Johnson & Johnson on Saturday became the third developer of a COVID-19 vaccine to be granted an emergency use authorization (EUA) by the FDA, allowing patients to be dosed with the company’s Janssen COVID-19 vaccine candidate—more than two months after the agency granted the first two.

The first four million doses of its Janssen COVID-19 vaccine are expected be distributed across the United States this week, with 100 million doses set to be delivered by the end of June. Unlike Pfizer and BioNTech’s BNT162b2, which received an EUA on December 11, and Moderna’s  mRNA-1273, which was authorized for emergency use a week later, J&J’s vaccine requires only a single dose.

“This milestone follows a year of incredible work by our dedicated teams and unprecedented collaboration with health leaders around the world—all of whom shared a goal of bringing a single-shot vaccine to the public,” Alex Gorsky, J&J’s chairman and CEO, said in a company statement. “We will do everything we can to help bring this pandemic to an end, in the United States and throughout the world.”

In a separate FDA statement, acting FDA Commissioner Janet Woodcock, MD, said: “The authorization of this vaccine expands the availability of vaccines, the best medical prevention method for COVID-19, to help us in the fight against this pandemic, which has claimed over half a million lives in the United States.

“The FDA, through our open and transparent scientific review process, has now authorized three COVID-19 vaccines with the urgency called for during this pandemic, using the agency’s rigorous standards for safety, effectiveness, and manufacturing quality needed to support emergency use authorization,” Woodcock said.

“At least six months”

Answering a GEN question during a briefing with reporters Saturday night, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, offered an approximate timeframe for how long the agency expects developers of emergency authorized vaccines to continue collecting safety and efficacy data before pursuing a full approval or licensure.

“I think in general for vaccines, we’d like to see at least six months of safety follow-up on the population, because that helps us make sure that we’ve captured the kinds of adverse events in a systematic manner that we’d like to,” Marks said.

The FDA would also like at least six months of additional follow-up on efficacy, though some sponsors may have clearly demonstrated efficacy by the time they pursue a biologics license application (BLA), and all sponsors are addressed individually by the agency on what it expects to see in their BLAs, Marks said.

“If they come in for licensure, we may ask them to continue these studies, because we’d like to have longer-term safety data,” he added.

J&J’s vaccine is indicated for the prevention of COVID-19 in individuals 18 years of age and older, as Moderna’s mRNA-based COVID-19 vaccine (mRNA-1273) is indicated, rather than 16 and older as BNT162b2 is indicated.

The J&J vaccine is a recombinant vector vaccine that uses a human adenovirus to express the SARS-CoV-2 spike protein in cells. The vaccine, formerly called JNJ-78436735, emerged from vaccine constructs created and tested by J&J with Beth Israel Deaconess Medical Center (BIDMC), part of Harvard Medical School, using Janssen’s Advac® and PER.C6® vaccine technology platforms, designed for accelerated vaccine development.

AdVac is based on the development and production of adenovirus vectors (gene carriers), and can be used together with Janssen’s PER.C6 technology to develop recombinant vaccines against life-threatening infectious diseases.

In addition to a single dose, another advantage to J&J’s vaccine is that it can be shipped and stored at refrigerator temperatures of 2° C to 8° C (36° F to 46° F), same as the Moderna vaccine, rather than -70º C as with BNT162b2—though on February 19, Pfizer and BioNTech said they submitted new data to the FDA showing the stability of their COVID-19 vaccine when stored at -25° C to -15° C (-13° F to 5° F), temperatures commonly found in pharmaceutical freezers and refrigerators.

20 million+ doses

“Assuming necessary regulatory approvals relating to our manufacturing processes, our plan is to begin shipping immediately upon emergency use authorization, and deliver enough single-doses by the end of March to enable the vaccination of more than 20 million Americans,” Richard Nettles, MD, vice president of U.S. Medical Affairs, Janssen Infectious Diseases and Vaccines, said in testimony February 23 to the Subcommittee on Oversight and Investigations of the U.S. House of Representatives Committee on Energy and Commerce.

J&J’s vaccine has been forecast to generate anywhere from $2.4 billion in sales (Morningstar) to approximately $4.7 billion (AllianceBernstein’s Sanford C. Bernstein unit). According to GEN’s Top 7 Best Selling COVID-19 Vaccines and Drugs of 2020, the top COVID-19 therapeutic by sales was Gilead Sciences’ Veklury® (remdesivir), which generated $2.811 billion last year.

The FDA set the stage for granting J&J an EUA starting on Wednesday, when staff scientists issued a positive assessment of mRNA-1273 in a briefing document that was prepared for the agency’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC).

The FDA scientists reviewed data submitted by J&J from the nearly 44,000-patient Phase III ENSEMBLE trial (NCT04505722), which the company announced January 29. The briefing document highlighted safety and efficacy data submitted by J&J in support of the EUA application it filed earlier this month showing the vaccine to be 66.9% effective in preventing moderate to severe COVID-19 14 days after vaccination, and 66.1% 28 days after vaccination. 

By comparison, Moderna’s final analysis of Phase III data showed its vaccine to be 94.1% effective while Pfizer/BioNTech’s BNT162b2 was shown in its Phase III trial to have achieved 95% effectiveness.

J&J has acknowledged that the efficacy varied depending where the vaccine was administered, with a low of 57% in South Africa, where a variant strain of SARS-CoV-2 from the from the B.1.351 lineage accounted nearly all cases 28 days post-vaccination. Percentages stood at 66% in Latin America and 72% in the United States. However, according to J&J, the vaccine has shown 85% efficacy in preventing severe forms of the virus across all regions studied.

Data submitted to the FDA came from a post hoc analysis of all COVID-19 related hospitalizations among ENSEMBLE participants starting 14 days after vaccination, including non-centrally confirmed cases, two hospitalizations were reported among people receiving the vaccine, none of which were reported after 28 days—compared with 29 in the placebo group, with 16 cases after 28 days.

ENSEMBLE enrolled 43,783 participants in an ongoing randomized, placebo-controlled study being conducted in South Africa, certain countries in South America, Mexico, and the United States. The participants—21,895 of which received the vaccine while the other 21,888 received saline placebo—were all followed for a median of eight weeks after vaccination.

No vaccine-related deaths

As of February 5, J&J told the FDA, there were seven COVID-19 related deaths in the study in the placebo group, but no COVID-19 related deaths in the vaccine group. The J&J vaccine was shown to have a favorable safety profile, with the most common adverse reactions being injection site pain (48.6%), headache (38.9%), fatigue (38.2%), and myalgia (33.2%). These adverse reactions were predominately mild and moderate, with 0.7% and 1.8% of local and systemic solicited adverse reactions, respectively, reported as grade 3.

Among the strains of SARS-CoV-2 studied in the ENSEMBLE trial, 96.4% of sequenced cases in the United States were of the Wuhan-H1 variant D614G, while 94.5% of sequenced cases in South Africa were of the 20H/501Y.V2 variant (B.1.351), and 69.4% of sequenced cases in Brazil showed a variant of the P.2 lineage, with the remaining 30.6% Wuhan-H1 variant D614G.

No cases of the U.K. variant B.1.1.7 or Brazilian variant P1 were seen as of February 12, the FDA reported.

“FDA has reviewed the CMC [chemistry, manufacturing, and control] data submitted to date for this vaccine and has determined that the CMC information is consistent with the recommendations set forth in FDA’s guidance Emergency Use Authorization for Vaccines to Prevent COVID-19 (October 2020). As such, FDA has determined that the Sponsor has provided adequate information to ensure the vaccine’s quality and consistency for authorization of the product under an EUA,” the briefing document concluded.

The 22-member advisory committee unanimously recommended agency approval of the Janssen COVID-19 vaccine. That compares with the 20-0-1 vote recommending approval of Moderna’s mRNA-based COVID-19 vaccine (mRNA-1273) on December 17, and the 17-4-1 vote recommending approval of the Pfizer/BioNTech vaccine on December 10.

Through its recommendation, the VRBPAC concluded that the benefits of J&J’s vaccine outweighed its risks for use in individuals 18 years of age and older, based on the totality of scientific evidence available.

Investors responded by sending shares up 1.6% in after-hours trading as of 7:59 p.m. Friday, to an even $161 a share. J&J shares closed Friday at $158.46, down 2.6% from Thursday’s close of $162.76.

Federal agencies have committed up to nearly $1.5 billion toward supporting J&J’s vaccine candidate from development through licensure—an award of more than $456.2 million in February from the Biomedical Advanced Research and Development Authority (BARDA), followed August 5 by approximately $1 billion from HHS and the U.S. Department of Defense (DoD) to support a manufacturing demonstration project including the ability to deliver vaccine doses to government-designated locations nationwide.

“We believe the Johnson & Johnson single-shot COVID-19 vaccine is a critical tool for fighting this global pandemic, particularly as it shows protection across countries with different variants. A vaccine that protects against COVID-19, especially against the most dire outcomes of hospitalization and death, will help ease the burden on people and the strain on health systems worldwide,” stated Paul Stoffels, MD, vice chairman of the executive committee and CSO, at J&J.