Monoclonal Antibodies: Are There Shortages and Why

Monoclonal Antibodies: Are There Shortages and Why

As Americans fight to secure life-saving treatments for COVID-19, an important question is being asked: Are there shortages of monoclonal antibodies (mAbs) in certain areas, and, if there are shortages, why are the shortages taking place?

In September, UncoverDC wrote that the Biden administration suddenly decided to reclaim the distribution of mABS.

At the time, the decision was both concerning and bewildering because the distributor, AmerisourceBergen, seemed to be both competent and well-equipped to handle the distribution. As the article describes, AmerisourceBergen did what it was designed and built to do. Even a cursory look at the AmerisourceBergen website shows a finely-tuned operation with a history of using its real-time distribution tools to responsively target and deliver treatments where and when they are most needed.

There is evidence that shortages exist. On Jan. 3, Florida’s Governor, Ron DeSantis, issued a press release asking the Biden administration to “release [its] stronghold on life-saving monoclonal antibodies.” The state’s Surgeon General, Dr. Joseph Lapado, wrote a letter to Department of Health and Human Services Secretary Xavier Becerra on Dec. 28 describing a “dramatic reduction in the number of monoclonal antibodies” that were being allocated to the State of Florida.

Lapado’s letter was sent because Becerra had announced the federal government would be halting the distribution of Regeneron and Eli Lilly mAbs to states “saying the therapies were unlikely to be effective against the Omicron coronavirus variant.” Whether mABS are effective against Omicron or not, Lapado cites NOWCAST data showing that “over 20% of COVID-19 cases in the Southern U.S. are the Delta variant. Based on this estimate, a significant portion of Floridians would benefit from early treatment options now being withheld by the federal government.” According to the DeSantis press release, Lapado’s letter prompted a reversal in the administration’s decision.

There is some evidence that the Regeneron and Eli Lily products have reduced efficacy with the Omicron Variant. And the evidence is beginning to show that the GlaxoSmithKline (GSK) and Vir Biotechnology, Inc. product, Xevudy (Sotrovimab), is, in fact, more effective in treating the Omicron Variant. GSK announced in November:

“Sotrovimab is an FDA EUA authorized investigational single-dose intravenous (IV) infusion SARS-CoV-2 monoclonal antibody. Under the EUA, Sotrovimab can be used for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive test results for COVID-19 and who are at high risk for progression to severe COVID-19, including hospitalization or death.

Regeneron confirmed on Dec. 16 that the “[c]urrently authorized REGEN-COV® (casirivimab and imdevimab) antibodies have diminished potency versus Omicron, but are active against predominant Delta variant.”

Sotrovimab was approved later than the other monoclonals in May of 2021. A revised letter of authorization for its EUA was reissued on Dec. 16, 2021. As of November, there were government contracts for “approximately $1 billion[1] (USD) now in place to purchase Sotrovimab, further expanding access nationwide,” bringing the “total number of doses secured through binding agreements to more than 750,000 globally. And,
“the COMET-ICE Phase III trial showed Sotrovimab reduces hospitalisation and risk of death by 79% in adults with mild-to-moderate COVID-19 who are at high risk of progression to severe disease.”

There is no way to determine or test definitively that Omicron is actually the variant circulating but its “unprecedented degree of efficiency of transmissibility” suggests to scientists and doctors that it is most likely the Omicron variant circulating. Therefore, doctors are being told that “essentially everything that’s being detected is Omicron,” according to Dr. Karen Bloch, the medical director for Vanderbilt’s COVID Infusion Clinic in Tennessee.

In a Dec. 28 interview, Dr. Bloch seems to confirm what the federal government believes about which monoclonal antibodies work on Omicron:

“The variant is so different that these [older] antibodies can’t find a landing place or a connecting area, and so they are not effective. The one that is still effective is a much more conserved area on the spike protein, so it still is able to attach and prevent propagation of infection.

Historically we have been using other two [antibody treatments] preferentially. They are the older ones, they are more established, we had a larger supply of them and then this again has kind of shifted our needs significantly and there has been a shortage.”

Dr. Bloch believes the shortage is because the “surge of Omicron cases has caused a shortage of Sotrovimab, the one monoclonal antibody treatment that’s been preventing Omicron patients from becoming seriously ill. Sotrovimab is the only antibody treatment doctors are giving out right now since the omicron variant is now accounting for more than 90% of COVID cases.”

The shortage issue seems to be more nuanced than people realize, and it isn’t clear whether the information circulating indicates nefarious motives for the shortages. One hypothesis has emerged as probable. The federal government is ill-equipped to be as responsive as is a company like AmerisourceBergen, whose business is to deliver therapeutics in real-time to the locations that most need them.

For example, in an NTD interview on Jan. 12, the Dealmed CEO, Michael Einhorn, states that “the way the products are being distributed right now, relying on the government to determine who gets what, that process can be very lengthy in terms of time.” Dealmed is a medical supplies company involved in the distribution and supply of monoclonal antibodies across southeastern and northeastern regions of the country.

Einhorn reports that infusion centers are reporting “surpluses in certain areas, not enough in other areas,” fueling frustrations when monoclonals are not delivered to critically ill patients. Einhorn believes big government intervention is at the heart of the shortages:

“Government intervention is a main driver in the supply chain issues. [There are] several different layers of problems one on top of the other but the way the products are being distributed right now, relying on the government to determine who gets what and that process can be very lengthy in terms of time and oftentimes you have surpluses in certain areas not enough in other areas.”

Einhorn believes the free market is more responsive to the efficient distribution of these life-saving therapeutics:

“I think many people in the public believe that government intervention often is the solution. We’re seeing it isn’t, and I don’t think that’s the best way to go about an issue like we’re dealing with now with these shortages of these critical therapeutics.”

He explains in a free market, infusion centers would order products according to their needs. However, in this case, since the government is offering the monoclonals for “free” (taxpayers foot the bill), it is just natural human behavior to accept the shipment whether needed or not. That, in turn, creates oversupply in some locations and shortages in others. It is not an accurate and responsive supply chain delivery system. A Jan. 5 letter from members of Congress in Florida to Secretary Becerra confirms Einhorn’s sentiments. Thus, explains Einhorn:

“I think by just by that mismatch, just by that alone, you have product going in places where it shouldn’t, and you have a product that’s needed that isn’t going to where it’s needed. When the government determines the need, what’s going to happen is they’re going to send to that need even though it may or may not be there and so what ends up happening is the supply chain becomes even tighter because you’re by mistake sending products where it’s not needed or where the government thinks it’s needed. Nobody’s going to say ‘No’ to the government.

I find it very difficult to believe that, in a mere year, a governmental agency in a different state can figure out the dynamics of a local, regional health care system.” 

Wednesday’s Dark to Light podcast featured Dr. Christina Parks, who has a Ph.D. in Cellular and Molecular Biology, among other credentials. Tracy Beanz mentioned that she had seen information circulating that some states are allocating monoclonals based on color. Tracy reasoned that the allocation was maybe because communities of color are at higher risk of severe disease or illness. Parks confirmed some of those vulnerabilities in her discussion—a podcast well worth the listen.

New York state, however, is espousing prioritization of mAbs treatment based on color because of “systemic and social inequities.” There is no available data, however, that suggests the policy is itself causing shortages of therapeutics.

Of note is the fact that Congressman Chip Roy (TX-21) has written multiple letters to HHS about shortages of mAbs. His Sept. 13 letter questioning the distribution changes was never answered. Roy followed up on Nov. 16, adding language indicating there may be “racial discrimination” concerning the distribution of the therapeutics. Roy posits that HHS is “rationing based on” the color of one’s skin. Becerra missed the deadline of Nov. 29 to reply. Roy wrote another letter on Dec. 29. The December letter focused on questions about shortages due to the circulation of Omicron. Roy emphasized the lack of transparency despite multiple inquiries on the subject. Roy’s questions are not without merit, given the life-saving nature of the treatment:

“My recurring inquiries, as discussed in multiple letters and reiterated over a bicameral congressional briefing led by your Department on Sept. 17, 2021, have been focused on a few main questions: 1) Is there, or has there ever been a shortage of any monoclonal antibody treatments in the U.S.? If so, which treatments? 2) Is there an expected shortage of any monoclonal antibody treatment in the U.S.; and If so, which treatments? 3) What is the U.S.’s manufacturing capacity for monoclonal antibody treatments?”

The Biden administration stepped up its orders of the Regeneron mAbs in September when it reclaimed distribution. Regeneron announced that it would manufacture 1.4 million additional doses. The company will supply the doses through 2022. The United States pays Regeneron $2,100 per dose, which the government provides to patients at no cost. Regeneron will be paid $2.94 billion for the additional doses, according to its Sept. 14 press release.

The administration of mAbs for treatment is time-sensitive and reserved for high-risk individuals. Administration of mAbs must occur within 10 days of symptom onset. GlaxoSmithKline and VIR, partners in the manufacture of Sotrovimab,​ announced on Jan. 11 that “600,000 additional doses” will be supplied during Q1 2022, bringing the total to 1.7 million globally.

This story from UncoverDC provides a comprehensive discussion from Dr. McCulllough of the many early treatment options that help avoid severe disease and/or death from the more pathogenic variants of COVID-19, like the Delta variant. Dr. McCullough is one of the pioneers who has been effectively treating COVID-19 for months now.

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