As the New York Times and other news outlets reported yesterday, Rudy Giuliani is the latest of the President’s friends and administration members to receive antibody therapeutics. While we wish Mr. Giuliani and all that have received this treatment well, this does of course raise troubling questions of equity of access. We will leave such questions for the media and politicians to debate. But we do think this should be the stimulus for questions that are just as important: WHY are supplies limited, and WHAT can we do about that?
First, let’s revisit where we stand right now.
- Antibodies have a 100+ year track record of success as a strategy to reduce infections and disease in epidemics, and should have been a top priority for development and production.
- In September and October, the first data from clinical trials by Regeneron and Eli Lilly and others demonstrated efficacy with no significant safety concerns.
- In November, both Regeneron’s Casirivimab and Imdevimab and Eli Lilly’s bamlanivimab received EUAs and have are in nationwide distribution (see: Casirivimab / Imdevimab; bamlanivimab, and both the NIH and FDA specifically highlight the use of antibody therapeutics – subject to the physician’s judgement – for early treatment of at-risk individuals.
- The 3rd wave of the epidemic is once again overwhelming our hospitals and healthcare staff – which is of course leading to a surge in deaths and the rate of deaths per hospitalization, as well as incalculable new economic damage and stress.
- Vaccines are rolling out, but our best case scenario for reaching herd immunity is the end of Q2, 2021, and we cannot be sure they will be fully protective of vulnerable population groups.
Given all of this, one would think there would be an urgent call to action to bring the best currently known therapeutic for COVID-19, which has been shown to reduce hospitalizations and deaths, into the battle with as much speed and volume as possible. What we have instead is urgent discussions around equity of access, and setting up lotteries for the lucky few to receive them.
WHY Are Supplies Limited?
Every news article talks about ‘limited supplies’ and none delve into WHY there are limited supplies! As we blogged about on October 27, therapeutics in general, and antibody therapeutics in particular, have suffered from gross underinvestment and lack of focus and urgency from the very earliest days of this epidemic. Dr. Scott Gottleib, former FDA Commissioner for the Trump Administration, put it this way:
From @BARDA shows prioritization of Covid vaccines over therapeutics by feds. Antibody drugs could be a critical bridge to a vaccine; but supply is sharply limited. It’s not too late to surge new manufacturing; improve distribution of drugs to maximize benefit.Dr. Scott Gottlieb, October 27, 2020
Despite this, since then we still have not heard or seen any move by Operation Warp Speed or any part of the government to increase production. As of this date, there has been no announcement to even confirm that the options on the existing manufacturing agreements with Eli Lilly and Regeneron for additional doses have been exercised!
And WHAT Can We Do About That?
It starts, of course, with the obvious. Whatever existing production capacity and agreements we have for manufacture should be activated immediately. But we must not stop there! This is America. We are a country built of people that break barriers and obstacles to make things happen. We have ample funding, the Defense Production Act, and an infrastructure in Operation Warp Speed to accelerate quickly on breakthroughs. All that is lacking is the will – and action!
An important aspect of monoclonal and polyclonal antibodies is their mode of production. Over the last few decades, Biotech and Pharma companies have developed advanced technologies for selecting – or even synthesizing – biological molecules and then reproducing them in “Bioreactors.” This means that once the best monoclonal and polyclonal antibody “cocktails” are tested and proven, they can be manufactured at scale. In the short term, we can produce with existing capacity – which is substantial, with plans for millions of doses per month by Q1 2021. But given the current rates of infection, this will limit use to only high risk population groups. But with focus and action now, the Federal government can play a critical role in 3 areas to change capacity for both the mid and long term.
1. capital investment – or covering the risks of these – to ramp production;
2. coordination of supplies and production with existing facilities – as Operation Warp Speed is doing now for vaccines; and
3. expand manufacturing on a relatively short timeframe using replicate single-use modular platforms or by identifying and bringing online mothballed facilities
Those that wish to join with us in this call, can do so here:
- Of Prometheus, Super Antibodies and Scaling Production
- Duke Margolis Center for Health Policy: COVID-19 Manufacturing for Monoclonal Antibodies.
How Can We Maximize the Benefit of What We Can Produce in the Short Term?
Supplies are limited, and demand is far beyond capacity if used for everyone that could potentially benefit. But there are also some silver linings that we can leverage. We know:
- what population groups generally are at highest risk of severe illness or death;
- how to monitor individuals that do not fall into these groups, but are showing a progression of symptoms that indicate they are at risk for severe disease or death; and
- how and when to treat at risk patients with antibody therapeutics to reduce their risk of hospitalization and death.
All of this is laid out in by in Operation Warp Speed’s Playbook:
So, with a targeted strategy matching antibodies to those who will most benefit, we can maximize the benefit.
We Need a Strategy for Focused Protection with Antibodies
The public health and medical community should set the specifics of enacting this, but it will also take support from our political leaders and the public. We must have supply, knowledge, awareness and action working in concert to match antibody therapeutics to the right patients at the right time: a strategy of Focused Protection.
The details are critical, but, we think this would be a good place for each state to start.
- Demand funding and action from Congress and Operation Warp Speed to increase production and expedite distribution of antibody therapeutics.
- Implement a communications campaign to the public so that people who are in vulnerable population groups are aware that this therapy exists, and that early action is critical to their effectiveness.
- Set up a registry of these people, as well as a self service Web site for proactive people that would like to determine if they are vulnerable, and be able to develop a concrete plan of action for what they should do if they are infected.
- Set up a hotline and brief physicians / clinics / healthcare networks so that they know what to do with patients in their population that are at risk of severe outcomes from COVID-19.
With this action plan at the state and local level, we could start to empower citizens and public health leaders to work together in a smart, focused way to stay safe and re-open our economy more quickly over the first half of 2021.