October 29, 2020. Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced on Wednesday positive, prospective results from an ongoing Phase 2/3 seamless trial in the COVID-19 outpatient setting showing its investigational antibody cocktail, REGN-COV2 significantly reduced viral load and patient medical visits (hospitalizations, telemedicine visits, etc.).
The randomized, double-blind trial is measuring the effect of adding REGN-COV2 to usual standard-of-care, compared to adding placebo to standard-of-care. A descriptive analysis from the first 275 patients was previously reported. Wednesday’s release of data, involving an additional 524 patients, showed the trial met all of the key criteria and objectives for its impact on reducing “viral load” – stopping reproduction and eliminating the virus – as well as the key clinical criteria and objectives to reduce severity of illness, measured by tracking related medically-attended visits, in patients who had laboratory-confirmed COVID-19.
Here are the key take-aways from our POV – with some “plain English” translations.
- Results showed no significant difference in virologic or clinical efficacy between the REGN-COV2 high dose (8 grams) and low dose (2.4 grams). Based on this finding, Regeneron is reviewing potential changes to dosing in the ongoing outpatient clinical trial given the current limited supply of REGN-COV2.
- On the primary endpoint, the average daily change in viral load through day 7 (mean time-weighted average change from baseline) in patients with high viral load (defined as greater than107 copies/mL) was a 0.68 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p<0.0001). There was a 1.08 log greater reduction with REGN-COV2 treatment by day 5, which corresponds to REGN-COV2 patients having, on average, a greater than 10-fold reduction in viral load, compared to placebo.
- In the overall patient group with detectable virus at baseline, the average daily reduction in viral load through day 7 was a 0.36 log10 copies/mL greater reduction with REGN-COV2 compared to placebo (combined dose groups; p=0.0003).
- As in the earlier analysis, patients with higher viral load at baseline and/or no detectable antibodies at baseline (suggesting their bodies had not yet mounted an effective immune response), derived greater benefit from REGN-COV2 therapy.
- At the early stage of COVID-19, reducing the viral load is the single most important and direct measure of efficacy.
- A much smaller dose than initially tested is just as effective. This is great news as it means the supply can go 3.5 times as far and still be just as effective in protecting against severe illness.
- The earlier you administer the treatment, the more effective it is. But it still helps up to 7 days after infection.
- All of these results were compared against placebo (i.e. no drug), so we know that it is actually the drug that works, not just people getting better on their own.
Clinical results in the overall population
- On the key clinical endpoint, treatment with REGN-COV2 reduced COVID-19 related medical visits by 57% through day 29 (2.8% combined dose groups; 6.5% placebo; p=0.024).
- Treatment with REGN-COV2 reduced COVID-19 related medical visits by 72% in patients with one or more risk factor (including being over 50 years of age; body mass index greater than 30; cardiovascular, metabolic, lung, liver or kidney disease; or immunocompromised status) (combined dose groups; nominal p = 0.0065).
- REGN-COV2 was well tolerated in the trial. Serious adverse events were numerically more frequent with placebo than REGN-COV2 treatment (0.8% high dose, 1.6% low dose; 2.3% placebo). Numerically more infusion reactions occurred with the REGN-COV2 high dose compared to placebo (1.5% high dose; 0% low dose; 0.4% placebo).
- For all patients, it reduced progression to severe illness by 57%. That pool incorporates some people who would have just gotten better on their own.
- For people with the highest risk factors, it reduced progression to severe illness by 72%.
- The drug was well tolerated – there were more adverse side affects in the placebo group than those who received the drug.
Where Do We Go From Here?
These results, taken together with similar results from Eli Lilly, and other earlier stage trials for other antibody drugs, have consistently demonstrated both safety and effectiveness. While this was expected given the long history of success with this approach, the proof must always come in the data from real world clinical trials. This should help expedite the Emergency Use Authorization, of course, and it is encouraging that there appears to be a sharp focus on getting these drugs distributed and targeted rapidly to those that need it the most.
But this must bring us back to the central question and problem: antibody drugs and therapeutics have been grossly under-resourced and under-prioritized as a crucial first wave weapon in the war on COVID-19.
All of this adds up to very promising picture for the availability and application of antibody drugs for the immunoprevention use case starting in Q1 2021, if we put focus and funding to ramp up production now. To paraphrase the old maxim: an ounce of prevention is worth a pound of treatment. Especially with COVID-19, where severe disease or death are strongly correlated to age and prexisting conditions, preventing infection in the first place is by far preferable to treating after exposure.
How rapidly that occurs now depends on two things.
- Building awareness and avenues to connect people in vulnerable population groups that have been infected to rapid treatment with antibody-based drugs.
- Ramping up production and distribution to address the prevention use case – not just treatment.
Immunoprevention.org is dedicated to the first problem from a bottom-up approach, building awareness, acceptance and demand for immunoprevention. But we still need the government to move aggressively on production to ensure that the supply can meet the need! With all of this new momentum, let’s hope that this will finally happen. But instead of just hoping, let’s do something!