Amitriptyline Hydrochloride

iStock, ALLVISIONN AlgoTherapeutix blames a “strong placebo effect” for the mid-stage failure for its pain gel ATX01, but the company still believes in the promise of its candidate as Vertex Pharmaceuticals’ first-in-class drug Journavx opens up the non-opioid space. Just over a week after the landmark approval of Vertex Pharmaceuticals’ non-opioid pain drug Journavx, AlgoTherapeutix has suffered a setback in the space, with its investigational topical analgesic therapy ATX01 failing to significantly ease pain in patients suffering from chemotherapy-induced peripheral neuropathy. The Paris-based biotech said Tuesday that ATX01 showed “encouraging” efficacy signals, especially when given at the higher, 15% concentration dose. However, several study sites documented what CEO Stéphane Thiroloix in a statement called a “strong placebo effect,” which in turn prevented ATX01’s benefit from hitting statistical significance. Posthoc analyses of the study’s data showed that in trial centers with low placebo effect, 15% ATX01 elicited significantly better pain relief than placebo. Despite the lack of a significant response, Thiroloix called Tuesday’s readout “a significant step forward” for ATX01, pointing to promising signals of efficacy, such as the 1.6-point pain improvement, as measured by the Numerical Pain Rating Scale. ATX01 was also superior to placebo in terms of key secondary endpoints in posthoc analyses. Designed to be applied topically, ATX01 is a proprietary formulation of amitriptyline , an antidepressant that has been approved by the FDA in a tablet form to treat depression. AlgoTx’s version, however, leverages the non-systemic application of amitriptyline, which potentially dampens or blocks pain signaling locally, focusing on nerve fibers in the skin. Though it did not specifically spell out its future plans for ATX01, AlgoTx in its news release on Tuesday seemed to still believe in the promise of its candidate in chemotherapy-induced peripheral neuropathy. The company “sees a strong rationale to further explore the development of ATX01 15%,” AlgoTx noted, adding that it can look at other trial designs to minimize or even eliminate the placebo effect, such as enrichment/withdrawal strategies or a placebo run-in period. “There is the potential to design a new study, with additional mitigation strategies in place, to evaluate ATX01’s efficacy . . . without ambiguity,” Thiroloix said. BioSpace has reached out to AlgoTx for more clarity on ATX01’s path forward and will update this story accordingly. AlgoTx was previously testing ATX01 for erythromelalgia—a rare vascular condition that affects the extremities and causes intense pain—but according to the biotech’s website , a readout last year returned underwhelming data, forcing the biotech to discontinue the asset’s development in this indication. AlgoTx is also running early studies for ATX01 in painful diabetic peripheral neuropathy, COVID-induced neuropathy and phantom limb pain. AlgoTx’s mid-stage stumble on Tuesday comes after Vertex earlier this month won the FDA’s approval for Journavx, an inhibitor of the NaV1.8 voltage-gated sodium channel that marks the first new mechanism for analgesia in over 20 years—and potentially offering the U.S. a way out of its opioid crisis. According to data from the National Institute on Drug Abuse, nearly 74,000 people died from an overdose of synthetic opioids in 2022. Meanwhile, the Centers for Disease Control and Prevention estimated that the cost of opioid use disorder and related fatalities reached over $1 trillion in 2017. And Journavx may be only the beginning for this new class of pain medicines as several other biotechs seek to follow in Vertex’s footsteps. Lexicon, Algiax, Xgene and Tris Pharma are among those with non-opioid candidates in mid- to late-stage trials, for example. Meanwhile, newcomer Latigo Bio, which launched in February 2024 with $135 million in starting funds to advance its own oral NaV1.8 blocker LTG-001 and is now launching a Phase II trial , said in Friday SEC filing stated that it is now targeting up to $150 million in new funding.

MONDAY, Feb. 10, 2025 -- In a clinical guideline issued by the American College of Physicians and published online Feb. 4 in the Annals of Internal Medicine , recommendations are presented regarding the use of pharmacologic treatments for the prevention of episodic migraine headache in nonpregnant adults in outpatient settings. Amir Qaseem, M.D., Ph.D., from the American College of Physicians in Philadelphia, and colleagues examined the comparative effectiveness of medications that are beneficial for preventing episodic migraine to help clinicians select which medication to use. The guidelines include three recommendations. Monotherapy to prevent episodic migraine headache in nonpregnant adults in outpatient settings is suggested by choosing one of the following: beta-adrenergic blocker (metoprolol or propranolol), the antiseizure medication valproate, the serotonin and norepinephrine reuptake inhibitor venlafaxine, or the tricyclic antidepressant amitriptyline. To prevent episodic migraine headache in nonpregnant adults in outpatient settings who do not tolerate or inadequately respond to a trial or trials of one of these medications, monotherapy with a calcitonin gene-related peptide (CGRP) antagonist-gepant or a CGRP monoclonal antibody is suggested. Monotherapy with the antiseizure medication topiramate is suggested to prevent episodic migraine for those who do not respond to the suggestions in recommendations 1 and 2. An informed decision-making approach should be used, and benefits, harms, costs, patient values and preferences, contraindications, pregnancy and reproductive status in females, clinical comorbidities, and medication availability should be discussed when selecting pharmacologic treatment. "Adherence to pharmacologic treatment is crucial because improvement may occur gradually after initiation of a long-term treatment option for prevention of episodic migraine, with an effect that may become apparent after the first few weeks of treatment," the authors write. Clinical Guideline Evidence Review 1 (subscription or payment may be required) Evidence Review 2 (subscription or payment may be required) Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.