Clinical Catch-Up: August 3-7
It was a moderately busy week for clinical trial news, with some particularly interesting announcements related COVID-19 vaccine trials. Here’s a look.
Russia’s minister of health, Mikhail Murashko, indicated that the country plans a nationwide program to vaccinate its population against COVID-19 starting in October. The vaccine has not yet completed clinical trials. Murashko indicated they would begin by vaccinating teachers and health care workers. There are doubts as to whether the country has sufficiently tested the vaccine.
Members of the COVID R&D Alliance, including AbbVie, Amgen and Takeda Pharmaceutical, enrolled the first patients in the I-SPY COVID Trial. The trial will evaluate the efficacy of cenicriviroc, a chemokine dual-receptor antagonist, Otezla (apremilast), a PDE4 inhibitor, and Firazyr (icatibant injection), a bradykinin B2 receptor antagonist in severely ill, hospitalized COVID-19 patients who require high-flow oxygen.
Partner Therapeutics signed a $35 million contract with U.S. Department of Defense for two clinical trials of inhaled Leukine (sargramostim, rhu-Granulocyte Macrophage-Colony Stimulating Factor) in patients with COVID-19 associated acute hypoxemia. They are expected to launch in August 2020 in the U.S. under an IND application approved by the FDA in May.
ANA Therapeutics’ IND application for ANA001 (niclosamide capsules) for COVID-19 received the go-ahead from the FDA. The trial will enroll at least 400 patients with COVID-19 at 10 centers in the U.S.
Biophytis received approval from the Brazilian Health Regulatory Agency (ANVISA) to begin its clinical development program COVA in Brazil. The COVA Phase II/III clinical program will evaluate the efficacy and safety of Sarconeos (BIO101) for respiratory deterioration in COVID-19 patients. Sarconeos is a small molecule, oral drug in Phase IIb trials for sarcopenia in the U.S. and Europe.
Novavax announced data from Phase I of its Phase I/II placebo-controlled trial of its vaccine with and without Matrix-M adjuvant. The trial was conducted in healthy adults 18 to 59 years of age. NVX-CoV2373 is a recombinant vaccine engineered from the genetic sequence of SARS-CoV-2. The company used its recombinant nanoparticle technology to create antigen derived from the virus’s spike (S) protein. It also contains the company’s saponin-based Matrix-M adjuvant to improve the immune response and stimulate high levels of neutralizing antibodies.
Everybody who received the vaccine developed IgG antibodies against the spike protein after a single dose, with many developing wild-type virus neutralizing antibody responses. After the second dose, 100% of participants developed wild-type virus neutralizing antibody responses. These results compared favorably to those seen in patients with clinically significant COVID-19. In particular, the company noted the IgG antibody response was highly correlated with neutralization titers, meaning that a significant percentage of them were functional.
Organicell Regenerative Medicine had two emergency INDs approved by the FDA for outpatient treatment of mild to moderate respiratory distress due to COVID-19. The first patient experienced moderate chest discomfort and received three doses of Organicell Flow, which reduced cough and improved ability to breathe without pain. The second outpatient received Bi-Level Positive Airway Pressure (BiPAP) treatment and after being treated as an outpatient, received Organicell Flow and reported improvements in all symptoms.
Merck KGaA, Darmstadt, Germany, is collaborating with the U.S. NIAID by contributing 3,000 units of Rebif (subcutaneous interferon beta-1a) for the Adaptive COVID-19 Treatment Trial 3 (ACCT 3). The trial is evaluating the use of Rebif with Gilead Sciences’ remdesivir compared to remdesivir alone in 1,000 hospitalized adultsl with COVID-19.
Immunic reported positive topline data from its Phase II EMPhASIS trial of IMU-838 in relapsing-remitting multiple sclerosis (RRMS). IMU-838 is the company’s lead product, a selective oral DHODH inhibitor. DHODH stands for the enzyme dihydroorotate dehydrogenase. In the EMPhASIS trial, IMU-838 hit all the primary and key secondary endpoints, indicating activity against RRMS. The primary endpoint demonstrated a statistically significant decrease in the cumulative number of combined unique active (CUA) magnetic resonance imaging (MRI) lesions up to week 24 in patients that received 45mg of IMU-838 once a day by 62% compared to placebo.
CymaBay Therapeutics announced positive topline data from ENHANCE, a Phase III trial of seladelpar for primary biliary cholangitis (PBC). Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta agonist.
Kadimastem’s AstroRx showed a positive efficacy signal and a good safety profile in Cohort B of the its Phase I/IIa trial in ALS. AstroRx is a cell therapy developed by Kadimastem and contains functional, healthy astrocytes derived from human Embryonic Stem Cells (hESC) that are targeted to protect diseased motor neurons through several mechanisms of action.
Biohaven Pharmaceutical enrolled the first patients in the HEALEY ALS Platform Trial. It is evaluating the efficacy of three treatments including verdiperstat in patients with amyotrophic lateral sclerosis (ALS). Verdiperstat is a potential first-in-class, brain-penetrant, selective inhibitor of myeloperoxidase.
AstraZeneca presented several trial results at the ATS (American Thoracic Society) Conference, including positive results from the Phase III ETHOS trial of Breztri Aerosphere for maintenance of COPD; Phase IIIb ANDHI trial data of benralizumab for severe, eosinophilic asthma; and results from the Phase IIb PATHWAY study of Tezepelumab on exacerbations in patients with severe uncontrolled asthma.
Nanospectra Biosciences added four more clinical trial sites to its ongoing AuroLase pivotal study. The extension study is evaluating the efficacy of using MRI/ultrasound fusion imaging technology to direct focal ablation of prostate tissue using nanoparticle-directed laser ablation. The four new sites are Duke University, Mayo Clinic, Northwell Health – Lenox Hill Hospital and Long Island Jewish Medical Center, and Huntsman Cancer Institute at the University of Utah.
REGENXBIO reported positive one-year data from patients in Cohorts 4 and 5 of the Phase I/IIa trial of RGX-314 for wet age-related macular degeneration (wet AMD). It plans to initiate a pivotal program for subretinal delivery of the drug in wet AMD by the end of 2020. The company also announced a Phase II trial of the drug for wet AMD delivered to the suprachoroidal space (AAVIATE) is active and expected to enroll patients in this year’s third quarter. In the Cohort 4 and 5 data, the drug was generally well-tolerated at all dose levels and showed durable treatment effect and meaningful reductions in anti-VEGF treatment burden over one year.
Clovis Oncology treated the first patient in the Phase II portion of the LIO-1 trial of lucatinab and Bristol Myers Squibb’s checkpoint inhibitor Opdivo (nivolumab) for gynecologic cancers. Lucitanib is Clovis’ investigational angiogenesis inhibitor, including VEGF1-3.
Spark Biomedical provided a promising update on its SPARK/MUSC NOWS trial, which is testing the use of Spark’s Transcutaneous Auricular Neurostimulation (tAN) device for newborns, the Roo, to treat Neonatal Opioid Withdrawal Syndrome (NOWS). The tAN therapy delivers gentle electrical stimulation to cranial nerve branches on and around the newborn’s ear.
Immunomedics reported that its confirmatory Phase III ASCENT study showed treatment with Trodelvy significantly improved progression-free survival (PFS), compared to chemotherapy, in brain metastasis negative patients with metastatic triple-negative breast cancer (mTNBC) who have previously received at least two previous therapies. Also, patient enrollment has resumed for the Phase III TROPiCS-02 study of Trodelvy in HR+/human epidermal growth factor receptor 2-negative metastatic breast cancer.
Levo Therapeutics announced topline data from the Phase III CARE-PWS trial of LV-101 (intranasal carbetocin) for the treatment of Prader-Willi syndrome (PWS). LV-101 is a selective oxytocin-receptor agonist. The trial did not meet its primary outcome measures of the 9.6 mg dose, but statistical significance was hit with the 3.2 mg dose.
Lundbeck discontinued the Phase II trial of Lu AF11167 in patients with schizophrenia who are experiencing persistent negative symptoms. The decision was based on a futility interim analysis and decided the trial is unlikely to achieve statistical significance on its primary endpoint, mean change from baseline to week 12 on the Brief Negative Symptom Scale (BNSS). Lu AF11167 is a small molecule, potent and selective inhibitor of the phosphodiesterase 10A enzyme.
Tessa Therapeutics published results from two investigator-sponsored Phase I/II trials of CD30 CAR-T cell therapy in patients with r/r Hodgkin lymphoma. The patients showed a high rate of durable compete responses and very favorable safety profile.
Precigen Triple-Gene announced six-month follow-up data from the Phase I trial of INXN-4001 for heart failure. The drug is a multigenic investigational therapeutic candidate that uses a non-viral plasmid designed to constitutively express human SDF-1alpha, VEGF165, and S100A1 gene products. The infusions were tolerated well overall to the drug, but there was one serious adverse event that was believed to be related to the infusion procedure itself.