Coronavirus Update: Rapid Japan Approval For Remdesivir, Combination With Lilly's Olumiant Is Next Hope
Other Asia R&D Progress
Executive Summary
Plus: Chugai enters into Singapore research alliance, Korean consortium reports vaccine progress.
Japan Issues Emergency Remdesivir Approval
Drug regulatory authorities in Japan on 7 May granted special expedited approval to Gilead Sciences Inc.’s antiviral Veklury (remdesivir) as a treatment for SARS-CoV-2, the virus that causes COVID-19, under an exceptional emergency approval pathway.
The clearance references the 1 May Emergency Use Authorization for the nucleotide analog from the US Food and Drug Administration and is based on clinical data from the US National Institute of Allergy and Infectious Diseases’ global Phase III trial, Gilead’s Phase III SIMPLE trial in patients with severe manifestations of COVID-19, and other available data from Gilead’s compassionate use program, which included patients in Japan.
Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) said the Special Approval for Emergency was granted due to the urgent need to treat critically ill patients in Japan and was accompanied by several conditions. These include patients’ written informed consent prior to administration, implementation of a risk management plan, submission of results from additional clinical studies within nine months at the latest and surveillance/registry of all patients during a designated period.
“The PMDA and MHLW [Ministry of Health, Labour and Welfare] will continue to evaluate its efficacy and safety and disseminate information, while taking necessary actions immediately,” the agency stressed.
Under Article 14-3 of Japan’s Pharmaceuticals and Medical Devices Act, such expedited extraordinary approvals may be granted when: 1) an emergency situation requires an unapproved medical product to be used to prevent damage to public health caused by disease spread; 2) an emergency situation cannot be managed appropriately by any means other than use of the unapproved product; and 3) such a product is legally available in a country with a regulatory system for medical products equivalent to Japan (in this case the US).
Such approvals can be withdrawn where the special conditions above no longer persist or to prevent damage to public health.
The approval of remdesivir - seen as one of the early and quickest hopes in the global fight against the novel coronavirus – came with astonishing speed. The MHLW regarded Veklury to satisfy the conditions after designation in a Cabinet Order on 2 May, after which Gilead submitted an application on 4 May. The PMDA then conducted a review of the available information, approval conditions and labelling and the results were discussed by the ministry’s Pharmaceutical Affairs and Food Sanitation Council on 7 May.
In the US, remdesivir has been authorized only for the treatment of hospitalized patients with suspected or laboratory-confirmed SARS-CoV-2 infection and severe COVID-19. Severe disease is defined as oxygen saturation (SpO2) ≤ 94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation.
Lilly’s Olumiant Added To Remdesivir In Latest NIH Coronavirus Trial
A new trial is to combine Eli Lilly & Co.’s Olumiant (baricitinib) with Gilead’s remdesivir in the hope that together the drugs could help patients with the most severe COVID-19, and even save lives.
The research is the next phase of the Adaptive COVID-19 Treatment Trial (ACTT), the international adaptive trial which provided the large scale, placebo-controlled data which led to the US Food and Drug Administration giving remdesivir emergency use authorization on 2 May.
The ACTT2 trial is being led by the US National Institute of Allergy and Infectious Diseases as part of a consortium of international government funded researchers. (Also see "COVID-19 Phase III Trial Design: Big Ambitions, Little Consistency" - Pink Sheet, 11 May, 2020.)
The study is especially important as data for Gilead’s drug suggests it only has substantial benefits for those with less severe COVID-19. That means researchers are still looking for a treatment or combination of treatments which can help those in a critical condition and save lives.
The placebo-controlled, double blind ACTT2 trial is now enrolling hospitalized adults with COVID-19 in the US, and is expected to enrol more than 1,000 participants.
Patients who have mild symptoms will not be included in the trial, which will focus on those who have lung involvement, including a need for supplemental oxygen, abnormal chest X-rays, or require mechanical ventilation.
Antony Fauci: still looking for drug or drug combination to cut mortality rates
“We now have solid data showing that remdesivir diminishes to a modest degree the time to recovery for people hospitalized with COVID-19,” said NIAID Director Anthony Fauci. “ACTT 2 will examine if adding an anti-inflammatory agent to the remdesivir regimen can provide additional benefit for patients, including improving mortality outcomes.”
The trial is now getting underway in the US, with Europe and Asia to follow shortly, and results are expected in the next two months.
Chugai, Singapore Agency Start Work On Therapeutic Antibody
Chugai Pharmaceutical Co. Ltd. ’s Singapore research center Chugai Pharmabody Research Pte. Ltd. has begun joint research on a potential therapeutic antibody for COVID-19 with Singapore’s Agency for Science, Technology and Research (A*STAR).
The project will focus on an antibody discovered by a team led by Dr Cheng-I Wang at A*STAR’s Singapore Immunology Network. Lead candidates were isolated from a diverse synthetic human antibody library and showed high potency in neutralizing the live SARS-CoV-2 coronavirus, which causes COVID-19 disease.
Chugai Pharmabody will lead optimization of the candidate and apply the Japanese firm’s proprietary engineering technologies to create a clinical candidate. The two partners have already been working together since 2018 on an antibody research project in dengue fever, supported by a grant from the Japan-based Global Health Innovative Technology Fund.
Chugai Pharmabody was established as a wholly-owned subsidiary of Chugai (which is in turn majority-owned by Roche) in January 2012 and conducts research on novel antibody clinical candidates focusing on first-in-class and best-in-class therapies for various targets, using Chugai’s multiple antibody engineering technologies.
Korean Consortium Sees Early Progress With Vaccine
Genexine Inc. has confirmed that GX-19, its prophylactic DNA vaccine candidate for COVID-19, has generated neutralizing antibodies against the SARS-CoV-2 coronavirus in primate studies, suggesting it has potential against the disease.
A consortium of Genexine, Binex Co. Ltd., the International Vaccine Institute, GenNBio as well as the Korea Advanced Institute of Science and Technology and Postech began to develop a vaccine in March and selected GX-19 as the lead candidate through immune response evaluation.
Preclinical studies have confirmed GX-19 induces a neutralizing antibody response as well as a cell immune response. Binex is manufacturing clinical samples at present and the consortium plans to file for an IND to South Korea’s drug ministry in May to start human trials.