GRF-6021

It was another busy week for clinical trial announcements. Here’s a look. COVID-19-Related CytoDyn announced that its Phase III trial of Vyrologix (leronlimab-PRO 140) demonstrated continued safety, substantial improvement in the survival rate, and faster hospital discharge in critically ill COVID-19 patients. The drug is a CCR5 antagonist being developed for several indications, including HIV and metastatic triple-negative breast cancer. The company also announced that 20 patients had been enrolled and dosed in the first 10 days of its Phase II trial for COVID-19 long-haulers syndrome. The trial will enroll 50 patients. Novavax announced that its COVID-19 vaccine had final efficacy of 96.4% against mild, moderate and severe COVID-19 caused by the original Wuhan wildtype strain in its UK pivotal Phase III trial. And after completing analysis of its Phase IIb trial in South Africa, it reported 55.4% efficacy among the HIV-negative trial volunteers in an area where the majority of strains were the South African B1.351 variants. Perhaps most importantly, across both trials, the Novavax vaccine was 100% protective against severe disease, including hospitalizations and death. Sanofi Pasteur and Translate Bio initiated their Phase I/II clinical trial of MRT5500, a messenger RNA (mRNA) vaccine candidate against COVID-19. The Phase I/II trial will include a total of 415 healthy adults 18 years of age and older and be enrolled across 13 sites. It requires two doses, 21 days apart. They will evaluate three different dose levels, 15 micrograms, 45 micrograms and 135 micrograms. Quantum Leap Healthcare Collaborative (QLHC) announced it will not continue with further testing of Aerpio Pharmaceuticals’ razuprotafib, which was part of the I-SPY COVID Trial. It is a Phase II adaptive trial that is testing various drugs that show promise of reducing the risk of death from and severe illness in COVID-19. The sponsor indicated the drug was challenging to administer in the COVID-19 setting, with 30% discontinuing the drug because of disease-related hypotension, including protocol-mandated stopping rules. There was no indication the drug caused the hypotension, but it was determined there was a small but clinically significant drop in systolic blood pressure and mean arterial blood pressure. Merck and Ridgeback Biotherapeutics announced preliminary results from Ridgeback’s Phase IIa trial of molnupiravir in COVID-19. They reported on one secondary objective, demonstrating a decrease in days to negativity of infectious virus isolation in nasopharyngeal swabs, as determined by isolation in Vero cell line culture. Molecular Partners AG and Novartis announced initial data from their ongoing Phase I trial of their tri-specific COVID-19 antiviral drug, ensovibep, in healthy volunteers. In the study, healthy volunteers were randomized 3:1 to receive an infusion of ensovibep or placebo, respectively. In both cohorts of two different doses of the drug, 3mg or 9mg per kilogram body weight, the drug was observed to be safe and well tolerated with no significant adverse events. The drug is designed to target multiple different sites on the SARS-CoV-2 virus simultaneously. It is formatted with a half-life extending DARPin domain that binds to human serum albumin (HSA) to support long-acting activity. Genentech, a Roche company, announced that its Phase III REMDACTA trial of Actemra (tocilizumab) plus Gilead Sciences’ Veklury (remdesivir) compared to placebo plus Veklury, failed to meet its primary endpoint in patients with severe COVID-19 pneumonia. The endpoint was measured by improved time to hospital discharge up to day 28 in this patient group receiving standard of care. Actemra is a humanized interleukin-6 (IL-6) receptor antagonist indicated for adults with moderately to severely active rheumatoid arthritis who have used one or more antirheumatic drugs, such as methotrexate, that did not provide enough relief. Vir Biotechnology and GlaxoSmithKline announced that an independent Data Monitoring Committee (IDMC) recommend their Phase III COMET-ICE trial of VIR-7831 as a monotherapy for early treatment of COVID-19 in adults at high risk be stopped for enrollment “due to evidence of profound efficacy.” The recommendation was based on interim analysis of data from 583 patients in the trial showing an 85% decrease in hospitalization or death in patients receiving the drug alone compared to placebo, which was the primary endpoint of the trial. The drug was well tolerated. VIR-7832 is an investigational dual-action SARS-CoV-2 monoclonal antibody. It appears to both block viral entry into healthy cells and improves the ability to clear infected cells. The antibody binds to an epitope on SARS-CoV-2 that is shared with SARS-CoV-1, the virus that causes SARS, suggesting it is highly conserved, and hopefully will make it more difficult for resistance to develop. Persephone Biosciences initiated the VOICES clinical study to determine the impact of gut microbiome composition and function on the immune system and efficacy of COVID-19 vaccination. The trial will enroll up to 10,000 people in the U.S being administered a COVID-19 vaccine. Blood and stool samples will be collected before and after the vaccinations with the goal of identifying and determining specific gut microbiota and the metabolic processes involved in optimal immune response and function. Rigel Pharmaceuticals completed patient enrollment in its Phase II trial of fostamatinib in hospitalized COVID-19 patients. Fostamatinib is an oral spleen tyrosine kinase (SYK) inhibitor marketed in the U.S. as Tavalisse for adult chronic immune thrombocytopenia. Non-COVID-19-Related Mayne Pharma presented new data showing treatment with NEXTSTELLIS resulted in limited changes in endocrine markers, including lower increases in hormone-binding globulins, compared with combined oral contraceptives (COCs) based on etinyl-estradiol (EE), the synthetic estrogen used in all but one of the marketed COCs. NEXTSTELLIS is a novel COC containing drospirenone (DRSP) and estetrol (E4). Novartis announced that the Phase III CANOPY-2 trial of canakinumab failed to meet the primary endpoint of overall survival (OS). The drug was being evaluated in 237 adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose disease progressed while on or after previous platinum-based chemotherapy and checkpoint inhibitor immunotherapy. Canakinumab is a human monoclonal antibody that binds to human interleukin-1 and neutralizes its activity. By neutralizing IL-1beta, preliminary data suggested the drug would inhibit pro-tumor inflammation, improve anti-tumor immune response, decrease tumor cell proliferation, survival and invasiveness, and impair angiogenesis. The company plans to continue to analyze the data. Two Phase III CANOPY studies are continuing, testing the drug in first-line and adjuvant settings. ViiV Healthcare, majority-owned by GlaxoSmithKline, with Pfizer and Shionogi as shareholders, presented positive data from its Phase IIa proof-of-concept study of GSK-254 in HIV. The drug is an investigational maturation inhibitor. It demonstrated a relationship between dose and antiviral response with the 140mg and 200mg doses showing the greatest reduction in plasma HIV-1 RNA. Orca Therapeutics announced the independent Data and Safety Monitoring Board had reviewed its ongoing Phase I/IIa trial of ORCA-010 in treatment-naïve patients with localized prostate cancer and recommended continuation without modification. ORCA-010 is derived from the common cold virus adenovirus serotype 5 (Ad5) and then its DNA was modified in three places. TG Therapeutics published results from the UNITY-NHL Phase IIb trial of Ukoniq (umbralisib) in r/r indolent non-Hodgkin Lymphoma. The drug is a PI3k-delta and CK1-epsilon inhibitor. Clene and its subsidiary Clene Nanomedicine announced more than 50% of participants had been enrolled in the HEALEY ALS Platform Trial. It is a multi-center trial evaluating the safety and efficacy of multiple products in amyotrophic lateral sclerosis (ALS). CNM-Au8 was selected. It is a bioenergetic nanocatalyst, a stable, aqueous suspension of catalytically active gold (Au) nanocrystals. ORYZON Genomics presented new data from its Alzheimer’s trials with vafidemstat, ETHERAL and REIMAGINE-AD. The data confirmed previous findings on the safety of vafidemstat in these patients and its efficacy in controlling aggression and agitation. The drug modulates the histone-modifying enzyme LSD1. AEON Biopharma initiated enrollment in its Phase II trial of ABP-450 for the prevention of migraines. The drug contains a 900 kDa botulinum toxin type-A complex. Alkahest and a subsidiary of Grifols, presented data on its study of GRF6021 in Parkinson’s disease. The drug is a therapeutic plasma fraction candidate. Aravive dosed the first patient in its open-label Phase Ib/II trial of AVB-500 in advanced clear cell renal cell carcinoma patients that have progressed on front-line treatment. AVB-500 is an ultra-high affinity decoy protein that targets the GAS6-AXL signaling pathway associated with tumor cell growth. Merck presented results from a Phase I study of islatravir for pre-exposure prophylaxis of HIV-1 infection. Islatravir is a nucleoside reverse transcriptase translocation inhibitor. As a result, the company plans to initiate a Phase II trial. bluebird bio announced further analysis from its Phase I/II trial of LentiGlobin for sickle cell disease in regards to a case of acute myeloid leukemia (AML) that placed the study on clinical hold in February. Another patient in the study had also developed myelodysplastic syndrome. The new analysis indicated that the gene therapy was unlikely to be the cause of the AML. Aelix Therapeutics presented topline results from the Phase I/IIa AELIX-002 trial of its HTI T-cell therapeutic HIV vaccine in early-treated people living with HIV. The trial met its primary and secondary endpoints for safety, tolerability and immunogenicity. The data also suggested encouraging efficacy data. Transgene expanded its Phase II trial of TG4001 in combination with avelumab compared to avelumab monotherapy in patients with HPV16-positive anogenital cancers. The amendment allows a more rapid start. TG4001 is an investigational therapeutic vaccine based on a non-propagative, highly attenuated Vaccinia vector (MVA) engineered to express HPV16 antigens E6 and E7 and an adjuvant (IL-2). Aligos Therapeutics began dosing the first cohort of chronic hepatitis B patients in its ongoing ALG-010133-101 study of ALG-010133. The drug is a proprietary olignonucleotide S-antigen Transport-inhibiting Olignonucleotide Polymer (STOPS) molecule that was developed to reduce viral S-antigen levels in hepatitis B patients. Agenus presented data on its Phase I/II trial of AGEN1181 in tumors previously unresponsive to immune therapies. AGEN1181 is the company’s Fc-enhanced next-generation anti-CTLA-4 antibody. The therapy was active even in patients with the low affinity FcyRIIIA allele and the drug demonstrated the ability to deplete intatumoral Tregs. Biohaven Pharmaceutical announced that more than 50% of participants had been enrolled in the verdiperstat regimen of HEALEY ALS Platform Trial, which is testing the efficacy of several treatments in amyotrophic lateral sclerosis (ALS). Verdipistat is a potential first-in-class, brain-penetrant, selective inhibitor of myeloperoxidase. Nouscom received approval from the regulatory authorities in Spain to launch a Phase Ib trial of NOUS-PEV. NOUS-PEV is a personalized cancer immunotherapy that will be evaluated in either locally advanced 1L melanoma or 1L non-small cell lung cancer (NSCLC). AVEO Oncology announced they had inked a clinical trial collaboration and supply deal with Bristol Myers Squibb to study Fotivda in combination with BMS’s checkpoint inhibitor Opdivo (nivolumab) in advanced r/r RCC after previous immunotherapy exposure. Earlier in the week, the FDA approved Fotivda for adults with relapsed or refractory advanced renal cell carcinoma (RCC) in people who have had two or more previous systemic therapies. The drug is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).