Clinical Catch-Up: April 13-17

Clinical data

There’s plenty of news related to clinical trials related to COVID-19, but it does seem to be drowning out non-COVID-19-related clinical trials. Here’s a look.

COVID-19-Related Clinical Trials

CytoDyn reported more than 25 patients have received leronlimab under EINDs from the FDA, and the rate of response in mild-to-moderate patients has been very promising with the first five patients treated being removed from oxygen. So far, as of April 10, 12 patients had been treated in the Phase II trial for mild-to-moderate COVID-19, but results are not yet available. The first site was cleared to enroll patients in the Phase IIb/III beginning April 13. The company treated the first patient with leronlimab in its Phase IIb/III trial for severe and critical COVID-19. The company also has 15 patients enrolled in a Phase II trial for mild-to-moderate COVID-19 patients in the U.S. About 30 COVID-19 patients have been treated with leronlimab throughout the country. Leronlimab was originally being developed in combination with HAART for HIV as well as for metastatic triple-negative breast cancer. It is a humanized IgG4 monoclonal antibody that blocks CCR5. The company also announced that, although it had treated the first patient in its Phase II basket trial with leronlimab for 22 solid cancer tumors, enrollment is being delayed because of the pandemic.

Gilead Sciences is running at least five clinical trials for its experimental antiviral drug remdesivir against COVID-19. Readouts for at least one or two of them will occur this month. Meanwhile, more than 1,800 patients have been treated using the drug on an individual compassionate use basis so far. And they published data in the New England Journal of Medicine on 53 of those patients suggesting promising results.

The study of the 53 patients in the U.S., Europe and Canada who required respiratory support showed that about two-thirds benefited from the drug. About half of the patients received mechanical ventilation and four were on a heart-lung by-pass machine. Eight patients were excluded from analysis, one because of a dosing error and seven because there was no information available on how they did.

All the patients received remdesivir for up to 10 days. Over 18 days, 68% showed improvement, with 17 of the 30 patients on ventilators able to be taken off the devices. Almost half of patients were discharged, while 13% died. Mortality was highest in patients receiving ventilation, with 18% dying.

Although not official and largely anecdotal, there are early signs that Gilead Sciences’ experimental antiviral drug, remdesivir, is effective in treating COVID-19. The company has conducted at least five trials, although at least one in China was halted because of lack of patients to enroll.

A report by STAT suggested that a clinical trial at University of Chicago Medicine was demonstrating early recoveries in fever and respiratory symptoms, with nearly all patients discharged in less than a week.”

Although what STAT is hearing out of that clinical trial is raising expectations, numerous market analysts and scientists are urging caution. Gilead is one of those, providing a statement to Reuters, saying “the totality of the data needs to be analyzed in order to draw any conclusions from the trial.”

The University of Chicago Medicine issued a statement saying that “drawing any conclusions at this point is premature and scientifically unsound.”

Bausch Health initiated a clinical trial program in Canada to study Virazole (Ribavirin for Inhalation Solution, USP) in combination with standard of care for adults with respiratory distress from COVID-19. Ribavirin is a synthetic nucleoside that stops viral replication. The trial has been approved by Health Canada and is expected to launch within the next few weeks.

Eli Lilly and Company made a deal with NIAID to study baricitinib as an arm in NIAID’s Adaptive COVID-19 Treatment Trial. It will study the efficacy and safety of the drug for hospitalized patients starting this month in the U.S., with additional sites planned for Europe and Asia. Baricitinib is an oral JAK1/JAK2 inhibitor marketed as Olumiant for moderately to severely active rheumatoid arthritis.

NantKwest and ImmunityBio, sister companies, are pooling resources to move a COVID-19 vaccine and two different treatments into the clinic before the end of the year. ImmunityBio’s vaccine technology demonstrated safety in Phase II trials in cancer and has also been studied in H1N1 flu, HIV and Zika virus. NantKwest’s natural killer cell product haNK will be tested alone and in combination with ImmunityBio’s T-Cell NK cell stimulator, N-803, and in combination with plasma from recovered  COVID-19 patients. They are also hoping to test a stem-cell-based therapy for severe cases, which is designed to control the immune system’s cytokine storm.

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Tissue Regeneration Technologies launched first coronavirus clinical trial using unfocused shockwave therapy (SoftWaves). The technology appears to have several actions, including stem cell activation, inflammation modulation, improvement of blood flow, antimicrobial and antiviral activity, and dislodging, liquefaction and dilution of viscous fluids such as phlegm. The trial is enrolling patients who failed to respond to ventilators and Extracorporeal Membrane Oxygenation (ECMO).

Chloroquine clinical trial in China. Evidence is accumulating that chloroquine and hydroxychloroquine, drugs traditionally used to treat malaria as well as rheumatoid arthritis and lupus, are not effective in treating COVID-19, the disease caused by the novel coronavirus. A study out of China in 150 hospitalized patients conducted at 16 sites showed the medication did not help patients clear the virus better than standard care. It was also significantly more likely to cause serious side effects.

Sinovac Biotech received a go-ahead to conduct a human clinical trial on its vaccine candidate against COVID-19. In animal studies, the vaccine candidate protected animals without antibody-dependent enhancement (ADE). It also appears to neutralize virus strains from different countries. On April 17, the company announced it had started the Phase I trial with the first group of volunteers receiving their first dose.

Vanda Pharmaceuticals and The Feinstein Institutes for Medical Research, the research division of Northwell Health, enrolled the first patient in the ODYSSEY VLY-686-3501 clinical trial for COVID-19. It will test the use of tradipitant for neurogenic inflammation of the lung secondary to SARS-CoV-2 infection. Tradipitant is a neurokinin-1 receptor antagonist licensed by Vanda from Eli Lilly and Company. It is presently under clinical development for gastroparesis, motion sickness and atopic dermatitis.

BioSig Technologies announced that its subsidiary ViralClear Pharmaceuticals is running a Phase II clinical trial at Mayo Clinic to test its Vicromax (merimepodib, MMPD), a broad spectrum antiviral, in COVID-19. The drug targets RNA-dependent polymerases and has shown broad spectrum activity against RNA viruses, with satisfactory safety data form more than 300 patients treated for hepatitis C.

Beyond Air has approval to initiate a clinical trial in the U.S. using its LungFit system to treat COVID-19 patients. It will treat 20 patients between the ages of 22 and 65 hospitalized with COVID-19. LungFit uses nitrous oxide generated from ambient air to deliver precise volumes of NO to the lungs for possible treatment for a range of pulmonary diseases.

CalciMedica partnered with Regions Hospital St. Paul, Minnesota and Henry Ford Hospital in Detroit to test CM4620-IE in a Phase II study for COVID-19. CM4620-IE is a potent and selective small molecule CRAC channel inhibitor that prevents CRAC channel overactivation, which can lead to pulmonary endothelial damage and cytokine storm in the disease. It has shown clinical safety and potential efficacy in hypoxemia secondary to systemic inflammatory response syndrome (SIRS) from acute pancreatitis.

Mesoblast in collaboration with the Cardiothoracic Surgical Trials Network is launching a Phase II/III trial of its allogeneic mesenchymal stem cell product. It will involve 240 COVID-19 patients with ARDS and run at more than 20 U.S. sites.

Non-COVID-19-Related Clinical Trials

Arcturus Therapeutics announced two clinical trials for its ARCT-810 (LUNAR-OTC) for ornithine transcarbamylase (OTC) deficiency. The FDA gave the go-ahead for a Phase Ib trial in patients with OTC deficiency and a Phase I trial in healthy volunteers was approved by the New Zealand Medicines and Medical Devices Safety Authority (Medsafe). OTC is a life-threatening genetic disease causing high blood ammonia levels that can result in seizures, coma and death. ARCT-810 is a first-in-class mRNA therapeutic.

Moderna released promising early data from a Phase I trial of its experimental Zika vaccine this morning, which could possibly set the stage for similar data for the COVID-19 vaccine. Zika virus is transmitted primarily by Aedes mosquitos. Typical symptoms are mild, including fever, rash, conjunctivitis, muscle and joint pain. At worse it can cause microcephaly and congenital abnormalities in the developing fetus and newborns if the mother is infected during pregnancy. It is caused by a form of flavivirus.

The interim Phase I data from the Zika vaccine candidate, mRNA-1893, showed all four cohorts of the study had been dosed, 10 µg, 30 µg, 100 µg, and 250 µg. Neutralizing antibody titers were evaluated on the 10 and 30 µg doses, which were generally well-tolerated with no vaccine-related serious adverse events (SAEs) or adverse events of special interest (AESI). The most common adverse reaction was local pain at the injection site. Patients were given two doses 28 days apart. The second vaccination did not seem to cause changes in the safety profile.

BeiGene announced its Phase III trial of its checkpoint inhibitor tislelizumab in combination with pemetrexed and platinum chemotherapy for first-line treatment of non-squamous non-small cell lung cancer (NSCLC) met its primary endpoint, showing statistically significant improvement in progression-free survival compared to pemetrexed and platinum alone. Tislelizumab is an anti-PD-1 antibody checkpoint inhibitor.

7 Hills Pharma indicated the FDA cleared its IND for 7HP349, a first-in-class, oral integrin activator. The Phase I trial in the fall of 2020. In short, the drug is an immune stimulant, which might have clinical application beyond cancer, such as influenza, COVID-19 and other infectious diseases.

AstraZeneca presented several posters at the AAAAI Virtual Poster Hall. They include four on benralizumab for asthma and moderate blood eosinophilia; for adolescent patients with severe, uncontrolled asthma; for asthma exacerbation severity in women versus men; and lifetime healthcare costs associated with systemic corticosteroid use in adults with persistent asthma. For tezepelumab, they presented the results from the Phase IIb PATHWAY Study in severe, uncontrolled asthma; the development of a sensitive assay to quantitate circulating thymic stromal lymphopoietin (TSLP) levels in blood; and atopic dermatitis biomarker analysis in type 2 innate lymphoid cells.

Guardant Health published a new Phase I/II study led by Memorial Sloan Kettering Cancer Center showing that the Guardant360 liquid biopsy test effectively identified patients with PIK3CA mutations along with other mutations correlated to cancer resistance, particularly in HR+ breast cancer. The study showed 89% concordance between tissue and blood for PIK3CA mutations in a longitudinal analysis of tumor and blood-based circulating tumor DNA in metastatic patients treated with alpelisib plus fulvestrant. The liquid biopsy test also detected significantly more potential resistance alterations compared to tissue biopsy testing.

GenSight Biologics reported the independent Data Safety monitoring Board (DSMB) completed its second planned safety review of the PIONEER Phase I/II trial of GS030, the company’s novel product combining gene therapy and optogenetics for treatment of Retinitis Pigmentosa (RP). The board confirmed there were no safety issues for the second cohort of three subjects and recommended moving forward as planned with changing the protocol.

Kolon TissueGene announced the FDA’s Clinical Hold issued in April 2019 had been lifted and  the company could continue its Phase III clinical trial of TG-C, an allogeneic cell and gene therapy, in knee osteoarthritis (OA). The trial was suspended because of product identity concerns. It expects to reinitiate enrollment later this year.

Autolus Therapeutics received approval of its IND for AUTO1, its lead CAR-T product candidates for acute lymphocytic leukemia (ALL). The trial AUTO1-AL1 will likely proceed quickly, with minimal impact from the COVID-19 pandemic. It is already open in the UK.

Sunovion Pharmaceuticals published results from a four-week pivotal study of SEP-363856 in schizophrenia. SEP-363856 is a TAAR1 agonist with 5-HT1A agonist activity being evaluated for schizophrenia and other psychiatric diseases. The study showed a statistically significant and clinically meaningful improvement in the Positive and Negative Syndrome Scale.

Clinical Trials Affected by COVID-19

ASLAN Pharmaceuticals paused recruitment of new patients in its trial of ASLAN004 in moderate to severe atopic dermatitis due to the pandemic. It does not expect the pause to materially affect projected timelines for data readouts later this year. ASLAN004 is a monoclonal therapy. These studies were being run in Singapore. It has identified several clinical sites in Australia, which it hopes will join the study mid-year.

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