Clinical Catch-Up: March 22-26
There was a fair amount of clinical trial news last week. Here’s a look.
AstraZeneca reported that the U.S. Phase III trial of the vaccine, AZD1222, demonstrated an efficacy of 79% at preventing symptomatic COVID-19 and 100% efficacy at preventing severe disease and hospitalization. The announcement was on interim analysis based on 32,449 participants in the trial reporting 141 symptomatic cases of COVID-19. Efficacy was consistent across all ethnicities and age, and in participants 65 years of age and older, efficacy was 80%.
Two days later, the company released primary analysis that the vaccine demonstrated 76% efficacy against symptomatic COVID-19, 100% efficacy against severe or critical disease and hospitalizations, and 85% efficacy against symptomatic COVID-19 in people 65 years and older.
Regeneron reported that its REGEN-COV antibody cocktail (casirivimab with imdevimab) decreased the risk of hospitalization or death by 70% in non-hospitalized COVID-19 patients. This cut the duration of symptoms by four days. They found that all doses, 8,000 mg, 2,400 mg and 1,200 mg, had similar efficacy. The therapeutic also hit all secondary endpoints in the Phase III outcomes study, including reduction of symptom duration. A companion Phase II trial demonstrated that even the lowest doses tested, 300-mg intravenous and 600-mg subcutaneous, had significant decreases in viral load over the first seven days of the study, comparable to the 2,400-mg and 1,200-mg intravenous doses.
Pfizer announced it is launching a single ascending dose-ranging Phase I study in healthy adults, testing its investigational, novel oral antiviral against SARS-CoV-2. The trial will be run in the U.S. The drug, PF-07321332, is a SARS-CoV2-3CL protease inhibitor and has shown potent anti-viral activity in laboratory assays against SARS-CoV-2, as well as against other coronaviruses. The company is also investigation an intravenously administered protease inhibitor, PF-07304814, currently in a Phase Ib trial in hospitalized COVID-19 patients.
Kaleido Biosciences reported positive data from a non-IND study of KB109 in patients with mild-to-moderate COVID-19. The analysis showed a decrease in overall COVID-19 related healthcare utilization, which they defined as hospitalizations, emergency room visits, and urgent care visits. The trial also demonstrated a significant decrease in recovery time for patients 45 years of age and older or with one or more comorbidities who received KB109 and self-supportive care compared to patients with self-supportive care alone. KB109 is a novel, oral product based on the company’s Microbiome Metabolic Therapy (MMT) platform.
Moderna recently dosed the first participants in a Phase I study of their next-generation COVID-19 vaccine. The vaccine is dubbed mRNA-1283. It appears to be refrigerator stable—the first-generation vaccine requires cold-chain storage, although not as cold as the Pfizer-BioNTech vaccine—and a single dose instead of the current two-dose regimen. They’re also testing it as a two-dose regimen. They’re also evaluating mRNA-1283 as a booster with the current vaccine to determine if it will increase protection.
Researchers at the University of California, San Diego (UCSD) have initiated a clinical trial to determine if certain types of mushrooms can help treat early-stage COVID-19. There are approximately 12,000 known species of mushrooms and the research project will focus on turkey tail and agarikon, both native to old growth North American forests—neither have hallucinogenic properties. In lab studies, agarikon demonstrated strong antiviral activity against resistant strains of tuberculosis and H1NA (swine flu), H5N1 (bird flu), cowpox and herpes viruses. In some assays, agarikon were 10 times more potent against fluviruses than the antiviral drug ribavirin. The study is recruiting 132 volunteers recently diagnosed with COVID-19. It will be conducted at UCSD and UCLA.
Roche’s checkpoint inhibitor Tecentriq (atezolizumab) hit the mark in the company’s Phase III IMpower010 trial of the drug compared to best supportive care (BSC) in people with resectable early-stage lung cancer. The primary endpoint was disease-free survival (DFS) at the interim analysis. The drug showed a statistically significant improvement in DFS as adjuvant therapy after surgery and chemotherapy in all randomized Stage II-IIIA populations with non-small cell lung cancer (NSCLC). There was a pronounced benefit in the PD-L1-positive population.
89bio presented additional data from its positive Phase Ib/IIa trial of BIO89-11 in nonalcoholic steatohepatitis (NASH). BIO89-100 is a long-acting glycoPEGylated FGF21 analog.
BioCryst Pharmaceuticals announced that its BCX9930 significantly increased hemoglobin and decreased transfusions in an ongoing dose-ranging trial in treatment-naïve paroxysmal nocturnal hemoglobinuria (PNH) patients, and in PNH patients with an inadequate response to C5 inhibitors. BCX9930 is an oral Factor D inhibitor.
Fractyl Laboratories enrolled the first patient in its pivotal clinical trial of Revita DMR for type 2 diabetes. The trial, REVITA-T2Di is a prospective, randomized, double-blind, sham-controlled study that will enroll more than 300 patients at up to 35 sites in the U.S. and Europe. Revita DMR is an outpatient endoscopic procedure that resurfaces the lining of the upper intestine.
Genentech published positive Phase I data on glofitamab for CD20-positive B-cell blood cancers. Glofitamab is a novel, bivalent CD-20 targeting T-cell engaging-bispecific antibody. It induced complete remissions in r/r B-cell lymphoma.
Chiasma presented new positive data from its MPOWERED Phase III trial of MYCAPSSA. The drug improved clinical symptoms and other patient-reported outcomes compared to long-acting injectable somatostatin receptor ligands in patients with acromegaly.
Amolyt Pharma presented positive data from the first cohorts of the single ascending dose portion of its Phase I trial in healthy volunteers of AZP-3601 for hypoparathyroidism. AZP-3601 is a therapeutic peptide that targets a specific conformation of the parathyroid hormone receptor.
Ionis Pharmaceuticals announced that its collaboration partner, Roche, was discontinuing dosing in the Phase III GENERATION HD1 trial of tominersen in manifest Huntington’s disease (HD). No new safety signals were observed, the decision was made on data from a pre-planned review from the Phase III trial run by an unblinded Independent Data Monitoring Committee (iDMC). The recommendation was related to the drug’s potential benefit/risk profile for patients.
In addition to the GENERATION HD1 trial, they are pausing dosing in the open-label extension study, GEN-EXTEND, while they pore over the data to determine the next steps. However, Roche has said that the Phase I PK/PD study, GEN-PEAK, of tominersen and Roche’s observational HD Natural History Study will continue as planned. Tominersen, previously IONIS-HTTRx or RG6042, is an antisense therapy engineered to decrease the production of all types of the huntingtin protein (HTT), including the mutated variant, mHTT. Roche licensed the drug from Ionis in December 2017.
Precigen dosed the first patient in its Phase I trial of PRGN-2012 for recurrent respiratory papillomatosis (RRP). PRGN-2012 is a first-in-class, off-the-shelf AdenoVerse immunotherapy.
Myovant Sciences and Pfizer announced positive results from the Phase III LIBERTY trial of relugolix combination therapy in women with uterine fibroids. The combination therapy is made up of relugolix 40 mg plus estradiol 1.0 mg and norethindrone acetate 0.5 mg. The trial was designed to evaluate continued treatment with the relugolix combo for up to two years.
This particular study, the LIBERTY randomized withdrawal study, was a Phase III trial that enrolled eligible women who completed the LIBERTY long-term extension study. The criteria for eligibility included meeting the responder criteria at one year. Responder criteria were defined as a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction from baseline in menstrual blood loss volume during the last 35 days of treatment measured by the alkaline hematin method.
Theratechnologies dosed the first patient in its Phase I trial of TH1902 for sortilin positive (SORT1+) solid tumors. TH1902 combines the company’s proprietary peptide to docetaxel.
Intensity Therapeutics, The Ottawa Hospital and Ontario Institute for Cancer Research inked an agreement to run a Phase II Window of Opportunity (WOO) trial of INT230-6 compared to no treatment in early-stage breast cancer. WOO studies are where patients receive a test drug or drugs between their cancer diagnosis and standard treatment (usually surgery), in order to expedite analysis of therapeutic agents and focused biomarker research. INT230-6 is made up of two proven, potent anti-cancer agents, cisplatin and vinblastine, and a penetration enhancer molecule that helps disperse the drugs throughout tumors for diffusion into cancer studies.
Enterome SA received the go-ahead from the FDA to launch a Phase I/II trial of EO2463 for non-Hodgkin B-cell lymphomas. EO2463 is an innovative, off-the-shelf immuno-oncology candidate that combines four OncoMimics of B lymphocytes-specific lineage markers. Oncomimics are peptides, derived from bacteria in the gut microbiome, that closely mimic either overexpressed tumor-associated antigen (TAA) or lineage-specific markers in solid and liquid tumors, respectively.
Guerbet announced positive results from two Phase III trials comparing the diagnostic efficacy and safety of Gadopiclenol to Gadobutrol in a wide range of indications, covering the CNS and various other areas, including head and neck, thorax, abdomen, pelvis, and musculoskeletal system. Gadopiclenol is a new macrocyclic gadolinium-based contrast agent with high contrast power.
Visus Therapeutics initiated its Phase II trial of Brimochol for presbyopia, the loss of near vision associated with aging. Brimochol is a topical ophthalmic solution, a pupil-modulating product that combines two FDA-approved drugs, carbachol, a cholinergic agent, and brimonidine tartrate, an alpha-2 agonist.
Attgeno dosed the first patient in its Phase I trial of Supernitro for lung injury. Supernitro is an intravenous, ultra-short half-life rapidly releasing formulation that includes nitric oxide.