Clinical Catch-Up: August 31-September 4
It was a busy week for both COVID-19-related clinical trial news and the rest of the industry. Here’s a look.
COVID-19-Related
Vir Biotechnology and GlaxoSmithKline dosed the first patient last week in a Phase II/III clinical trial of VIR-7831, a fully human monoclonal antibody against COVID-19. The trial is evaluating therapy as early treatment for COVID-19 patient at high risk of hospitalization. The Vir-GSK COMET-ICE study plans to enroll about 1,300 patients globally who have early symptoms of infection. The goal is to evaluate VIR-7831, a single-dose monoclonal antibody, to see if it can prevent hospitalization from the disease. They expect results before the end of the year with complete data in the first quarter of 2021, and possibly early access to treatment in the first half of 2021.
FSD Pharma submitted an IND for FSD201 (ultramicronized palmitoylethanolamide, or ultramicronized PEA) to treat COVID-19. FSD201 is being developed for its anti-inflammatory properties to avoid the cytokine storm linked with acute lung injury in hospitalized COVID-19 patients. The Phase II trial will be run at 25 to 30 sites in North America.
Orpheris, a subsidiary of Ashvattha Therapeutics, enrolled the first patients in its Phase II PRANA clinical trial of OP-101 in severe COVID-19. OP-101 is designed to target and shut down all proinflammatory pathways and restore macrophages to a normal, anti-inflammatory state.
AstraZeneca announced that its Phase III clinical trial of its COVID-19 vaccine candidate, AZD1222, is expanding into the U.S. It will be dubbed D8110C00001 and is funded by the Biomedical Advanced Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases (NIAID). The NIAID-supported COVID-19 Prevention Network (CoVPN) is also participating. The U.S. expansion will recruit up to 30,000 adults over the age of 18 years from a broad range of racial, ethnic and geographic groups who are healthy or have stable underlying medical conditions. This will also include patients with HIV, who are at increased risk from COVID-19 infections.
Clear Creek Bio dosed the first patient in a Phase I clinical trial of brequinar in COVID-19 patients. Brequinar is an oral, potent and selective small molecule DHODH inhibitor that blocks host cell de novo pyrimidine biosynthesis, which is needed for DNA and RNA synthesis. It appears to have potent antiviral activity.
Biophytis enrolled the first patient in COVA, a Phase II/III trial of sarconeos (BIO101) for patients with COVID-19-related respiratory failure. It has five centers recruiting patients in Belgium, France and the U.S. Sarconeos is an oral small molecule being developed in Phase IIb in sarcopenia, as well as Duchenne muscular dystrophy (DMD). The drug activates the MAS receptor, a key component of the protective arm of RAS, the renin angiotensin system, which plays a key role in regulating respiratory function.
Sanofi announced that its Phase III trial of IV Kevzara (sarilumab) at a dose of 200mg or 400mg in severely or critically ill patients hospitalized with COVID-19 did not meet its primary endpoint and key secondary endpoint compared to placebo. Kevzara is approved to treat adults with moderately to severely active rheumatoid arthritis. It binds to the IL-6b receptor and inhibits IL-6 mediated signaling.
INmune Bio got the go-ahead from the FDA to initiate a Phase II trial of Quellor, a selective soluble tumor necrosis factor (sTNF) inhibitor, for the immune mediated complications in COVID-19 patients. The blinded randomized Phase II trial will enroll 366 COVID-19 patients in two equal sized cohorts, standard of care, which may include remdesivir, or SOC plus Quellor. A second dose of Quellor may be given a week later if the patient remains hospitalized.
Organicell Regenerative Medicine reported that the FDA granted emergency, expanded access to treat two mild to moderate COVID-19 patients and one “long hauler” post COVID-19 patient with Zofin. The company plans to begin patient enrollment in a Phase I/II trial to evaluate the drug in moderate to severe COVID-19 patients. Zofin is a nanoparticle-based therapy derived from perinatal sources and designed to retain microRNAs.
Aerpio Pharmaceuticals and Quantum Leap Healthcare Collaborative dosed the first patient with razuprotafib in the Phase II I-SPY COVID Trial in hopes of improving ARDs in severely ill COVID-19 patients. Razuprotafib is a first-in-class small molecule inhibitor of vascular endothelial protein tyrosine phosphatase and is also being developed for open angle glaucoma and other indications.
City of Hope is initiating a Phase I trial of rheumatoid arthritis drug leflunomide in COVID-19 patients. Patients treated for cancer in the last two years may also be eligible. The overall focus is on cancer patients who are being treated for COVID-19.
GlaxoSmithKline and Sanofi are beginning a Phase I/II clinical trial of their COVID-19 vaccine that uses GSK’s pandemic adjuvant technology. It will include 440 healthy adults be run at 11 separate sites.
Non-COVID-19-Related
AstraZeneca’s Farxiga (dapagliflozin) dramatically prolonged survival in patients with chronic kidney disease in a Phase III clinical trial. Specifically, Farxiga with standard of care decreased the composite measure of worsening of renal function or risk of cardiovascular (CV) or renal death by 39% compared to placebo. This was in patients with chronic kidney disease (CKD) Stages 2-4 and elevated urinary albumin excretion. There were no differences observed in patients who had or did not have type 2 diabetes.
Akcea Therapeutics and Ionis Pharmaceuticals presented data from the Phase II study of AKCEA-APOCIII-LRx. The therapy met primary and key secondary endpoints with significant decreases in triglyceride and apoC-III levels. AKCEA-APOCIII-LRx is designed using Ionis’ Ligand Conjugated Antisense (LICA) technology platform to inhibit production of apolipoprotein C-III, a protein generated in the liver that plays a primary role in the regulation of serum triglycerides.
UCB published the results of the Phase III VIMPAT (lacosamide) CV as adjunctive treatment for uncontrolled primary generalized tonic-clonic seizures (PGTCS). The trial enrolled 242 patients with idiopathic generalized epilepsy. The primary endpoint was time to second PGTCS during the 24-week treatment period. Treatment with locasamide demonstrated a significantly lower risk of developing a second PGTCS and a significantly higher rate of freedom from PGTCS during the period compared to placebo. It was approved in the U.S. in 2008 as an add-on therapy for adult patients, then as a monotherapy in adults in August 2014, and in 2018, as monotherapy or adjunctive therapy in patients four years of age and older with partial-onset seizures.
Eisai announced data from several post hoc analyses of Dayvigo from the Phase III SUNRISE 1 and 2 trials and topline results from an open label pilot study. The studies evaluated the transition of insomnia patients from zolpidem to Dayvigo, with generally positive results. Dayvigo (Lemborexant) is a small-molecule orexin receptor antagonist.
Novartis announced results from a post-hoc analysis of pooled data from the Phase III ORION-10 and -11 trials evaluating individual responses of patients on low-density lipoprotein cholesterol reduction with inclisiran. Inclisiran is a first-in-class investigation treatment for hyperlipidemia in adults. The new data showed a highly consistent effect with a similar safety profile to placebo.
Boehringer Ingelheim and Eli Lilly announced full results from the EMPEROR-Reduced Phase III trial in adults with heart failure with reduced ejection fraction, with and without diabetes. This showed that Jardiance (empagliflozin) was associated with a 25% relative risk reduction in the primary endpoint of time to cardiovascular death or hospitalization due to heart failure.
Acasti Pharma announced topline data from its Phase III TRILOGY 2 trial of CaPre (omega-3 phospholipid) to reduce severe triglyceride levels. The primary endpoint was triglyceride reduction at 12 and 26 weeks. The trial evaluated 278 patients. Patients receiving CaPre demonstrated a 30.4% median reduction in triglyceride levels compared to 30.5% in TRILOGY 1, and a 17.9% median reduction in triglyceride levels in patients receiving placebo at 12 weeks compared to 27.5% in TRILOGY 1. The company indicated that the unadjusted, placebo corrected triglyceride reduction of 12.4% achieved a “p” value of 0.19, which was not statistically significant—as a result, TRILOGY 2 did not meet the primary endpoint.
Mirum Pharmaceuticals presented new data from its Phase II INDIGO trial. It was a five-year analysis that demonstrated that patients with PFIC2, also called bile salt export pump (BSEP) deficiency, who achieved serum bile acid (sBA) control on long-term maralixibat treatment have a significant improvement in transplant-free survival.
Bristol Myers Squibb announced interim data from the Phase III open-label extension trial DAYBREAK. The data demonstrated the long-term efficacy and safety profile of Zeposia (ozanimod) in relapsing forms of multiple sclerosis (MS). The trial included 2,494 patients who had previously completed a Phase I, II or III Zeposia trial and who had an average treatment time of 35.4 months while in DAYBREAK. No new safety concerns were observed. At 2 and 3 years, 79% and 75% of patients, respectively, were relapse-free and 3- and 6-month confirmed disability progression was observed in 10.8% and 8.6% of participants, respectively.
Oxurion NV dosed the first patient in its two-part Phase II trial KALAHARI. It is evaluating THR-149 for the treatment of diabetic macular edema (DME). THR-149 acts via inhibition of the Plasma Kallikrein-Kinin (PKal-Kinin) system, a validated VEGF independent target for DME.
Janssen Pharmaceutical of Johnson & Johnson made a strategic call to halt development of pimodivir, an antiviral treatment for influenza A. The decision was based on data from a pre-planned interim analysis of the Phase III trial of pimodivir in hospitalized influenza A patients. The analysis suggested that the drug in combination with standard of care (SOC) was “very unlikely” to show added benefit in the patient population over SOC alone.
Akebia Therapeutics announced topline results for PRO2TECT, the second of two Phase III cardiovascular outcomes programs. The trial was evaluating the company’s vadadustat for treatment of anemia caused by chronic kidney disease in adults not on dialysis. In the two PRO2TECT studies, vadadustat hit the primary and key secondary efficacy endpoint, which was non-inferiority to darbepoetin alfa. This was measured by a mean change in hemoglobin (Hb) between baseline and the primary evaluation period, weeks 24 to 36 and the secondary evaluation period at weeks 40 to 52.
However, the drug did not meet the primary safety endpoint of the PRO2TECT program. This was defined as non-inferiority of vadadustat compared to darbepoetin alfa in how long to the first occurrence of major adverse cardiovascular events (MACE). MACE is the composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke.
Amylyx Pharmaceuticals published data from its Phase II/III CENTAUR clinical trial evaluating AMX0035 in amyotrophic lateral sclerosis (ALS). The research was published in the New England Journal of Medicine. The trial met its primary endpoint, showing a clinically meaningful and statistically significant treatment benefit based on the Revised ALS Functional Rating Scale (ALSFRS-R). The trial evaluated 137 people with ALS and was conducted at 25 medical centers in the U.S. through the Northeast ALS (NEALS) consortium. AMX0035 is a neuroprotective therapy designed to decrease neuronal death and dysfunction. It targets endoplasmic reticulum and mitochondrial dependent neuronal degeneration pathways in ALS.