Clinical Catch-Up: March 16-20

Research

The COVID-19 pandemic is dominating the news cycle, even in terms of biopharma clinical trials, as various clinical trials are initiated for vaccines or to test approved or experimental drugs against the coronavirus that causes it. There are also other clinical trial updates as well, although some of this has slowed due to the cancellation or postponement of international medical conferences where the data was to be presented. Here's a look.

Moderna’s mRNA-1274, the vaccine for the novel coronavirus that causes COVID-19, began its Phase I clinical trial. mRNA-1273 is a mRNA vaccine that encodes for a prefusion stabilized form of the Spike (S) protein. It was chosen by Moderna researchers in collaboration with scientists at the NIAID Vaccine Research Center (VRC). The trial is being conducted at the Kaiser Permanente Washington Health Research Institute in Seattle. The first patient was dosed Monday, March 16. The trial will include 45 young, healthy volunteers who will receive different doses of the vaccine.

Gilead Sciences' clinical trials of antiviral drug remdesivir as a potential treatment for COVID-19 are ongoing, but a paper that demonstrated efficacy in treating the coronavirus is circulating prior to review that shows some potential concerns over safety. The specific paper describes three COVID-19 patients treated with remdesivir who “reported significant gastrointestinal symptoms” as well as elevated liver enzymes. There were no negative reports on efficacy.

CytoDyn filed a modified IND and protocol for its Phase II trial of leronlimab for patients who experience respiratory complications from COVID-19. Leronlimab is an investigational humanized IgG4 mAb that blocks CCR5. The modification of the IND came after the FDA responded to its original IND and protocol on March 9, 2020. On March 19, the FDA approved the IND.

Provention Bio temporarily paused the randomization of patients with newly diagnosed type 1 diabetes in its global Phase III PROTECT trial PRV-031. This is because of an abundance of caution over the COVID-19 pandemic. Teplizumab is an anti-CD3 monoclonal antibody. It has been shown to delay the onset of end-stage T1D in at-risk people with pre-symptomatic disease. The PROTECT trial is expected to enroll about 300 patients ages 8-17 with recent onset T1D at 90 centers worldwide.

Novo Nordisk paused three clinical trials of concizumab over safety issues. The trials are evaluating the drug for hemophilia A and B. No more patients will be enrolled in the trial and current treatment “will cease” while they determine the risks and plans for the trials. Concizumab is a monoclonal antibody against Tissue Factor Pathway Inhibitor (TFPI).

Two of the trials were the EXPLORER 7 and EXPLORER 8 Phase III trials. The other was the Phase II EXPLORER 5 trial. The company indicates the decision was based on non-fatal thrombotic events in three patients enrolled in the Phase III program. The company and an independent Data Monitoring Committee are evaluating the data to determine if the problems are linked to the drug.

AstraZeneca reported that high-level data analysis from its Phase III CASPIAN trial demonstrated that Imfinzi (durvalumab) in combination with standard-of-care (SoC) chemotherapies confirmed a clinically meaningful and sustained overall survival (OS) benefit in patients with extensive-stage small cell lung cancer (ES-SCLC) treated in the first-line setting.

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Back in June 2019, the CASPIAN trial hit one primary endpoint, showing a statistically significant and clinically meaningful improvement in OS compared to SoC alone during a planned interim analysis. A second experimental arm evaluated tremelimumab, an anti-CTLA-4 monoclonal antibody with Imfinzi and SoC, however, and failed to meet the primary endpoint of statistically significant improvement in OS.

Imfinzi is a checkpoint inhibitor. Tremelimumab is an experimental drug that targets cytotoxic T-lymphocyte-associated protein 4 (TCLA-4). It blocks the activity of CTLA-4, helping with T-cell activation, which primes the immune system to respond to cancer. It is being studied in combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and neck cancer and liver cancer.

Arcutis Biotherapeutics presented data from its Phase IIb trial of its topical roflumilast cream (ARQ-151) in patients with chronic plaque psoriasis. ARQ-151 is a topical cream formulation containing roflumilast, a PDE4 inhibitor that is being developed for plaque psoriasis, including intertriginous psoriasis, and atopical dermatitis.

Rhythm’s setmelanotide for Alstrom syndrome received Orphan Drug Designation from the FDA. The drug is being evaluated in a Phase III trial in patients with Alstrom and Bardet-Biedl syndromes. Alstrom is an ultra-rare genetic disorder that results in insatiable hunger and severe obesity. Bardet-Biedl syndrome is also a genetic disorder whose principal characteristic is obesity, retinitis pigmentosa, polydactyly, hypogonadism, and kidney failure. Setmelanotide is a potent MC4R agonist. MC4R is part of the biological pathway that regulates energy expenditure and appetite.

Biohaven Pharma received Fast Track designation from the FDA for its verdiperstat for multiple system atrophy (MSA). MSA is a rare, rapidly progressive, fatal neurodegenerative disease. Verdiperstat is a myeloperoxidase (MPO) inhibitor.

Elivex Therapeutics announced positive final safety and efficacy data from its Phase Ib trial of off-the-shelf Allocetra for severe sepsis. The trial compared clinical data on 10 patients admitted to intensive care with sepsis who were given Allocetra-OTS to 37 patients who were matched controls who received only standard-of-care treatment. Allocetra is an immunotherapy that works to avert cytokine storms and restore safe immune balance without suppressing the immune system.

IVERIC bio decided to delay the initiation of enrollment of patients in the second pivotal trial for Zimura (avacincaptad pegol) for geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). Zimura is a novel complement C5 inhibitor. The delay is related to the COVID-19 pandemic.

Mateon Therapeutics is deploying its OT-101, its Phase III clinical asset as a broad-spectrum anti-cancer drug, into trials against the COVID-19 coronavirus. Currently it is running in-vitro antiviral testing, where it appears to be effective in killing the virus. This work is largely preclinical, but the drug has had successful Phase II trials in pancreatic cancer, melanoma, and colorectal cancers, and in high-grade gliomas, so the drug’s safety profile is known.

The U.S. National Institutes of Health (NIH) announced that a Phase II clinical trial of AstraZeneca and Merck & Co.’s selumetinib in neurofibromatosis type 1 (NF1) shrank inoperable tumors. NF1 is a genetic disorder that can affect multiple body systems. These patients are also at increased risk of developing benign tumors of the nervous system, especially neurofibromas (nerve tumors) and optic pathway gliomas, tumors that form along the optic pathway. Other tumors and forms of cancer are also more common in NF1 patients. The trial was run by researchers in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), part of the NIH. Selumetinib is a MEK 1 and 2 inhibitor designed to inhibit the MEK enzyme in the RAS/MAPK pathway. This pathway is a cell-signaling pathway associated with cancer cell growth and proliferation in a variety of different tumor types.

Genentech, a Roche company, announced it is working with the FDA to launch a Phase III trial with the Biomedical Advanced Research and Development Authority (BARDA) to evaluate Actemra (tocilizumab) plus standard of care (SoC) in hospitalized adults with severe COVID-19 pneumonia compared to placebo plus SoC. The trial is expected to begin enrollment in early April with about 330 patients globally, including the U.S. Actemra was the first humanized interleukin-6 (IL-6) receptor antagonist approved for patients with rheumatoid arthritis and is approved for adults with giant cell arteritis (GCA), active polyarticular juvenile idiopathic arthritis (PJIA) or active systemic juvenile idiopathic arthritis (SJIA).

Pfizer announced positive data from two Phase III trials, one in moderate to severe atopic dermatitis and the other in pneumococcal disease. For the pneumococcal disease, the company announced topline results from a Phase III trial of its 20-valent pneumococcal conjugate vaccine candidate in adults who had not previously been vaccinated against pneumococcal disease. The trial hit the primary immunogenicity objectives of non-inferiority for the 20 serotypes. For the Phase III JADE COMPARE trial of abrocitinib, an oral once-daily Janus kinase 1 (JAK1) inhibitor, the trial met its co-primary efficacy endpoint at Week 12, showing it was statistically superior with both doses of the drug compared to placebo.

Bellerophon Therapeutics received FDA emergency expanded access for its inhaled nitric oxide (iNO) delivery system, INOpulse, to be immediately used for COVID-19. NO is a naturally occurring molecule critical to the immune response. In vitro research had demonstrated that NO inhibits the replication of SARS-CoV and improves survival for cells infected with the virus. In a clinical trial of SARS-Co-V, iNO showed improvements in arterial oxygenation, decrease in the need for ventilation support, and improvement in lung infiltrates seen on chest radiography.

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