Clinical Catch-Up: Vertex, Ayala, Arrowhead, Dyne & More

Cancer Research

Each week in the biopharma industry, dozens of clinical trial announcements exist. BioSpace takes a representative look at some that could have a big impact on cancer, diabetes, presbyopia and Duchenne muscular dystrophy, among others.

Ayala Pharmaceuticals announced positive interim data from Part A of the ongoing Phase II/III pivotal RINGSIDE trial of AL102 in desmoid tumors. The drug is a potent, selective, oral gamma-secretase inhibitor, demonstrating substantial anti-tumor activity as a single agent measured by MRI. The safety data was also encouraging, suggesting the drug was well tolerated. One patient reached an unconfirmed partial response at week 16. Desmoid tumors, also called aggressive fibromatosis or desmoid-type fibromatosis, are connective tissue tumors. They don’t metastasize but often aggressively infiltrate neurovascular structures and vital organs.

Vertex Pharmaceuticals announced that the U.S. Food and Drug Administration has lifted the clinical hold placed on its Phase I/II trial of VX-800. The therapy is an investigational stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for type 1 diabetes patients with impaired hypoglycemic awareness and severe hypoglycemia.

So far, only three patients had been dosed in the Phase I/II trial, with two receiving half the target dose in Part A of the study and a third receiving the full target dose in Part B. VX-880 has the potential to restore the body’s ability to regulate glucose levels by restoring the function of pancreatic islet cells. The agency placed the clinical hold in May, claiming insufficient data to support dose escalation.

Arrowhead Pharmaceuticals dosed the first patients in two Phase I/IIa trials of ARO-MUC5AC and ARO-RAGE. These drugs are investigational RNA interference (RNAi) therapeutics designed to decrease the production of the mucin 5AC (MUC5AC) and the receptor of the advanced glycation end products (RAGE), respectively, as possible treatments for various muco-obstructive and inflammatory pulmonary diseases. AROMUC5AC-1001 is evaluating the drug in patients with moderate-to-severe asthma. ARORAGE-1001 is evaluating that drug also in mild-to-moderate asthma.

Dyne Therapeutics reported that the FDA had lifted the clinical hold on its clinical study of DYNE-251 in Duchenne muscular dystrophy (DMD) patients amenable to skipping exon 51. The company expects the Phase I/II trial to launch in mid-2022. The agency placed a hold on the company’s Investigational New Drug (IND) application in January and requested more clinical and non-clinical data for the therapy. The study will be global and is a multiple ascending dose (MAD) study with a long-term extension study. Dyne plans to enroll 30 to 50 ambulant and non-ambulant males with Duchenne ages four to 16 years whose dystrophin mutations are amenable to exon 51 skipping therapy.

Eyenovia announced that its strategic partner Arctic Vision (China), enrolled the first patient in its Phase III trial of ARVN003 (MicroLine) for presbyopia (far-sightedness). Arctic Vision obtained a license for the development of the therapy from Eyenovia in August 2020 for Greater China and South Korea. It also includes Eyenovia’s development-stage candidate for pediatric progressive myopia (nearsightedness), MicroPine. Earlier, Arctic Vision licensed Eyenovia’s development-stage candidate for pharmacological mydriasis (dilation of the pupil), MydCombi.

Veru published data in the New England Journal of Medicine Evidence demonstrating that its sabizabulin treatment significantly decreased deaths in high-risk hospitalized COVID-19 patients. The results were from a Phase III study of the drug, a novel dual antiviral and anti-inflammatory agent for the treatment of hospitalized moderate-severe COVID-19 patients at high risk for acute respiratory distress syndrome (ARDS) and death. Patients in both treatment groups received standard of care, including Gilead Sciences’ remdesivir, as well as dexamethasone, anti-IL6 receptor antibodies, and JAK inhibitors. It hit the primary endpoint of a statistically significant and clinically meaningful 55.2% reduction in deaths compared to placebo. It also hit key secondary endpoints with drops in days in ICU, days on mechanical ventilation, and days in the hospital.

Enlivex Therapeutics dosed the first patient in a Phase I/II trial of Allocetra combined with chemotherapy in patients with peritoneal metastases arising from solid cancer. It is expected to enroll about 12 patients across four cohorts. Two cohorts will be of intra-patient and intra-cohort dose escalation, followed by two additional cohorts comparing administration of Allocetra at the selected dose either before or after administration of SOC via a pressurized intraperitoneal aerosol chemotherapy procedure. Allocetra is a universal, off-the-shelf cell therapy designed to reprogram macrophages into their homeostatic state.

Radius Health randomized the first patient in its Phase II/III SCOUT-015 trial of RAD011 for hyperphagia and related neuro-behavioral symptoms in Prader-Willi Syndrome (PWS). PWS is a rare genetic disease marked by insatiable appetite (hyperphagia), which leads to obesity and type 2 diabetes, and includes mild to moderate intellectual impairment and behavioral problems. RAD011 is a synthetic cannabidiol oral solution. Nine sites in the U.S. have been activated for screening and patient recruitment. The drug has also received Orphan Drug Designation and Fast Track designation by the FDA.

REGENXBIO completed enrollment in Cohort 5 of its Phase II AAVIATE study of RGX-314 for wet age-related macular degeneration (wet AMD) using in-office suprachoroidal delivery. Being developed with AbbVie, RGX-314 is a potentially one-time treatment for wet AMD, diabetic retinopathy, and other chronic retinal diseases. The drug is made up of the NAV AAV8 vector that encodes an antibody fragment that inhibits vascular endothelial growth factor (VEGF). The company licensed certain exclusive rights to the SCS Microinjector from Clearside Biomedical to deliver gene therapies directly to the suprachoroidal space of the eye.

Moleculin Biotech reported preliminary data from the second cohort of its Phase Ia trial of WP1122. The cohort was made up of eight subjects dosed with 16 mg/kg or placebo in the dose-escalation study evaluating the safety and pharmacokinetics of the drug in healthy volunteers in the U.K. The drug is being evaluated as a treatment for COVID-19. WP1122 was developed as a 2-DG prodrug and was found to have greater potency than 2-DG alone in preclinical models where tumor cells require higher glycolytic activity than normal cells. It has also demonstrated greater antiviral effects than 2-DG against SARS-CoV-2 in MRC-5 cell cultures.

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