Monkeypox’s emergency authorization excludes Siga’s drug Tpoxx (1)

The Biden administration’s move to activate the FDA’s emergency powers for monkeypox could quintuple the US vaccine supply, but the latest action doesn’t use that authority to increase treatment options.

HHS Secretary Xavier Becerra has given the Food and Drug Administration the green light to authorize a technique that involves injecting smaller doses of the monkeypox vaccine into the top layer of the skin. Emergency use authorization is limited to vaccines and does not include therapeutics or tests.

“I was surprised to see that it only covers vaccines. Glad to see the statement for vaccines. But there is an urgent need for more accessible therapies,” said Stacy Cline Amin, former lawyer in head of the FDA under the Trump administration who now leads Morrison and Foerster’s FDA regulatory and compliance practice.

“People are really hurting. And it’s really unacceptable that they haven’t been able to access therapies that can relieve their excruciating pain,” she said.

Mary Foote, medical director for the New York City Department of Health and Mental Hygiene, said she was encouraged by recent emergency measures to deal with this outbreak and looks forward to seeing further action by the federal government.

“It is unclear why antiviral treatment could not also be included in this emergency determination,” Foote said Thursday during an Infectious Diseases Society of America press briefing. “Caring for our patients shouldn’t be this difficult. The United States has all the tools we need to ensure that everyone at risk can get the care they need to prevent and treat monkeypox infections. We just need to use these tools. No one should be left behind. It’s not acceptable.

FDA can issue EUAs to bring unapproved uses of products to market faster and with less stringency than full approval during a public health emergency when there are no other alternatives available adequate. An EUA would expand access to treatment for monkeypox by allowing distribution of licensed treatments for the duration of the emergency.

“The concept is that the FDA can use EUAs to authorize off-label uses of products that are approved, but where the use would be inconsistent with their approvals,” Denise Esposito, co-president of Covington & Burling’s global food, drug, and appliance practice group, said.

Siga Technologies Inc.Tpoxx’s smallpox antiviral (tecovirimat) is available to treat monkeypox under an expanded access protocol, which allows access to unapproved drugs outside of a clinical trial. Under expanded access, a clinician must apply for access to this drug from federal authorities, and patients must have a serious or life-threatening illness.

The FDA and Centers for Disease Control and Prevention have said they have cut red tape for expanded access, but complaints persist that it’s a cumbersome process for healthcare providers.

While these steps have definitely made it easier for prescribers, Foote said the expanded access protocol for investigational new drugs remains a labor-intensive process, requiring a lot of time and follow-up visits.

“We’re hearing from many providers, especially in smaller community clinics, who still can’t afford the burden of the IND process, and are giving up on it completely and trying to discharge their patients,” Foote said.

Patients drove more than three hours to the Sexual Health Clinic at Massachusetts General Hospital to access Tpoxx because there were no closer options, said Kevin Ard, clinic director and medical director of the National LGBTQIA. + Fenway Institute Health Education Center. press briefing like Foote.

An EUA “would not leave prescribing to physicians alone, but would announce prescribing guidelines that must be followed to comply with the EUA. For this reason, an EUA might be preferable to CDC clearance to prescribe off-label,” said University of Denver bioethicist Govind Persad.

Neither an EUA nor Expanded Access is considered approval, which is a more rigorous process to pass the FDA’s full safety and efficacy bar.

Clinical tests

An EUA could help reduce regulatory barriers, but it still needs to be coupled with a fully-funded clinical trial that measures the effectiveness of tecovirimat against monkeypox, Persad said.

“While an EUA can be an important step to improve access in the short term, an EUA should not be allowed to lead to a situation where we are not doing clinical trials and therefore never know if the EUA product is actually effective against emergency disease,” he said.

A spokesperson for the Department of Health and Human Services did not say whether the department would expand the monkeypox EUA to include therapeutics, but stressed the importance of clinical trials.

“There are currently no data demonstrating the efficacy of Tpoxx for the treatment of smallpox or monkeypox in humans. Tpoxx has only been tested in healthy human volunteers, free of smallpox or monkeypox infection, to assess safety,” the spokesperson told Bloomberg Law. “Randomized controlled trials are needed to assess the safety and efficacy of Tpoxx in humans with monkeypox infections and to inform appropriate use of the product by healthcare providers.”

Siga could conduct its first human trials as early as next month, the drugmaker told Bloomberg News last week.

Persad also said that despite the benefits of an EUA, it would be undesirable for off-label prescribing to allow low-risk people who do not have monkeypox – and who are unlikely to have been exposed – to obtain limited quantities of Tpoxx. “I don’t know how likely that is, but I can imagine that some low-risk people who are very fearful of monkeypox are seeking a prescription for the prophylactic tecovirimat,” he said.

Emergency flexibilities

Federal laws provide several levers for health authorities to pull when responding to an infectious disease outbreak, with options for determining the extent to which these emergency flexibilities may apply.

First, the Secretary of HHS must issue a public health emergency determination under Section 564 of the Food Drug and Cosmetic Act. Then, the Secretary may issue a statement under Section 564 stating that circumstances exist to warrant the emergency authorization of unapproved medical products or approved medical products for unapproved uses.

The statement can either be categorical in applying only to drugs or diagnostics, or it can apply to all medical countermeasures for a particular outbreak. Once the declaration is in place, the FDA can issue EUAs for specific products under the declaration.

HHS under the Trump administration rolled out product-specific EUAs for Covid-19, but it started with diagnostics before authorizing treatments and vaccines. The difference between the two outbreaks is that initially there were no countermeasures available for Covid-19, while products were available to treat orthopoxes, Amin said.

“There is no reason for EUA authority to be invoked unless it is ready to be used,” Amin said, adding that at the start of Covid, the emergency authority was ready to be used to treat the tests, but there were no vaccines or treatments. still online when the product-specific EUA is released.

Amin said she expects to see an EUA decision for diagnostics and therapeutics follow soon after that for vaccines.

“I understand that steps have been taken to facilitate access to therapeutics, but really I think emergency use authorization should also be considered as it could potentially significantly reduce the bureaucracy involved in access. patients to treatments they desperately need,” she said.