Clinical Catch-Up: August 16-20
It was another busy week in clinical trial news. Here’s a look.
COVID-19-Related
Histogen and Amerimmune Pharmaceuticals announced additional data from the Phase I trial of emricasan in mild symptomatic COVID-19 patients. Patients who completed treatment with the drug had a complete resolution of symptoms most commonly linked to mild COVID-19, such as a cough, headache, and fatigue at day 7. Emricasan is a potential first-in-class, oral pan-caspase inhibitor that is engineered to decrease the activity of enzymes that mediate inflammation and apoptosis (cell death).
Biophytis received a recommendation by the Data Monitoring Committee to continue patient recruitment into part 2 of the COVA study based on analysis of the safety data of the first 155 patients in the Phase II-III trial in COVID-19. Part 2 is a Phase III pivotal randomized trial of Sarconeos (BIO101) on the respiratory function of 310 or up to 564 COVID-19 patients, including 50 from Part 1. Sarconeos is an oral small molecule.
Pfizer and BioNTech submitted Phase I data to the FDA in support of the third booster shot of the vaccine. They also expect to submit the data to the European Medicines Agency (EMA) and regulators around the world in the new few weeks.
Claritas Pharmaceuticals initiated the Phase I trial of R-107 with CMAX in Adelaide, Australia. R-107 is a patented nitric oxide-released compound for treatment of COVID-19 and other viral infections.
Relief Therapeutics reported that NRx Pharmaceuticals, its U.S. collaboration partner, provided a safety update of Zyesami (aviptadil) which is in the NIH’s ACTIV-3 Critical Care Phase III study for severe COVID-19. No new safety concerns were observed and the trial’s review board recommended continuing enrollment.
AstraZeneca reported that its antibody cocktail, AZD7442, hit the primary endpoint in preventing COVID-19 in the PROVENT Phase III clinical trial. AZD7442 is a combination of two long-acting antibodies. In the study it decreased the risk of developing symptomatic COVID-19 by 77% compared to placebo. The combination is made up of tixagevimab and cilgavimab. Both antibodies were derived from B-cells donated by patients who had COVID-19 and recovered.
Non-COVID-19-Related
Rocket Pharmaceuticals announced the FDA had lifted the clinical hold it had placed on its Phase I trial of its RP-A501 for Danon Disease. RP-A501 is a gene therapy that includes a recombinant AAV9 capsid delivering a functional version of the human LAMP2B transgene. The clinical hold was placed to ensure the company modified the study protocol and revised guidelines for patient selection and safety management, not over safety concerns.
Axcella published results from its AXA1125-003 trial. Based on the positive findings, it initiated its EMMPACT Phase IIb trial of AXA1125 in biopsy-confirmed nonalcoholic steatohepatitis (NASH). The results evaluated AXA1125 and AXA1957 on safety, tolerability and effects on structures and functions of the liver. The data showed that both were well-tolerated, both demonstrated sustained reductions in key biomarkers of metabolism, inflammation and fibrosis over 16 weeks, but AXA1125 showed larger and more consistent reductions.
Brickell Biotech announced the final patient had completed the Phase III Cardigan II trial of sofpironium bromide gel, 15% in primary axillary (underarm) hyperhidrosis. It plans to announce topline data from the U.S. Phase III Cardigan I and II studies concurrently in the fourth quarter. Sofpironium bromide is a new chemical entity in the class of anticholinergics, which block the action of acetylcholine.
BioSight announced the initiation of a Phase II trial of its aspacytarabine for second-line treatment of relapsed or refractory myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The sponsored trial will be led by the Groupe Francophone des Myelodysplasies (GFM), the French Study Group of the European Myelodysplastic Syndromes (MDS) Cooperative Group (EMSCO). Aspacytrabine is a novel anti-metabolite, cytarabine covalently bound to asparagine, acting as a pro-drug of cytarabine.
Moderna is expected to launch a human clinical trial as early as this week for an mRNA-based vaccine against HIV. In a post to ClinicalTrials.gov, the company indicated it is looking for 56 people ages 18 to 50 who are HIV-negative. The trial is expected to launch on August 19 and end in the spring of 2023. The company is working with The University of Texas at San Antonio, George Washington University, Fred Hutchinson Cancer Research Center, and Emory University. It is a Phase I study. The company has two HIV vaccine candidates, mRNA-1644 and mRNA-1644v2-Core. Both were tested for safety before use on humans.
Istari Oncology initiated a Phase I/II sub-study of Pvsripo in head and neck cancer with or without checkpoint PD-1/L1 inhibitors. The expansion of the LUMINOS-103 trial is a Phase I/II basket trial that also includes studies in multiple tumor types. Pvsripo is a novel intratumoral viral immunotherapy that activates a patient’s innate and adaptive immune system to facilitate an anti-tumor immune response.
Cidara Therapeutics and Mundipharma AG completed recruitment of the Phase III ReSTORE trial of rezafungin as first-line treatment for candidemia and invasive candidiasis. Rezafungin is a novel once-weekly antifungal.
Orchestra BioMed published results from the MODERATO II trial of the BackBeat Cardiac Neuromodulation Therapy. This is a programmable and adjustable bioelectronic therapy used by way of an active implantable cardiac pulse generator. The device significantly decreased 24-hour ambulatory systolic blood pressure in patients with persistent hypertension.
Oxurion NV published positive Phase I data of THR-687 for the treatment of diabetic macular edema (DME). THR-687 is a highly potent integrin agonist. The drug was safe and well tolerated and demonstrated encouraging efficacy signals.
Novartis announced positive results from two Phase III trials of Beovu (brolucizumab) compared to aflibercept in DME. Year two of the KITE trial showed that a majority of patients who completed the initial 12-week cycle after the loading phase were maintained on a 12- and 16-week dosing interval through the end of the study.
Avadel Pharmaceuticals published data from its pivotal Phase III REST-ON trial of FT218 for excessive daytime sleepiness and cataplexy in adults with narcolepsy. FT218 is a once-nightly formulation of sodium oxybate that includes the company’s proprietary, drug delivery technology.
Praxis reported data from its PRAX-114 Phase IIa Part B proof-of-concept study for treatment of perimenopausal depression (PMD). It also included plans to advance PRAX-114 to a Phase IIb trial in women with menopausal and mood symptoms. In the Phase IIa study, patients showed improvements in menopausal and mood symptoms. PRAX-114 is an extrasynaptic GABAA receptor preferring positive allosteric modulator (PAM).
Galecto treated the first patient in its Phase IIa trial of GB2064 in myelofibrosis. GB2064 is an oral LOXL2 inhibitor.
AzurRx reported positive topline data from its Phase II Combination Trial of MS1819 in combination with current standard of care, porcine-derived pancreatic enzyme replacement therapy (PERT), for the treatments of severe exocrine pancreatic insufficiency in patients with cystic fibrosis (CF). The drug demonstrated clinically meaningful improvements in the primary efficacy endpoint, the Coefficient of Fat Absorption. MS1819 is a recombinant lipase enzyme derived from the Yarrowia lipolytica yeast lipase.
Abivax SA received approval for a Phase I trial of ABX464 in healthy Japanese volunteers by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). The study is required to include Japanese patients in its global Phase III program of the drug for ulcerative colitis. ABX464 is an oral therapy with a novel mechanism of action based on the upregulation of a single microRNA (miR-124) with potent anti-inflammatory effects.
NerveGen Pharma Corp. provided an update on its Phase I trial of NVG-291. They have completed the fourth of six planned dose cohorts in the single ascending dose portion of the study and recently received approval from the safety review committee to go ahead and initiate dosing in fifth cohort. NVG-291 modulates protein tyrosine phosphatase and is being developed for diseases that show injury to the nervous system, such as Alzheimer’s, traumatic brain injury and multiple sclerosis.
Adagene entered into a third clinical trial collaboration and supply agreement with Merck. They will run a dose escalation and expansion study of ADG106 with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) in advanced or metastatic solid and/or hematological malignancies. ADG106 is a fully human, ligand-blocking, agonistic anti-CD137 immunoglobulin G4 monoclonal antibody.
AbbVie published 12-week results from the Phase III ADVANCE study of atogepant for prevention of migraine in adults. The active treatment arm met the primary endpoint of statistically significant reduction in mean monthly migraine days across the 123-week treatment period. Atogepant is an oral CGRP receptor antagonist.
AstraZeneca’s Alexion halted its Phase III CHAMPION-ALS trial of Ultomiris (ravulizumab) for amyotrophic lateral sclerosis (ALS). The Independent Data Monitoring Committee recommended the halt after an interim analysis. Ultomiris is a long-acting C5 complement inhibitor approved for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). No new safety issues were reported.