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.”
One such mAbs producer told the TPA recently that while vaccine approval is primarily working on a 9-12 month period, the FDA is taking closer to 12-18 months to approve mAbs treatments.
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.”
Johnny Kampis writes for the Taxpayers Protection Alliance
