US Adds To Antibody Push With $486m AstraZeneca Deal
AstraZeneca PLC has signed a deal with the US government worth around $486m for development and supply of its investigational long-acting monoclonal antibody therapy for COVID-19.
The therapy, named AZD7442, is just about to enter large-scale trials as both a preventative against SARS-CoV-2 infection, and as a therapy for those already infected.
The move comes after both Eli Lilly and Company and Regeneron Pharmaceuticals, Inc. submitted their monoclonal antibody therapies for Emergency Use Authorization last week, based on encouraging early data – the latter backed by a glowing presidential endorsement after Trump himself was treated with the drug (Also see "Coronavirus Update: Praised By Trump, Regeneron Files Antibody Cocktail For Emergency Use Authorization" - Scrip, 8 Oct, 2020.)
The $486m contract announced on 9 October via the Biomedical Advanced Research and Development Authority (BARDA) and the Department of Defense pays for the development and supply of up to 100,000 doses. The US government has the option to acquire a further 1 million doses in 2021 under a separate agreement.
AZ plans to supply up to 100,000 doses starting towards the end of 2020, presuming it can provide sufficient data to gain an EUA from the US Food and Drug Administration.
The US government's Operation Warp Speed leaders hope to have at least one COVID-19 vaccine approved by this time, however mass immunization programs are not expected to begin until mid-2021.
This means the antibody therapies could provide a valuable extra weapon against the pandemic, although the challenge of scaling up production of the antibodies is likely to limit their impact.
AstraZeneca has said that its monoclonal antibody (mAb) therapy differs to others in being a long-acting antibody (LAAB) combination.
The LAABs have been engineered with the company’s proprietary half-life extension technology to increase the durability of the therapy for six to 12 months following a single administration. The combination of two LAABs is also designed to reduce the risk of resistance developed by the SARS-CoV-2 virus.
The deal with AstraZeneca follows a similar agreement struck with Regeneron in July worth $450m. At first glance, AstraZeneca's deal looks to be more favorable to the company than the Regeneron one. The US government is paying a slightly higher sum for a much smaller supply of therapies - up to 100,000 doses compared to the up to 300,000 for Regeneron's therapy, although this is likely to reflect the promise of a longer lasting protection against infection.
PRESIDENT TRUMP RECEIVED REGENERON'S ANTIBODY THERAPY REGN-COV2 AS PART OF HIS TREATMENT, AND HAS PUSHED FOR THE FDA TO GRANT IT AN EUA.
Of the trials that AstraZeneca is about to begin, one will evaluate AZD7442 to prevent infection for up to 12 months in approximately 5,000 participants. The second trial will evaluate post-exposure prophylaxis and pre-emptive treatment in approximately 1,100 participants.
AstraZeneca is planning further trials to evaluate AZD7442 in approximately 4,000 patients for the treatment of COVID-19.
The agreement builds on initial US government funding of more than $25m to support the early development of AstraZeneca's mAbs.
The company said that the deal was not expected to lift its revenues this year, as the US government funding will only meet the cost of clinical trials and manufacturing. However should its Phase III trials prove successful and AZD7442 become an approved medicine, the company does anticipate setting up supply of the medicine on commercial terms "during and after the current coronavirus pandemic".
The deal has been struck while trials of AstraZeneca and Oxford University's COVID-19 vaccine candidate AZD1222 remain on clinical hold in the US. The trials were halted more than a month ago after one serious adverse event, but after rapid re-starts in other countries, the Operation Warp Speed-backed trial in the US remains paused.
Bharat Biotech To Begin Phase III Trials Of COVID-19 Vaccine Soon
Bharat Biotech will soon begin Phase III randomized, double-blind, placebo-controlled multicenter trials of its COVID-19 vaccine candidate Covaxin, developed in association with the Indian Council of Medical Research (ICMR).
Submitting the trial protocol to India’s regulator, Drugs Controller General of India, the company said it planned to recruit over 28,500 subjects aged 18 years and above for Phase III trials at 19 sites across 10 Indian states.
The subject expert committee (SEC) examining the application has directed Bharat Biotech, which submitted interim data from Phase I and II trials, to provide complete safety and immunogenicity from Phase II trials and provide clarifications on definitions like asymptomatic subjects before granting approval for the third phase.
The company recently announced the use of adjuvant alhydroxiquim-II, licensed from Kansas-based ViroVax LLC, to boost immune response and extend the immunity provided by Covaxin.
The vaccine candidate was well-tolerated in all dose groups and no serious adverse events have been reported so far, with the most common adverse event being pain at the injection site, which resolved transiently, SEC observed. The Phase III clinical trial application proposes a dose of 0.5ml on day 0 and 28, local media reported.
Covaxin was tested in 12 hospitals across the country in the initial stages with volunteers between ages 18 to 55 with no co-morbidities having participated in the trials. Trial sites were spread across Hyderabad, Rohtak, Patna, Kancheepuram, Delhi, Goa, Bhubaneswar and Lucknow among others. (Also see "Coronavirus Update: RECOVERY Finds Kaletra Ineffective, Indian Company Joins Vaccine Race" - Scrip, 30 Jun, 2020.)
Apart from Covaxin, Bharat Biotech is also developing two other COVID-19 vaccines. In May, it signed an exclusive agreement with the Thomas Jefferson University of Philadelphia in the US to develop a candidate using an existing deactivated rabies vaccine as a vehicle for coronavirus proteins.
Prior to this, it had partnered University of Wisconsin–Madison and US-based FluGen Inc. in April to develop a nasal vaccine against SARS-CoV-2, which offers a more convenient, and potentially economical route of administration. (Also see "Bharat, UW-Madison, FluGen Pursue Intranasal COVID-19 Vaccine" - Scrip, 6 Apr, 2020.)
Umifenovir Combination Trial Does Not Meet End-Point
A combination of the antivirals umifenovir and favipiravir for the treatment of hospitalized moderate COVID-19 patients did not result in significant clinical benefit, a study by the Indian company Glenmark Pharmaceuticals Limited has demonstrated.
Glenmark’s FAITH trial with the two drugs did not meet its key endpoints and confirmed that the addition of umifenovir did not show any incremental benefit in clinical outcomes. The study, which enrolled 158 hospitalized patients with moderate disease in India, saw median time to clinical cure improve by only one day (seven as compared with eight) in patients who received the two antivirals, which was not statistically significant and did not justify adding two antiviral agents.
The study’s primary endpoint was time taken from randomization to clinical cure, defined as resolution of baseline clinical signs and symptoms of COVID-19 infection, and an improvement of at least two points on WHO Ordinal Scale for Clinical Improvement, within a time frame of 28 days.
With the addition of umifenovir not yielding any additional benefit over favipiravir monotherapy, Glenmark maintained that the latter along with supportive care remains a “suitable and effective choice” for mild-to-moderate COVID-19 infection.
In June 2020, Glenmark became the first company in India to receive regulatory clearance for manufacturing and marketing favipiravir 200mg tablet (marketed as FabiFlu) as part of an accelerated approval process, in view of the emergency situation of the COVID-19 outbreak in the country. (Also see "Flutter Over Debut Of Glenmark's Favipiravir For COVID-19 In India" - Scrip, 22 Jun, 2020.)
Glenmark, which developed in-house both the active pharmaceutical ingredient and the formulation for the oral antiviral, has since launched the 400mg strength of favipiravir on the market to reduce the pill burden of COVID-19 treatment. (Also see "Coronavirus Update: Favipiravir Scores In Phase III Trial" - Scrip, 24 Jul, 2020.)
There are over half a dozen cut-price favipiravir brands already on the Indian market, including a version from India’s top-ranked drug firm Sun Pharmaceutical Industries Ltd.. Favipiravir originator, Japan's Fujifilm Toyama Chemical Co. Ltd., in August launched its brand Avigan through partner Dr. Reddy's Laboratories Ltd. on the Indian market, highlighting aspects such as the large amount of safety data and superior shelf-life of its product. (Also see "Can Avigan Bite Into Buzzing Indian Favipiravir Market?" - Scrip, 20 Aug, 2020.)
Celltrion Gets Korea Approval For Antibody Trials
Celltrion, Inc. has received an IND approval from South Korea's Ministry of Food and Drug Safety (MFDS) to begin a Phase III clinical trial with CT-P59, its monoclonal antibody candidate for the preventive treatment of COVID-19.
The company will conduct the trial in about 1,000 subjects - both asymptomatic COVID-19 patients and close contacts of COVID-19 patients - mainly in South Korea. The therapy generates antibodies once it is administered, so is expected to prevent infections in high-risk populations such as medical staff and older people.
The company is also progressing a Phase II/III study in patients with mild to moderate symptoms of SARS-CoV-2 infection.
Korea IND Approval For Daewoong
Daewoong Pharmaceutical Company Ltd. has also received IND approval from the MFDS to begin a Phase I clinical trial of DWRX2003 (niclosamide) in the treatment of COVID-19.
The trial will be conducted at Chungnam National University Hospital in healthy individuals and administration will begin later this month. In addition, the company is also speeding up global development of the drug by conducting Phase I studies in India and the Philippines.
Based on the results, it aims to enter Phase II/III multinational trials within this year and to file for conditional approval and emergency use in COVID-19.
DWRX2003 is known to have a mechanism that can inhibit the virus from entering and leaving human cells. The extended action injection formulation uses Daewoong’s proprietary delivery technology to overcome low absorption and possible adverse gastrointestinal effects for the oral form of the drug. With just a single administration, it is expected to maintain effective concentrations.