Allay Therapeutics, a clinical-stage biotechnology company pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation, today announced the first-ever clinical data showing non-opioid pain relief lasting two weeks after a single administration. Current post-surgical pain products have shown effectiveness for a maximum of three days after a single dose. The data come from a Phase 1b/2a clinical study of Allay’s first candidate, ATX-101, in development to treat pain after total knee arthroplasty (replacement), or TKA, surgery. TKA surgery is performed over one million times each year in the United States and is associated with a lengthy, painful recovery often managed with significant opioid usage. ATX-101 is a small dissolvable product candidate incorporating the validated local analgesic bupivacaine. It is designed to be incorporated into surgery to deliver continual, localized pain relief that matches the pain trajectory patients typically experience after TKA surgery.
Allay Therapeutics was formed with a singular goal: to allay patients’ fears of extended painful recoveries and reliance on opioids after surgery. Allay’s technology platform combines validated local analgesics and biopolymers in dissolvable candidates designed to deliver pain relief within a targeted site over days to weeks, or longer. Changes to the drug-biopolymer configuration and manufacturing process allow tuning of the amount of drug delivered and differing rates of release for each product candidate. This tunability permits a wide range of potential therapeutic profiles for different kinds of pain.
“Pain management innovation has stalled for too long in the face of the enormous need created by the opioid crisis and a growing number of patients undergoing painful surgeries where rapid recuperation is crucial for long-term outcomes. Allay was founded to deliver a gentler longer-term recovery for patients and ease the burden of pain management and opioid use for the healthcare system,” said Adam Gridley, chief executive officer of Allay Therapeutics. “We believe these unprecedented clinical data could be the start of a new era of ultra-sustained pain management. Our focus now is a Phase 2b trial of ATX-101 to enroll over 300 patients in the United States, as well as the advancing of our pipeline across several new areas of pain representing major unmet needs globally.”
Currently, approved post-surgical pain products using local anesthetics have demonstrated effectiveness for a maximum of three days. They are often challenging to administer consistently and have variable outcomes. They are insufficient to fully support recuperation, which often results in supplementary opioid use, readmissions, and extended recovery, all resulting in significant additional healthcare costs. Opioids are short-term medications which act systemically on the body and have a range of side effects – including respiratory depression, greater pain sensitivity, and the significant risk of abuse and addiction – which have fueled a major health crisis in the United States and beyond.
The recently completed Phase 1b/2a clinical study of ATX-101 was an open-label dose-ranging study at two Australian clinical sites which evaluated 22 patients undergoing TKA with ATX-101 implants incorporating approximately 250 mg, 750 mg, and 1,500 mg doses of bupivacaine, respectively, of which 15 patients received the 1,500 mg dosage. The study was designed to evaluate safety and pharmacokinetics of ATX-101 in adult subjects in primary unilateral TKA while also examining dose response, pain scores, opioid use, and overall impact on quality of life during recuperation. Originally planned to enroll up to 30 patients with up to 2,000 mg doses, the study was concluded early based on achieving compelling pain reduction and opioid use reduction data with only 1,500 mg.
The preliminary summary study outcomes include:
1. Over 14 days, the cohort treated with 1,500 mg of ATX-101 took between half to two-thirds less opioids than a typical TKA patient, and 80% were off opioids at the end of that period relative to approximately 50% for the standard of care, according to published literature.
2. In the same cohort, ATX-101 significantly outperformed the standard of care throughout the 14day period for both the duration and magnitude of effect, using proprietary data sets of pain scores from clinical trials after TKA surgery. In this study, ATX-101 kept patients’ post-surgical pain in the zero or mild range for at least 14 days, relative to the published standard of care that typically results in severe short-term pain followed by moderate pain lasting for weeks. The standard of care includes various repeatedly dosed medications, including opioids.
3. ATX-101 delivered highly predictable dose responses across all three cohorts. It showed a clear linear relationship through the 14-day period between dose and maximum systemic concentration, as well as between dose and pharmacokinetic area under the curve, which represents total exposure to drug (R2 > 0.98). Predictable dynamics of drug delivery are a necessary property for therapeutic products like ATX-101 to support confidence in dosing selection.
4. ATX-101 delivered meaningful continual dosing throughout the 14-day period studied. During the acute phase of 0-4 days, comparable levels of bupivacaine were delivered by ATX-101 as compared to competitor products in published TKA studies. According to published literature, all other approved approaches using bupivacaine in TKA are no longer detectable five days after administration, whereas ATX-101 showed meaningful systemic levels through 14 days.
5. ATX-101 was observed to be generally well-tolerated in the study and no serious adverse events related to the product were seen.
“These data suggest an exciting therapeutic profile very different from anything in the current surgical pain management toolkit. The standard of care struggles to adequately serve patients in settings like TKA, which typically involves significant short-term and longer-term pain across a lengthy recuperation period,” said David Dalury, M.D., Clinical Professor of Orthopedic Surgery at the University of Maryland School of Medicine and Chief of Orthopedics at the University of Maryland St. Joseph Medical Center. “In orthopedic surgery, we are looking for simple, non-opioid solutions with consistent outcomes beyond two to three days that help patients return to normal function faster, to support earlier discharges and reduced need for ongoing clinical management. ATX-101 has made a promising step towards these goals and I look forward to further clinical data.”
Beyond ATX-101, Allay has developed proof-of-concept of new implant variants, injectable formulations, formulations to permit patient self-dosing ‘on demand,’ and formulations that incorporate a variety of small molecules and other local analgesics.
Allay Therapeutics was founded in 2017 by The Foundry incubator and Lightstone Ventures’ Singapore fund. Following the acquisition of polymer innovator Orchid Medical in 2018, the company initiated pre-IND discussions with the FDA and in 2019 completed a $25 million Series B financing led by NEA, with additional participation by Lightstone Ventures and Brandon Capital Partners.
Allay intends to proceed into a Phase 2b study of ATX-101 in the United States in 2021 and pursue regulatory filings with the United States Food and Drug Administration to support the Phase 2b study and a future potential Phase 3 clinical study, with a targeted NDA submission in 2024.
About ATX-101: In development to treat pain following total knee replacement surgery
ATX-101 is a novel configuration of an approved, well-characterized, validated intracellular sodium ion channel blocker, bupivacaine, and a biopolymer that has been designed to provide weeks of pain relief following total knee arthroplasty (replacement), or TKA, a common orthopedic surgery. ATX-101 has a high density of drug within its small footprint to allow for ultra-sustained analgesia. It is placed at the end of standard surgery, in minutes, to deliver its analgesic effect over weeks before dissolving into water and carbon dioxide over a longer period.
Summary outcomes from a Phase 1b/2a clinical study of ATX-101 demonstrated sustained pain relief lasting at least two weeks, with significant outperformance of historical pain relief scores provided by other approaches following TKA. Across all clinical and preclinical studies, ATX-101 appears to be welltolerated with minimal systemic exposure, with no serious adverse events.
TKA recuperation is currently managed with short-term products that offer only up to two or three days of pain relief and are highly variable in impact, and as a result are often supplemented with opioids. These current treatments do not adequately support the patient’s early ‘breakthrough pain’ period or subsequent rehabilitation. Where local anesthetics are used, they can involve complex procedures that are difficult to administer consistently and to the precise site of pain. The United States alone currently sees over one million TKAs annually with an annual growth rate of 20%, creating a strong need for nonopioid solutions to facilitate outpatient procedures and longer-term recuperation.
About Allay Therapeutics
Allay Therapeutics is pioneering ultra-sustained analgesic products to transform post-surgical pain management and recuperation for patients and physicians. Our proprietary technology platform combines validated non-opioid analgesics and biopolymers to create dissolvable candidates to deliver pain relief within a targeted site over weeks: an order of magnitude greater than the longest-lasting pain treatments currently available. Our platform and vision were shaped by The Foundry incubator and Lightstone Venture’s Singapore Fund. Allay unites a dynamic, global team of entrepreneurs, scientists, clinicians and innovators in the San Francisco Bay Area and Singapore. Learn more at allaytx.com.
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Clinical trial data on file with company.