Formerly favored Covid drugs ineffective on Omicron could put millions at risk
And without a government program like Operation Warp Speed to develop second-generation vaccines and treatments, at-risk patients could be at risk of developing severe cases of Covid and flooding hospitals as the US healthcare system is already under strain, thanks to an influx of patients with various respiratory illnesses, including influenza and RSV.
“Just because we’ve moved out of the emergency phase of the pandemic doesn’t mean Covid is over or no longer dangerous,” said Leana Wen, professor of public health at George Washington University. and former Baltimore Health Commissioner. “There are millions of Americans who are vulnerable to serious illnesses.”
The FDA withdrew approvals for four antibody treatments in 2022 as Omicron and its countless subvariants wiped out their effectiveness. The treatments were for adult and pediatric patients with mild to moderate Covid who were considered to be at risk of developing serious illness and ending up in hospital.
Although antiviral pills are plentiful and remain an option for some people with weakened immune systems, they won’t work for everyone – Pfizer’s Paxlovid interacts with many widely prescribed medications.
Monoclonal antibodies – which have been made by companies like Regeneron, Eli Lilly and Vir – are lab-created molecules designed to block the entry of a virus into human cells. But they must bind to the virus’ spike protein to neutralize it, and the many mutations of the coronavirus since its emergence in 2019 have gradually rendered available products ineffective.
“It’s a bit risky to develop this,” said Arturo Casadevall of the Johns Hopkins Bloomberg School of Public Health, noting how quickly some Covid variants surfaced before rapidly receding.
A massive spending bill lawmakers passed before Christmas left out the administration’s $9 billion demand for more money to fight the pandemic, meaning there are fewer dollars to be distributed to meet emerging Covid needs.
“Due to congressional inaction and a lack of funding, HHS does not have the resources to fund the development of new treatments, and we could end up with a very limited medicine cabinet at a time when we need more tools to fight Covid-19,” a department spokesperson told POLITICO, adding that HHS is working with providers and other groups “to ensure Americans can enjoy of all available treatment options”.
The Biden administration has strongly promoted oral antiviral regimens like Paxlovid, which debuted a year ago and marked a turning point in managing the virus for most Americans.
Immunocompromised people — who are born with immunosuppressive conditions or acquire them after an organ transplant or by taking certain medications — may also not develop sufficient immune responses after vaccination, making treatment options like antibody therapies an essential tool for them.
A CDC alert issued Dec. 20 to clinicians and public health professionals warned of the lack of viable monoclonal antibody treatments — including the reduced effectiveness of a prophylactic antibody, Evusheld — and the availability of options antivirals that to date have had poor uptake. The agency urged providers to consult the National Institutes of Health’s Covid treatment guidelines for how to potentially handle drug interactions with Paxlovid, such as temporary breaks or dose reductions.
Remdesivir, an antiviral given intravenously, is another treatment option for immunocompromised people, but it requires infusions over three days in the hospital or on an outpatient basis. HHS urges states to support its health departments and systems in setting up infusion clinics to expand access to remdesivir, especially on an outpatient basis, and is working with manufacturer Gilead to expand the types of providers eligible to purchase medication.
Covid convalescent plasma remains an option for immunocompromised people who contract the virus, but its availability is scattered across the country, Casadevall said. The treatment has pros and cons, he said – it’s less likely to be overcome by one variant and can adapt to different strains, but it’s difficult to administer and requires blood typing for the recipient .
Still, Casadevall said, the main issue is educational because its use has changed since the early days of the pandemic, when treatments were scarce. Some hospital systems, like Hopkins, use it regularly, while some doctors don’t know that plasma is still an option, he said.
The FDA has authorized the emergency use of convalescent plasma containing high levels of Covid antibodies for immunocompromised patients. But the NIH has remained neutral on treating this population, which, according to Janet Handal, president of the Transplant Recipients and Immunocompromised Patient Advocacy Group, has led some hospitals to be reluctant to administer it.
NIH spokeswoman Renate Myles pointed to the agency’s treatment guidelines for Covid, which are being developed by a panel of experts.
The Covid convalescent plasma recommendations, last updated on December 1, say there is “insufficient evidence” to recommend or against using the treatment in immunocompromised patients, while noting that some panel members would use plasma to treat an immunocompromised person “with significant symptoms attributable to COVID-19 and showing signs of activity [viral] replication and has an inadequate response to available therapies.
“In these cases, clinicians should aim for a high titer [Covid convalescent plasma] from a vaccinated donor who has recently recovered from Covid-19 likely caused by a … variant similar to the variant causing the patient’s illness,” the guidelines state.
Casadevall, who leads the Covid-19 Convalescent Plasma Project, says the NIH’s position on plasma is inconsistent with its previous monoclonal antibody recommendations, which were made without clinical efficacy data, since Covid antibodies are the component active in both therapies. He led a petition earlier this month — signed by several doctors, including past and current presidents of the Infectious Diseases Society of America — asking the NIH to change its recommendations.
Handal’s group also asked the NIH and the White House to convene a meeting with scientists on the matter.
“Not having a dialogue about it infuriates us,” Handal said. “People are dying while people are going through this bureaucratic dance.”
The FDA and the European Medicines Agency hosted a virtual workshop this month to bring together doctors, industry and regulators to discuss support for new monoclonal antibody treatments.
“The FDA is committed to working with industry sponsors to accelerate the development of new drugs to address unmet needs, such as the need for new preventative therapies for immunocompromised patients who are unlikely to meet the vaccination,” an agency spokesperson said.
In the meantime, Regeneron spokeswoman Tammy Allen said the company, whose use of the antibody cocktail was limited in January, is committed to evaluating antibody treatment options as the coronavirus is evolving.
“We believe that monoclonal antibodies have played an important role in the COVID-19 pandemic to date and may still play in the future, especially in immunocompromised people,” Allen said.
Vir, which has partnered with GSK on sotrovimab, continues to study whether the treatment might work against emerging variants and is also evaluating next-generation antibodies and small molecule therapies, spokeswoman Carly Scaduto said.
Still, drug companies may be more inclined — both financially and practically — to pursue development of better antiviral pills that pose fewer drug interactions and are easier to administer, said clinical pharmacy specialist Jason Gallagher. infectious diseases at Temple University Hospital. Antivirals are also more resilient to an ever-changing virus, he added.
“There’s a lot more money in Paxlovid than there is in any monoclonal antibody treatment,” Gallagher said, and it may take incentives for drugmakers to encourage their development. . “They won’t make anyone really rich.”