Clinical Catch-Up: 7 Deaths Halt MacroGenics' Cancer Trial, Exelixis Shines in RCC

In the dog days of summer, companies are busy announcing clinical trial news. Take a look at some of last week’s most interesting clinical announcements.

MacroGenics shuttered a Phase II trial of enoblituzumab in combination with retifanlimab or tebotelimab as first-line treatment for recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) after seven reported deaths. Enoblituzumab is an anti-B7-H3 monoclonal antibody. Both retifanlimab and tebotelimab are anti-PD-1 checkpoint inhibitors. Six of the seven deaths were “secondary to disease progression and/or unrelated to the study treatment.” However, the seventh is believed to be related to the drugs used. The deaths were hemorrhagic in origin, which is known to be associated with these types of cancers, but their rates were much higher than reported in the medical literature.

Exelixis announced that its Phase III COSMIC-313 Trial hit the primary endpoint, demonstrating significant improvement in progression-free survival (PFS). The study is evaluating the combination of Cabometyx (cabozantinib), Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) compared to the combination of nivolumab and ipilimumab in patients with previously untreated advanced intermediate- or poor-risk renal cell carcinoma (RCC). Cabometyx is a tyrosine kinase inhibitor approved for RCC.

Aquestive Therapeutics announced positive topline data from the final two arms of Part 3 of the EPIPHAST study for AQST-109 epinephrine oral film. The trial is evaluating the administration of the film under different conditions. In this case, peanut allergy. The data demonstrated that administering the film sublingually two minutes after eating a peanut butter sandwich had no statistical impact on the resulting pharmacokinetics compared to previous data from the initial Part 3 dataset. The medium time to maximum concentration and partial area under the curve data were comparable, and the time to reach maximum concentration (Tmax) remained twelve minutes.

scPharmaceuticals announced positive results from the AT HOME-HF Pilot Phase II study of FUROSCIX (furosemide 80 mg/10 mL for S.Q. administration) for heart failure. The study enrolled 41 patients, 34 of whom received FUROSCIX and 17 received “treatment as usual.” The patients had chronic heart failure who presented to a heart failure clinic with worsening congestion and requiring augmented diuresis. There was a positive trend in the Finkelstein-Schoenfeld win ratio of the hierarchal primary composite endpoint consisting of cardiovascular death, heart failure hospitalizations, emergency department visits for heart failure and percent change from baseline of NT-proBNP at day seven.

Edgewise Therapeutics initiated enrollment of the Phase II CANYON trial of EDG-5506 for people with Becker Muscular Dystrophy (BMD). EDG-5506 is an oral small molecule myosin modulator designed to protect injury-susceptible fast skeletal muscle fibers in dystrophinopathies. The trial will evaluate the drug over 12 months and expects to recruit about 66 people at up to 14 sites in the U.S., U.K. and Netherlands. BMD is a serious, progressively debilitating and potentially fatal inherited X-linked neuromuscular disorder caused by a dystrophin gene mutation.

Endevica Bio dosed the first patient in its Phase I trial of TCMCB07 for cachexia. TCMCB07 is a melanocortin‐4 antagonist peptide. Cachexia is a life-threatening aspect of many diseases, including lack of appetite and loss of muscle disproportionate to the decrease in caloric intake. It is associated with cancer, renal failure and congestive heart failure. The study will enroll up to 97 healthy volunteers, with data expected in the first quarter of 2023.

Pluristem Therapeutics announced topline results from its Phase III trial of allogeneic PLX-PAD cells for muscle injury after arthroplasty for hip fracture. The study enrolled 240 patients in the U.S., Europe and Israel. PLX-PAD was shown to effectively accelerate muscle strength and regeneration. However, the study did not meet the primary endpoint, which was the Short Physical Performance Battery (SPPB) test at week 26.

Regeneron Pharmaceuticals and Sanofi announced positive results from a Phase III trial of Dupixent (dupilumab) in kids ages one to 11 years with eosinophilic esophagitis (EoE). EoE is a chronic inflammatory illness that causes damage to the esophagus, which prevents it from working effectively. The study hit the primary endpoint of histological disease remission at 16 weeks with both higher and lower dose weight-tiered dosages. There was an 86% decrease in peak esophageal intraepithelial eosinophil count from baseline compared to a 21% increase for placebo. The study demonstrated a 3.5-point decrease in abnormal endoscopic findings from baseline compared to 0.3 points increase for placebo.

CANbridge Pharmaceuticals dosed the first patient in China in the Phase II EMBARK study of CAN108 (maralixibat) in biliary atresia. The trial will evaluate the drug in patients with B.A. after Kasai surgery. It is expected to enroll up to 20 patients in China and 72 patients globally. CANbridge and Mirum Pharmaceuticals have an exclusive license deal for the drug in Greater China. The drug (Livmarli) is an oral, once-daily, ileal bile acid transporter inhibitor. It is approved in the U.S. for cholestatic pruritus in patients with Alagille syndrome one year of age and older.

SaNOtize Research & Development Corp. published data from a Phase III trial of its nitric oxide nasal spray (NONS) for adults with COVID-19. Starting treatment within three days of a positive test, viral load was decreased by about 94% within 24 hours and 99% within 48 hours in patients at higher risk of disease progression. The research was published in The Lancet Regional Health Southeast Asia. Nitric oxide blocks entry into cells of the nasal passage, kills the virus and halts its replication.