-346 demonstrates superiority to placebo in reducing osteoarthritis pain –
– ATB-346 is more potent than expected; lowest effective dose still to be established –
– Antibe plans pivotal Phase 2/3 adaptive registration trial –
Antibe Therapeutics Inc. (TSXV: ATE, OTCQB: ATBPF) is pleased to announce that its lead drug, ATB-346, met the primary endpoint in the Phase 2B dose-ranging, efficacy study. Both the 250 mg and 200 mg doses of ATB-346 demonstrated superiority to placebo in reducing osteoarthritis (“OA”) pain with a high level of statistical significance. The 150 mg dose of ATB-346, although not powered for statistical significance, demonstrated more potency than expected and the lowest effective dose is still to be established. The drug was safe and well tolerated during this study. The Company is planning a pivotal Phase 2/3 randomized, controlled trial with an adaptive design that will define the lower end of the dose-response curve.
“We are pleased that our drug provided excellent pain relief to the patients in the study,” remarked Dan Legault, Antibe’s CEO. “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. Through an adaptive registration trial we can maintain our clinical and commercial timelines, and focus on large market partnering.”
A total of 385 patients with osteoarthritis (OA) of the knee were randomized to either placebo or ATB-346 administered once daily: 250 mg, 200 mg or 150 mg. The primary endpoint in the study was the change from baseline in the WOMAC pain subscale score as measured at the end of the 14-day treatment period. The 250 mg and 200 mg doses were powered for statistical significance and the 150 mg dose was powered to only observe an efficacy response.
ATB-346 demonstrated superiority to placebo at doses of 250 mg (p-value of 0.01) and 200 mg (p-value of 0.007). Similar efficacy was observed between these doses, suggesting that the upper range of the dose-response curve has been reached. The 150 mg dose demonstrated a robust efficacy response and had it been equivalently powered to the other treatment arms, the Company believes it would have achieved statistical significance. As such, the lower portion of the dose-response curve remains to be established.
In addition, both the 250 mg and 200 mg doses of ATB-346 demonstrated a highly statistically significant reduction in the WOMAC stiffness subscale score (p-value < 0.001 for both doses) and both doses were superior to placebo in the WOMAC difficulty performing daily activities (DPDA) subscale score (p-value of 0.004 and 0.001, respectively). While not statistically powered, the 150 mg dose of ATB-346 nonetheless demonstrated a statistically significant improvement in stiffness compared to placebo (p-value of 0.03) and displayed an efficacy response in DPDA.
Adverse events typically associated with NSAID use, such as dyspepsia, acid reflux and dizziness, were comparable across placebo and all three treatment arms of ATB-346. There were very few serious adverse events or events leading to withdrawal of treatment. Only 1 out of 318 patients administered ATB-346 had clinically significant, temporary liver transaminase elevations (LTEs) during the 14-day treatment period. At the post-treatment assessment (day 24), patients in the 250 mg, 200 mg and 150 mg treatment arms had clinically significant, temporary LTE incidences of 12.1%, 8.0% and 8.2%, respectively. It is standard for pain trials to allow the use of other medications, commonly acetaminophen. 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 incidents. Accounting for these factors yields clinically significant, temporary LTE incidence rates of 4.5%, 3.2% and 3.3%, respectively, suggesting a liver safety profile for ATB-346 comparable to commonly prescribed NSAIDs and well below that observed with acetaminophen (39% clinically significant LTE incidence rate; National Institutes of Health).
Joe Stauffer, Antibe’s Chief Medical Officer, commented, “I joined Antibe to help set a new standard of safety and effectiveness in the treatment of pain and inflammation. The results of this study, in conjunction with the profound GI safety results already demonstrated, indicate that we are on track to this new standard in patient care. 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.”
To establish the lowest effective dose of ATB-346, the Company is planning a pivotal Phase 2/3 randomized, controlled trial with an adaptive design. Antibe anticipates that this efficacy trial will compare multiple doses of ATB-346 to placebo in OA patients over a 12-week period. It is the Company’s intention to submit this study to the U.S. FDA as a formal registration trial.
The clinical study was conducted by Veristat, LLC in 39 clinical sites across Canada. David Vaughan, Antibe’s Chief Development Officer, commented, “We would like to express our gratitude to the Veristat team and the clinicians across the country for their commitment and contribution to this well-run and successful clinical trial.”
ATB-346 is a hydrogen sulfide-releasing derivative of naproxen. Nonsteroidal anti-inflammatory drugs (“NSAIDs”) are the most commonly used therapy for osteoarthritis, but their use is associated with a high incidence of gastrointestinal ulceration and bleeding. NSAIDs are also widely used in conditions such as rheumatoid arthritis, ankylosing spondylitis, gout, and general pain reduction, with a similarly high rate of gastrointestinal ulceration and bleeding. It is well-accepted that patients with these conditions would benefit greatly from an effective, non-addictive, GI-sparing anti-inflammatory/analgesic agent such as ATB-346.
About Antibe Therapeutics Inc.
Antibe develops safer, non-addictive medicines for pain and inflammation. Antibe’s technology involves the linking of a hydrogen sulfide-releasing molecule to an existing drug to produce an improved medicine. Antibe’s lead drug, ATB-346, targets the global need for a safer, non-addictive drug for chronic pain and inflammation. ATB-352, the second drug in Antibe’s pipeline, targets the urgent global need for a non-addictive analgesic for treating post-surgical pain, while ATB-340 is a GI-safe derivative of aspirin. Citagenix Inc., an Antibe subsidiary, is a market leader and worldwide distributor of regenerative medicine products for the dental marketplace. www.antibethera.com.
Forward Looking Information
This news release includes certain forward-looking statements, which may include, but are not limited to, the proposed licensing and development of drugs and medical devices. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking, including those identified by the expressions “will”, “anticipate”, “believe”, “plan”, “estimate”, “expect”, “intend”, “propose” and similar wording. Forward-looking statements involve known and unknown risks and uncertainties that could cause actual results, performance, or achievements to differ materially from those expressed or implied in this news release. Factors that could cause actual results to differ materially from those anticipated in this news release include, but are not limited to, the Company’s inability to secure additional financing and licensing arrangements on reasonable terms, or at all, its inability to execute its business strategy and successfully compete in the market, and risks associated with drug and medical device development generally. Antibe Therapeutics assumes no obligation to update the forward-looking statements or to update the reasons why actual results could differ from those reflected in the forward-looking statements except as required by applicable law.
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