Monkeypox Vaccine: US FDA Eyes Dose-Sparing Strategy For Jynneos
Executive Summary
Switching method of administration from subcutaneous to intradermal would increase by five-fold the number of doses of Bavarian Nordic’s vaccine available to combat the outbreak; an EUA declaration would be needed to make this change, FDA commissioner Robert Califf said.
The US Food and Drug Administration is considering a dose-sparing strategy for Bavarian Nordic A/S’ monkeypox vaccine Jynneos that could increase by five-fold the number of doses available to combat the outbreak.
The proposed strategy would change the method of administration for Jynneos, the only FDA-approved vaccine to prevent monkeypox, from subcutaneous to intradermal administration.
This approach would allow health care providers to use an existing one-dose vial of the vaccine to administer a total of up to five separate doses, FDA commissioner Robert Califf said during a 4 August briefing by Department of Health and Human Services officials.
“Under the proposed approach, a fifth of the current vaccine dose would be administered intradermally,” Califf said. “There are some advantages to intradermal administration, including an improved immune response to the vaccine. It’s important to note that overall safety and efficacy profile will not be sacrificed with this approach.”
The FDA expects to share more information about this dose-sparing approach in the days ahead, he said.
Rapid Growth in Reported Cases
The proposed dosing strategy is aimed at stretching the US government’s current supply of Jynneos as the monkeypox outbreak continues to grow in the country.
More than 6,600 cases of monkeypox have been reported in the US as of 3 August, up from about 4,600 a week earlier.
The government has made more than 1.1 million doses of Jynneos available to states and other jurisdictions and already delivered 602,000 of those doses. In total, the US has secured 6.9 million doses from Bavarian Nordic, with delivery dates for the remaining doses extending into the fall and 2023.
Intradermal administration is widely used with the purified protein derivative skin test for determining if an individual has tuberculosis.
However, the rapid growth in monkeypox cases has been increasingly concerning to public health officials, leading HHS secretary Xavier Becerra formally declare a public health emergency under Section 319 of the Public Health Service Act on 4 August.
“In recent days, it’s become clear to all of us that given the continued spread of the virus we’re at a critical inflection point, dictating the need for additional solutions to address the rise in infection rates,” Califf said.
“The goal has always been to vaccinate as many people as possible, and for our part HHS has been working closely with the manufacturer to accelerate the availability of additional doses as quickly as we possibly can,” he said. “In the meantime, we’ve identified a potential solution that would allow us to significantly increase the number of doses available to administer to help close this gap.”
Califf said he initially worried that intradermal administration might be too difficult to carry out for some health care providers.
However, he noted this approach is widely used with the purified protein derivative (PPD) skin test for determining if an individual has tuberculosis. The PPD test is routinely used in public health clinics and many other settings and administered by many health care workers every day, Califf said.
“It really means basically sticking the needle within the skin and creating a little pocket there into which the vaccine goes,” Califf said. “This is really nothing highly unusual. It’s done in other situations routinely, so we’re very confident about the administration of the dose.”
The FDA told the Pink Sheet there are a number of approved products indicated for intradermal administration, including allergen skin tests such as those used to aid in the diagnosis of tuberculosis infection and a seasonal influenza vaccine.
When asked about the data supporting the intradermal administration for Jynneos, the FDA said that safety and efficacy will not be sacrificed.
The FDA pointed to a peer-reviewed study, published in 2015 in the journal Vaccine, of Jynneos (also known as Imvamune), which is also approved for treating smallpox. “Data from a reasonably sized clinical trial indicates that a fifth of the dose (0.1 mL) given intradermally (ID) on the same schedule (day 1 and 28) produces similar efficacy to subcutaneous (SC), albeit with notably more local redness, swelling, discomfort, but all was manageable,” the agency said.
No EUA Declaration Yet
If the FDA decides to move forward with the intradermal dosing strategy, an emergency use declaration under Section 564 of the Food, Drug and Cosmetic Act would be needed.
Section 564 permits the FDA to authorize the emergency use of an unapproved medical product, or an unapproved use of an approved medical product, for certain emergency circumstances after the HHS secretary has made a declaration of emergency or threat justifying authorization of emergency use. The EUA process has been used extensively for diagnostics, vaccines and treatments to address the COVID-19 pandemic.
When asked whether HHS was issuing a Section 564 EUA declaration in addition to the Section 319 public health emergency declaration, Becerra said a 564 declaration is “another animal and something we have to consider working with FDA and Commissioner Califf, but we will look at everything necessary to do what we must.”
“We’re feeling very good about the intradermal approach and probably within the next few days, short period of time, we’ll make a final decision about it,” Califf said. “But it looks good right now, and at that point a 564 declaration would be needed to make it available because it’s not the standard previous route of administration.”
Califf’s enthusiasm for the intradermal dose-sparing strategy is notable because FDA officials have strongly cautioned against trying to stretch the vaccine supply by giving individuals only one dose of the labeled two-dose series of Jynneos. (Also see "Monkeypox: Bavarian Nordic’s Jynneos Vaccine Should Be Given Only As A Two-Dose Series, US FDA Says" - Pink Sheet, 15 Jul, 2022.)
Tpoxx Needs a Clinical Trial
On the antiviral front, Califf said the agency wants to see a clinical trial conducted on use of SIGA Technologies, Inc.’s Tpoxx (tecovirimant) for treating monkeypox.
Tpoxx currently is approved only for treating smallpox but is being used for monkeypox under an expanded access program. The government has approximately 1.7 million courses of Tpoxx treatment in the Strategic National Stockpile, with roughly 14,000 deployed to date.
Califf noted Tpoxx was approved for smallpox under the “animal rule” but has never been tested in humans with the disease.
“We think it’s going to be effective in monkeypox, but we have no proof of that yet and so it’s critical as we roll it out through expanded access – and make no mistake our goal is to make it available without excess bureaucracy and paperwork - that we collect data because we don’t know about the risk of the drug or how effective it will be.”
“We are planning a clinical trial which we think is essential to lead to its eventual full approval,” Califf said.
The trial will be conducted by the AIDS Clinical Trials Group, a research network that was established to assess the safety and efficacy of antiretrovirals for HIV, federal officials said in a recent New England Journal of Medicine opinion piece. (Also see "Monkeypox: US Gov’t Leaders Say Tpoxx Needs Randomized Control Trial Before Treatment For All" - Pink Sheet, 3 Aug, 2022.)