A recent account indicates a successful treatment involving Eli Lilly’s monoclonal antibody treatment for COVID-19, known as bamlanivimab. After receiving an infusion at Mount Sinai hospital in New York City, Just 72 hours after the treatment, 74-year old Al Weiss felt like “Superman.” Recently, not only touted by POTUS as a breakthrough drug targeting COVID-19 but also authorized for emergency use by the U.S. Food and Drug Administration (FDA), the Lilly Therapy, and Regeneron’s investigational product (also authorized under EUA) both show promise for outpatient treatment according to study data. With a major second wave of the COVID-19 pandemic, experts forecasted that explosive demand would greatly beat supply causing shortages. The opposite has occurred due to real-world factors that unfortunately point to a growing chasm between the federal research establishment on the one hand and on the other the clinic itself—where care occurs in the clinics, hospitals, and health systems of America. The research apparatus led by the National Institute of Health (NIH) Foundation’s ACTIV isn’t, unfortunately, focusing nearly enough on low cost, easy to deliver and administer treatments, rather opting for highly complex, expensive, novel therapies. Influenced heavily by the National Institute of Allergy and Infectious Diseases (NIAID), a dual reality emerges. On the one hand, a confluence of forces and public-private collaborations have led to unprecedented drug and vaccine development accomplishments (e.g., vaccines progressed to EUA status in just months). While simultaneously, a lack of pragmatic focus on low-cost, early-stage treatments, arguably, has intensified the adverse outcomes associated with the pandemic. The monoclonal antibody products are a case in point. ACTIV, in partnership with Operation Warp Speed, supported $2.5 billion on this novel class of COVID-19 targeted therapy (involving just a few companies). Although they show promise for outpatient care, many factors render them difficult to deliver and administer an accumulating list of real-world challenges results.
Real World Elements Hindering Monoclonal Antibody Use
As TrialSite reported, brilliant Eli Lilly scientists worked at a historic pace to develop what was called LY-CoV555 in partnership with startup venture AbCellera and the National Institute of Allergy and Infectious Diseases (NIAID). The effort and results associated with this collaboration were notable and should be commended. The pharmaceutical sector has demonstrated the powerful results it’s capable of producing if undue bureaucratic, regulatory-inspired restrictions and stage-gates are lifted or at least relaxed.
The U.S. government supported research via NIAID and paid the pharmaceutical company $3.75 billion for the product ($1,200 per dose). Lilly needed that guarantee as they produced the highly experimental therapy “at-risk” meaning they would lose everything if the treatment failed to achieve EUA status.
Now, the drug showed enough promise, although data was limited, for FDA to issue an EUA. However, only for outpatient care focusing on those patients at risk for disease progression or hospitalization. Government research policy makers and planners failed to take time to consider the true marketplace challenges in delivering and administering such a product under pandemic conditions.
TrialSite recently summarized issues associated with this drug shared by Dr. Paul Sax, Clinical Director, Infectious Disease Clinic and Professor of Medicine Harvard Medical School. Those issues included:
- Limited supply
- Requires intravenous use
- Must be administered within 10 days of symptom onset
- Drug doesn’t’ seem to have potential for hospitalized, severe cases
- Patients actually most contagious between 1 day before and 5 days after onset of symptoms—patient should be treated then
- Majority of infusion centers have sizeable number of immunocompromised patients plus cancer patients—problems of bringing COVID-19 positive patients into this setting
- Majority of infusion centers not optimized for urgent referrals
- Infusion process is timely, complex and costly (think social determinants of health and health equity— millions of Americans have no insurance access; no medical home)
- Emergency departments not optimized for 3-hour treatment procedures
- Bamlanivimab formation “tricky to prepare and not stable for very long”
- Serious side effects possible—see package insert
Inhibiting Factors Trigger Low Demand Despite Record COVID-19 Cases
More evidence now mounts that demand for this class of COVID-19 investigational therapy disappoints. NPR recently reported that although this therapy class, which mimics natural antibodies and targets SARS-CoV-2 received extraordinary attention thanks to the public display of POTUS promotion, the factors highlighted by Dr. Sax serve as a reminder that health products not designed to fit into a seamless delivery model may struggle, despite pandemic conditions.
That the monoclonal antibody therapies targeting COVID-19 aren’t designed for real-world care conditions becomes ever more noticeable. That is, the overall administrative and procedural overhead associated with the delivery of the monoclonal antibody therapies to the patient is more conducive to hospitalization scenarios, yet these drugs aren’t effective in treating patients infected with SARS-CoV-2.
Rather, studies indicate that these therapies may be more effective during early treatment. TrialSite has emphasized the importance of the research establishment, that is, the NIH/NIAID/ACTIV/Operation Warp Speed collaborative, pursuing low-cost, easy-to-administer, repurposed or novel therapies for early treatment. Unfortunately, the monoclonal antibody candidates, although apparently effective, aren’t optimized for widespread early-onset use.
Real-World Experience: MedStar Health
Although health care organizations like MedStar Health set up infusion centers for COVID-19, the logistics of getting COVID-19 infected patients into the hospital isn’t straightforward or simple. Perhaps a national expert on this topic just due to her pragmatic experience, Dr. Princy Kumar coordinates the Washington DC-based bamlanivimab infusion center and recently commented to NPR, “As they [COVID patients] are infectious, they can’t just hail a ride-sharing app and show up at the infusion center.” Dr. Kumar continued, “And many of them are reluctant to put a family member, who has to ride with them in the car, at risk. So that’ what we’ve identified to be our main challenge.”
According to Richard Harris’ NPR piece of the 1.2 million doses procured by the federal government, only from 5% to 20% of product delivered has actually been used, reported Moncef Slaoui, chief advisor to Operation Warp Speed.
More Evidence of Challenges
Most recently, Will Feuer writing for CNBC also emphasized growing factors impacting the actual use of the drugs developed by Lilly and Regeneron. Although there is evidence that they can definitely help patients infected with SARS-CoV-2, the virus behind the COVID-19 pandemic, the CNBC journalist verifies mounting evidence that these drugs are not getting to patients despite record numbers of COVID-19 cases.
Mr. Feuer calls out a number of factors from a shortage of staff that are trained on how to administer the drugs combined with delays in COVID-19 testing inhibit use in the healthcare market.
Moreover, prominent groups such as the Infectious Diseases Society of America have recommended against routine use of Eli Lilly’s monoclonal antibody therapy due to a lack of data. Even the National Institutes of Health (NIH) has recommended against considering the Lilly experimental drug as a standard of care citing insufficient data.
Are Public Research Dollars Optimally Allocated?
The market system, if commandeered by the central government and special interests, can offer perverse incentives and less than adequate results for a majority of the population. Unfortunately, the evolving dynamics associated with the confluence of public-private forces appear to evidence what some critics would call a form of albeit well-intentioned “Crony-Capitalism.” As ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) has been empowered to decide which research firms received federal funds for COVID-19 studies, they are in actuality accorded enormous powers in time of the pandemic.
Thus, Operation Warp Speed has transferred over $12.5 billion in public taxpayer money to just a handful of vaccine and therapy development companies; when counting all of the public money going into ACTIV sponsorship of studies, the figure rises well above that. TrialSite has analyzed the ACTIV leadership, pointing to a lack of sufficient health provider participation in any decision making—from the clinic to the regional health center to the health system. Rather a consortium representing industry, federal agency and premier academic medical centers cordoned off the decision-making powers as to what COVID-19 research gets funded. This left out the voice of the practicing doctor—the pragmatic caregiver on the frontlines, along with associated provider staff, in the pandemic.
TrialSite’s ongoing analysis peers into the nature and amount of taxpayer funds allocation into novel therapies and vaccines versus existing repurposed therapies. After all, the existing therapies approved or accepted in the USA and Europe (remdesivir and dexamethasone) are repurposed. In dozens of other nations, favipiravir, a repurposed antiviral has been approved. Although hydroxychloroquine went out of favor, it’s remerged as a favorite for repurposing in Africa for the ANTICOV study. Another generic drug, Ivermectin, has shown considerable promise, with numerous studies showing efficacy. Imagine if ACTIV would have spent even a fraction of the billions on some of these low-cost generics. With probably a year to go before a majority of the population is vaccinated, rapid looks into low-cost approaches are still warranted.