“We’re preparing for 2021 today”: An update on the Therapeutics Accelerator

We’re very excited about the number of partners who have joined the effort over the past two months. The Therapeutics Accelerator was originally launched with $125 million in support from Wellcome, Mastercard, and the Bill & Melinda Gates Foundation. As of today, more than $250 million has been committed, and donors now include the Chan Zuckerberg Initiative, the United Kingdom’s Department for International Development, the Michael & Susan Dell Foundation, Avast, Alwaleed Philanthropies, EQT, and the artist and philanthropist, Madonna.

We’re starting to realize the vision for an international, coordinated effort. Many of the donors, including Avast and Alwaleed Philanthropies, who announced their commitments this week, are participating in the Therapeutics Accelerator as part of their larger efforts to participate in the COVID-19 response.

We’re also rapidly mobilizing the Therapeutics Accelerator’s resources towards developing and scaling up treatments.

We have funded five research efforts to date, two of which we covered here.

We are also funding a new clinical trial starting this week. That trial will evaluate the safety and efficacy of hydroxychloroquine and the antibiotic azithromycin as treatments for COVID-19. Azithromycin is a generic antibiotic that is highly effective in treating a wide array of bacterial infections, and researchers believe that it could be effective in preventing pneumonia associated with severe COVID-19 infection. It is also easy to make and inexpensive, so it could be quickly scaled as a treatment for COVID-19 associated pneumonia in low- and middle-income countries.

Researchers at the University of Washington are now enrolling outpatients with COVID-19 for a randomized controlled trial looking at the effectiveness of two drug regimens – hydroxychloroquine and hydroxychloroquine with azithromycin. The trial will enroll 630 patients at sites across the country, including Seattle, Boston, New Orleans, New York City, Syracuse, and Chicago.

The study wants people who have tested positive for COVID-19 but are not sick enough to be hospitalized, and it will enroll two categories of participants – high-risk and low-risk. High-risk outpatients are those over the age of 60 or with an underlying risk factors, such as diabetes, hypertension, obesity, and lung problems. The low-risk group will be outpatients aged 18-59 who don’t suffer from any of those preexisting conditions. Participants will be enrolled into three : hydroxychloroquine, hydroxychloroquine with azithromycin, and a placebo.

The study will measure nasal viral shedding by asking study participants to collect nasal swabs every day for 14 days. The viral shedding pattern will be compared between the different treatments. If a treatment leads to faster clearance of viral shedding, it could theoretically decrease the risk of passing the virus on to others. If another medicine comes along that looks promising, the trial can be adapted to test that, too.

Results of the trial are expected by July and will determine whether hydroxychloroquine plus or minus azithromycin are safe to administer and look promising enough for larger clinical trials.

The concept is based on an understanding of how SARS-CoV-2, the virus that causes COVID-19, interacts with cells in the body. The virus binds to a specific receptor, called ACE2, which shuts off the production of an enzyme that breaks down a protein called angiotensin II. Too much angiotensin II can lead to a variety of outcomes, including high blood pressure, but also lung damage.

We believe there is the possibility that losartan, an angiotensin II receptor blocker, could stop or slow that damage. Researchers at the University of Minnesota will look at outcomes on lung injury, and whether the drug can prevent hospitalization. Losartan has an established safety profile, and it’s easy to manufacture in large quantities. So, we’re interested to see if this could be part of the toolbox available to help address aspects of COVID-19.

The answer is time.

Let’s say the Accelerator effort leads to an effective drug, but that we didn’t invest in any manufacturing capacity beforehand. Then, we’d spend months or longer waiting for those facilities to be readied for production. The world doesn’t have that kind of time to waste when it is facing a disease as deadly and infectious as COVID-19. By forging a partnership with FUJIFILM Diosynth Biotechnologies (FDB), we’re preparing for 2021 today.

The agreement lets us reserve capacity next year for the manufacture of a monoclonal antibody therapeutic candidate that’s identified in clinical trials this year. FDB is a world-class contract development and manufacturing organization (CDMO), and it is equipped with six bioreactors that can rapidly manufacture cell-culture-derived biologics for clinical and commercial use.

Our plan is to have FDB manufacture a biologic that proves safe and effective in early phase clinical trials so that the product will be available for use in a large-scale clinical trial and ultimately available in mass quantities if that trial proves successful. The Therapeutics Accelerator will also ensure that the biologic manufactured by FDB is equitably distributed to low- and middle-income countries (LMICs).

The La Jolla Institute for Immunology is leading this effort. It has established a Coronavirus Immunotherapy Consortium, CovIC, to bring together scientists from around the world to share and evaluate COVID-19 antibody candidates side-by-side using a blinded, multidisciplinary analysis.