FDA Bureaucracy Threatens Essential Covid Treatment

Red tape at the U.S. Food and Drug Administration (FDA) threatens to slow down the development of a treatment in the never-ending battle against the Covid-19 virus.

Monoclonal antibodies (mAbs) treatments, which are antibodies that target certain antigen, proved initially effective against the virus after the FDA granted emergency use authority for five of them. All five can no longer be used due to reduced effectiveness against newer variants of the virus, which shows the need for continuous development of these treatments so they can work against new Covid variants.

Although mAbs is an alternative for immunocompromised patients who cannot take the Covid vaccine or prescription medications due to interaction issues, the FDA bureaucracy is dragging its feet on granting long-term use for mAbs in treating the virus, according to some experts.

Monoclonal antibodies key treatment for immunocompromised and unvaccinated patients

The human body attacks foreign substances through its immune system by making large numbers of antibodies, proteins that circulate through the body until they find and stick to a specific protein called an antigen. After attaching, these antibodies force other parts of the immune system to destroy cells containing the antigen. Researchers can design antibodies that target a certain antigen, such as one found on cancer cells or the Covid virus. They make many copies of that antibody in a lab, and these are known as mAbs.

It is estimated that there are between 7-18 million immunocompromised people in the United States, and these individuals tend to get sicker and suffer more long-term symptoms than others when they get Covid. Treatments with oral antivirals (such as Paxlovid) may have been effective for many Americans in the fight against Covid, but many immunocompromised patients suffered negative reactions when these antivirals interacted with drugs they were already taking.

In addition, universal immunization against Covid is not achievable for the rest of the population. An estimated 20 percent of Americans have not taken a single Covid vaccine dose, and only about 30 percent are getting annual booster shots against the virus (on par with annual flu shot participation).

Crucially, a recent medical study found that treatment with mAbs in Covid outpatients resulted in fewer hospital admissions than no antibody treatment. The results, published on the American College of Chest Physicians (CHEST) website, found that only 4 percent of mAbs-treated patients later required hospitalization versus 7.7 percent of those not treated by mAbs. Those who were hospitalized also saw better outcomes: 5.8 days in the hospital compared to 8.5 days, and requirement of mechanical ventilation of 4.6 percent versus 16.6 percent.

“Real-world data revealed a strong association between receipt of neutralizing monoclonal antibodies and reduced hospitalization and death among Covid-19 outpatients across multiple pandemic phases and provide valuable date to inform scarce resource allocation decisions,” said Dr. Matthew K. Wynia, director of the Center for Bioethics and Humanities at the University of Colorado Anschutz Medical Campus.

FDA says it is working diligently on mAbs approval, critics have a different take

The Taxpayers Protection Alliance (TPA) sent a letter to FDA Commissioner Dr. Robert Califf in June asking about requirements for approval of mAbs. The letter also asked that the administration embrace a more flexible regulatory structure. In a September response, signed as being from Center for Drug Evaluation and Research (CDER) Executive Operations, the author noted that mAbs became less effective as new variants emerged.

“FDA is working closely with sponsors to facilitate development of mAbs that retain activity against currently circulating variants to address immediate unmet needs, and to facilitate development of new products with conserved targets that are less susceptible to changes in SARS-CoV-2,” the letter said.

CDER Executive Operations added that “the Agency will exercise flexibility when appropriate for a development program while ensuring that the relevant legal standards for safety and effectiveness are met.”

There is disagreement about the accuracy of this statement. CDER declined to follow-up to further inquiries, writing on Nov. 8 that it “included the relevant information in our September 27 email.”

Glenn G. Lammi, executive director and vice president of legal studies at the Washington Legal Foundation, told TPA that it is important that healthcare practitioners have access to a broad range of tools in combatting a virus as persistent and evasive as the coronavirus.

“Early in the pandemic, mAbs were found to be quite effective in reducing the severity of Covid-19 symptoms without any serious side effects,” Lammi said. “Because mAbs don’t run the risk of negative interactions with other drugs and don’t require a healthy immune system to be effective, mAbs may be the only preventative and treatment option for some Americans.”

Lammi pointed out that since mAbs become less effective as the coronavirus spike protein mutates, these treatments can only be truly effective long-term options for Covid treatment if the FDA takes a more innovative approach to approval for each new variant.

“FDA has shown flexibility with vaccine alterations once FDA became comfortable with the platform, which it did more rapidly than normal due to the urgency of the Covid-19 situation,” Lammi said. “Monoclonal antibody producers argue that FDA needs to show the same sort of urgency in mAb review, and that the agency should utilize existing data from mAb use during the pandemic toward approval of a general mAb platform and then allow for alterations as viruses mutate and manifest as new variants.”  

Reps. Dan Crenshaw (R-Texas) and Lori Trahan (D-Mass.) sent a letter to Califf in May, requesting information on the FDA’s plan for mAbs approval.

"While the FDA has modernized its process in the past for influenza vaccines and pioneered an unprecedented public-private partnership through the multi-agency Operation Warp Speed for COVID vaccines, we fear it has not provided the same attention to other interventions," they wrote. "Our foremost concern is that new variants are developing faster than current FDA emergency use authorization (EUA) reviews can be completed – all despite the continued innovation to update drugs and biologics for a changing virus."

In a response to the lawmakers, the FDA assured the members that it would weigh the risks of accelerated approval of treatments like mAbs against the benefits to underserved communities.

“We’d like to take FDA at its word, but so far, its refusal to move beyond the square box of ‘how things are done’ makes us wonder just how much FDA is considering the benefits,” Lammi said.

Ike Brannon, president of Capital Policy Analytics, told TPA that FDA accelerated approval of mAbs when they were vitally needed, but now that the initial pandemic is over, and Covid has become endemic, the administration wants to treat mAbs like ordinary drugs, which Brannon describes as impractical.

“The problem seems to be that they haven't come up with a practical way to approve these in a timely manner outside of what they did during the pandemic, and they don't see any urgency to resolve this issue,” Brannon said. “The data indicates that mAbs have been effective treatments, and I think losing this treatment is highly problematic given that Covid is still causing hospitalizations and deaths every day.”

Brannon said that the smaller proportion of potential patients for mAbs treatments might impact how slowly the approval process is taking, “and the fact that some portion of these are unvaccinated probably impacts their decisions as well although I doubt they would admit it.

“I don't think they're getting a ton of political pressure to address the situation and there's certainly no internal pressure to do so,” he continued.

Anthony Lasso, professor and chair of economics at DePaul University, told TPA that the FDA could treat mAbs as a “platform with annual updates based on circulating virus strains and thus not be subject to reproving each year that the proverbial wheel is still round. I’m honestly not sure why they are not viewing what is a relatively mature technology in this way.”

Lasso said he is bullish on mAbs technology moving forward, in its practical uses beyond Covid treatments.

“When we talk about the promise of ‘personalized medicine’ mAbs is front-line what people are thinking,” he said. “There is hope in cancer therapies as well as treatment for many chronic diseases.”