By Jaimy Lee
A mix of legacy drug makers and small startups have stepped forward with plans to develop vaccines or treatments that target the infection caused by the novel coronavirus.
COVID-19, which was first detected in December in Wuhan, China, has since sickened nearly 4.6 million people worldwide and killed more than 300,000, as of mid-May.
The Food and Drug Administration has issued two emergency-use authorizations for COVID-19 treatments, including one for hydroxychloroquine sulfate and chloroquine phosphate in March to treat COVID-19 patients and one for Gilead Sciences Inc.’s remdesivir on May 1. No drugs or vaccines have received FDA approval.
In the U.S., many of the publicly traded companies that are initiating development have received funding from two organizations: the Biomedical Advanced Research and Development Authority, or BARDA, which is a division of the Department of Health and Human Services, and the National Institute of Allergy and Infectious Diseases, or NIAID, a division of the National Institutes of Health. Some companies have also received funding from Coalition for Epidemic Preparedness Innovations, or CEPI, a global organization based in Oslo that has provided millions of dollars in funding to vaccine makers. Other companies are funding trials by themselves or through life-sciences-company partnerships.
These are some of the companies developing treatments or vaccines in the U.S. for COVID-19, as of early May. (An earlier version of the article included several adjuvant platform technologies that are used to aid the development process and a privately held company, but they have since been removed to focus on public companies.)
Amgen and Adaptive Biotechnologies
Type: Antibody treatment
Background: The very early-stage collaboration between Amgen Inc. /zigman2/quotes/209157011/composite AMGN +0.73% and Adaptive Biotechnologies Corp. /zigman2/quotes/212846591/composite ADPT +4.22% seeks to discover antibodies that can be used to prevent or treat COVID-19. Financial terms of the exclusive collaboration will be completed “in the coming weeks,” the companies said April 2 . “There may well be more than one generation of antibody therapeutics entering the clinic,” Amgen R&D EVP David Reese told investors on an earnings call.
Also in the works: Amgen will test Otezla as a COVID-19 therapy treating respiratory distress in late-stage patients, with the company saying April 30 that it plans to put the oral psoriasis drug into trials “in the coming weeks.”
Year-to-date stock performance: Amgen’s stock is down 1.9%; Adaptive’s is up 10.3%.
Background: Altimmune Inc. /zigman2/quotes/207059226/composite ALT +14.31% said March 30 it is partnering with University of Alabama at Birmingham to develop a single-dose, intranasal COVID-19 vaccine. They said they plan to put the vaccine candidate into Phase 1 trials in the third quarter. The preclinical company is also developing vaccines for anthrax and the flu.
Year-to-date stock performance: Shares of Altimmune have gone up 60.8%.
BioNTech and Pfizer
Type: mRNA vaccine
Stage: Phase 1/2
Name: BNT162 program
Background: Pfizer Inc. /zigman2/quotes/202877789/composite PFE +0.64% announced March 17 it would help develop and distribute BioNTech SE’s /zigman2/quotes/214419716/composite BNTX -1.68% COVID-19 vaccine candidate, though the deal excludes China. The 360 patients in the U.S. trial had started to receive the first doses of the four vaccine candidates included in the study as of May 5. Dosing in 200 participants in the German trial began April 23. As part of the deal, Pfizer will pay $185 million upfront, with additional possible future milestone payments of up to $563 million. Mikael Dolsten, Pfizer’s chief scientific officer, said during an April 28 earnings call that the companies expect the first round of trial data in May or June, with the vaccine candidate moving into “expanded trials that could allow emergency use or accelerated approval coming in the fall, possibly October.”
BioNTech is also testing the vaccine in collaboration with Shanghai Fosun Pharmaceutical Group Co. Ltd. in China.
Pfizer and BioNTech for several years have said they are working on mRNA-based influenza vaccines.
Year-to-date stock performances: Shares of BioNTech have soared 47.6%; Pfizer’s stock is down 1.7%.
Stage: Phase 2 and Phase 2b/3 clinical trials
Background: CytoDyn Inc. /zigman2/quotes/203536088/delayed CYDY -2.21% , a preclinical biotechnology company based in Vancouver, is testing its experimental drug leronlimab in two types of COVID-19 patients. The investigational therapy hasn’t been approved for any indications; for COVID-19, it is being proposed as a treatment for mild-to-moderate respiratory complications that occur in patients with the disease as well as severely and critically ill patients .
The randomized, double-blind, placebo-controlled study will test the efficacy and safety of leronlimab in 75 patients. CytoDyn had been studying the experimental therapy as a treatment for people with HIV and a form of metastatic breast cancer.
Year-to-date stock performance: CytoDyn’s stock has soared 213.0%.
Stage: Emergency use authorization
Background: Gilead Sciences Inc. /zigman2/quotes/210293917/composite GILD -0.22% is a longtime drugmaker best known for developing the first major cure for hepatitis-C in Sovaldi, a therapy that changed the standard of care for that disease but also kicked off the national debate about drug pricing. The company has experience developing and marketing HIV drugs, including Truvada for pre-exposure prophylaxis (PrEP), its preventive HIV medicine.
It received an emergency-use authorization from the Food and Drug Administration in the U.S. on May 1 based on preliminary results from two clinical trials: one conducted by the NIAID, and one by Gilead. In the NIAID trial, COVID-19 patients taking the drug had a median recovery time of 11 days, compared with 15 days for those patients taking placebo. NIAID director Dr. Anthony Fauci has said the drug is now considered the standard of care; however, other experts have had mixed responses to the data. Dr. Eric Topol, director of the Scripps Research Translational Institute, said he thinks the drug is effective based on the preliminary data that has been made public. “It’s just not that potent,” he said via email.
The drug was also used in two randomized, controlled clinical trials in China. Results from one trial, which was stopped early, found the drug didn’t produce “statistically significant clinical benefits,” according to findings published in The Lancet .
Gilead in late March had to halt individual compassionate use requests for remdesivir as outbreaks worsened in the U.S., having provided the investigational therapy to 1,000 patients. “The system cannot support and process the overwhelming number of applications we have seen with COVID-19,” Gilead CEO Daniel O’Day said March 28.
The company told investors on May 1 it may spend up to $1 billion this year to develop and manufacture remdesivir, and it aims to have 500,000 treatment courses by October and 1 million by the end of 2020.
Gilead’s notable clinical trials:
1. The National Institute of Allergy and Infectious Diseases trial has enrolled patients in a randomized, double-blind, placebo-controlled Phase 3 trial evaluating 1,063 hospitalized patients with COVID-19 at 68 sites worldwide, including at three sites in Singapore and South Korea, according to the NIAID. However, the majority of the study locations are in the U.S. The study began Feb. 21 and is expected to conclude April 1, 2023. Preliminary results from this trial were used to inform the EUA.
2. A Gilead-sponsored randomized, open-label Phase 3 trial is testing remdesivir in 1,600 patients with moderate COVID-19. It previously said it would enroll 600 participants. The trial started enrolling patients in March, with results to come in May. The clinical trial listing states the study is taking place in 13 countries, including Hong Kong, Singapore, South Korea and the U.S.
3. A Gilead-sponsored randomized, open-label Phase 3 trial is evaluating remdesivir in 6,000 patients with severe COVID-19. The drugmaker previously said it planned to include 400 participants in the trial. The trial started enrolling patients in March, and early results based on 397 patients included in the initial phase of the study were used to inform the EUA. The clinical trial listing states the study is taking place in Hong Kong, Singapore, South Korea and the U.S.
Results: The EUA followed two weeks of clinical trial data leaks that sent the company’s stock soaring or tumbling depending on the news. Stat News reported April 16 that University of Chicago Medicine researchers saw “rapid recoveries” in 125 COVID-19 patients remdesivir, though that data isn’t part of the full clinical trial data set. A week later, Stat and the Financial Times reported that a draft of the clinical trial results for remdesivir showed that the drug didn’t speed up improvement in patients in China or prevent them from dying. The summary was reportedly published by accident on the World Health Organization’s (WHO) website and then taken down.
What’s next: The drugmaker plans to donate 1.5 million vials, about 140,000 10-day courses of treatment, of the drug through June. It also said May 5 that it plans to contract with pharmaceutical manufacturers abroad to ensure access to remdesivir outside of the U.S. The Institute for Clinical and Economic Review, a group that assesses the cost-effectiveness of medicines, said Gilead would need to charge $10 for a course of treatment to recoup its costs, but could be priced as high as $4,500 per course of treatment to be considered effective.
Year-to-date stock performance: Shares of Gilead are up 21.2%.
Type: Vaccine, treatment
Name: AS03 adjuvant system for vaccines
Background: GlaxoSmithKline /zigman2/quotes/209463850/composite GSK -0.34% is another leading vaccine maker, having brought to market vaccines for human papillomavirus (HPV) and the seasonal flu, among others. It has announced a string of wide-reaching collaborations during the pandemic, most notably a deal with Sanofi to jointly develop a vaccine candidate. (Sanofi is also working with BARDA on a separate vaccine program.) As part of this agreement, Sanofi’s S-protein COVID-19 antigen will be paired with GlaxoSmithKline’s adjuvant technology; the companies expect to launch clinical trials in the second half of the year. Terms of the agreement are expected to be completed this month.
Also in the works: GSK said Feb. 3 that the CEPI-funded University of Queensland will have access to its vaccine adjuvant platform technology, which is believed to both strengthen the response of a vaccine and limit the amount of vaccine needed per dose. A separate deal with Clover Biopharmaceuticals Inc., a Chinese biotechnology company, which was announced in February, is also using its adjuvant technology in combination with its vaccine candidate, COVID-19 S-Trimer, in preclinical studies. Dr. Thomas Breuer, chief medical officer for GSK Vaccines, is leading work on vaccines and the adjuvant platform.
Separately, GSK and Vir Biotechnology Inc. announced a deal in early April, in which GSK made a $250 million equity investment in Vir as the two companies work together to develop two of Vir’s experimental therapies, VIR-7831 and VIR-7832, expected to go to Phase 2 clinical trials sometime in 2020.
Year-to-date stock performance: Shares of GSK have tumbled 11.3%.
Background: Heat Biologics Inc. /zigman2/quotes/207470740/composite HTBX +12.58% has previously announced that it is developing a vaccine for the novel coronavirus with the University of Miami Miller School of Medicine. It disclosed March 17 in a financial filing that its COVID-19 vaccine candidate had been added to the World Health Organization’s “draft landscape” of 41 candidate vaccines. “We are finalizing completion of the vaccine and plan to commence preclinical testing this quarter,” Heat CEO Jeff Wolf said in an April 29 statement.
The company also recently joined the Alliance for Biosecurity, which may help it “secure government funding to support its rapid development, production, and distribution” of its COVID-19 vaccine, according to Maxim Group analysts.
Year-to-date stock performance: Heat’s stock has gained 14.8%.
Type: DNA-based vaccine
Timeline: Phase 1 clinical trial
Background: Another CEPI grantee (with roughly $17 million in total awards), Inovio Pharmaceuticals Inc. /zigman2/quotes/202993817/composite INO -1.12% is testing its vaccine candidate in a Phase 1 clinical trial at two sites in the U.S.: the Perelman School of Medicine at the University of Pennsylvania and the Center for Pharmaceutical Research in Kansas City, Mo.
Inovio develops immunotherapies and vaccines but hasn’t yet had a product approved for treatment. For INO-4800, preclinical testing was performed between Jan. 23 and Feb. 29. The company began clinical trials in the U.S. with up to 40 participants in April, dosing the first patient on April 6. Inovio said it expects to have the first results from the trial in the fall and to have 1 million doses of the vaccine ready for additional clinical trials or emergency use by the end of the year.
Inovio on March 12 announced a $5 million grant from the Bill & Melinda Gates Foundation to test a delivery device for its vaccine candidate. In late March, Inovio said that Ology Bioservices Inc., a contract development and manufacturing organization, had received a $11.9 million contract from the Department of Defense to support future potential manufacturing of Inovio’s vaccine candidate for military personnel.
Year-to-date stock performance: Shares of Inovio have soared 209.5%.