Candidate: Single-Shot COVID-19 Vaccine (formerly JNJ-78436735, Ad26.COV2.S)

Category: VAX

Type: Adenovirus vector vaccine based on 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. AdVac can be used with Janssen’s PER.C6® technology to develop recombinant vaccines against infectious diseases.

2021 Status: J&J DEFENDS VACCINE AFTER CDC SNUBJohnson & Johnson on December 16 defended its Single shot COVID-19 Vaccine after the U.S. Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices cited rare instances of blot clots in some vaccinated people in unanimously recommending against the Janssen shot, and in favor of two other COVID-19 vaccines, Pfizer/BioNTech’s COMIRNATY and Moderna’s COVID-19 Vaccine (also called mRNA-1273 or SpikeVax).

As of December 16, officials had confirmed 54 cases of Thrombocytopenia Syndrome (TTS), nine of which have been fatal, Isaac See, MD, of CDC’s Vaccine Safety Team, told ACIP.

“We appreciate today’s discussion and look forward to working with the CDC on next steps,” Mathai Mammen MD, PhD, Global Head, Janssen Research & Development, said in a statement. “In addition, we strongly support education and generating awareness of rare events, such as Thrombosis with Thrombocytopenia Syndrome (TTS) and how to effectively manage it.”

In the statement, J&J also insisted that it “remains confident in the overall positive benefit-risk profile of its COVID-19 vaccine.”

According to the CDC, women between ages 30-49 are most affected by the potential for blood clotting, at a rate of about 1 in 100,000 shots.

Positive CHMP Opinion–The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) on December 15 issued a Positive Opinion for use of J&J’s Single Shot COVID-19 Vaccine as a booster for adults aged 18 and older at least two months after primary vaccination with the J&J vaccine, and as a ‘mix and match’ booster following primary vaccination with an approved two-shot mRNA COVID-19 vaccine regimen (heterologous boosting).

The CHMP based its Opinion on data that included results from the Phase III ENSEMBLE 2 study, which found a booster of the Johnson & Johnson COVID-19 vaccine given two months after the primary shot provided 75% protection against symptomatic (moderate to severe) COVID-19 globally, and 94% protection against symptomatic (moderate to severe) COVID-19 in the U.S. The vaccine also showed 100% protection against severe COVID-19, at least 14 days post-booster vaccination.

ADDRESSING OMICRON—J&J emailed a statement to news organizations asserting that it was testing the effectiveness of its COVID-19 vaccine against the Omicron variant (B.1.1.529). “We are closely monitoring newly emerging COVID-19 virus strains with variations in the SARS-CoV-2 spike protein and are already testing the effectiveness of our vaccine against the new and rapidly spreading variant first detected in southern Africa,” J&J stated. “We remain steadfast in the benefit the Johnson & Johnson COVID-19 vaccine will provide to millions around the world.”

FULL CANADIAN APPROVAL—Health Canada on November 24 granted J&J full approval for its single-shot COVID-19 vaccine to prevent COVID-19 in individuals 18 years of age and older—the first major regulatory approval for the shot, according to the company. The regulator based its decision on initial data from the Phase III ENSEMBLE trial (NCT04505722) showing the vaccine was 85% effective in preventing severe disease, and showed protection against COVID-19 related hospitalization and death, beginning 28 days after vaccination.

EU Donation to COVAX—The European Union along with Norway and Iceland (Team Europe) have agreed to donate almost 100 million doses of its COVID-19 vaccine through the COVAX Facility to help protect individuals in lower-income countries, J&J said November 22. The doses are being provided under an agreement signed recently by the government of Belgium (acting on behalf of Team Europe), Gavi, The Vaccine Alliance (GAVI) and J&J. The agreement will enable doses of the company’s vaccine to be shipped directly to COVAX for the benefit of low- and middle-income countries through the remainder of this year and into early 2022.

CDC Endorses BoosterU.S. Centers for Disease Control and Prevention Director Rochelle P. Walensky, MD, MPH, on October 21 endorsed the CDC Advisory Committee on Immunization Practices’ (ACIP) recommendation to allow eligibility for a booster shot of J&J’s Single Shot COVID-19 Vaccine for adults ages 18 and older and who were vaccinated two or more months ago.

FDA AUTHORIZES BOOSTER—The FDA on October 20 amended the Emergency Use Authorization of J&J’s Single Shot COVID-19 Vaccine to allow for a booster dose at least 2 months after completion of the single-dose primary regimen to individuals 18 years of age and older. The FDA based its decision on immune response data in 39 participants from a clinical trial—24 who were 18 through 55 years of age, and 15 who were 65 years of age and older.  The study participants received a booster dose approximately 2 months after their first dose, and the results demonstrated a booster response.

Of approximately 9,000 clinical trial participants who received two doses of the vaccine administered at least two months apart and of these, approximately 2,700 have had at least two months of safety follow-up after the booster dose, the FDA said, adding that Janssen’s safety analyses from the studies had not identified new safety concerns.

2021 Status: FDA Panel Recommends Booster Dose—The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) unanimously voted 19-0 on October 15 to recommend Emergency Use Authorization (EUA) for a booster dose of J&J’s COVID-19 vaccine for adults aged 18 and older at least two months following initial vaccination with the single-shot vaccine.

The committee based its vote on results from the Phase III ENSEMBLE 2 trial (NCT04614948) showing that a booster dose at two months provided 94% protection against symptomatic (moderate to severe/critical) COVID-19 in the U.S., and 100% protection against severe/critical COVID-19, at least 14 days post-booster vaccination. Also submitted were findings from a Phase I/IIa study evaluating a booster dose given six months after the first shot, which show antibody levels increased nine-fold one week after the booster, and continued to climb to 12-fold higher four weeks after the booster, J&J said.

J&J added that in the U.S., it had sufficient supply to support booster doses for those who received the more than 15.1 million doses of the Johnson & Johnson COVID-19 vaccine administered as primary vaccinations.

EUA Amendment Sought for Booster—J&J said October 5 that it has submitted data to the FDA supporting its application to expand the Emergency Use Authorization (EUA) of its Single Shot COVID-19 Vaccine to allow a third “booster” dose of the Johnson & Johnson COVID-19 vaccine in individuals 18 years of age and older. The submission included results from the Phase III ENSEMBLE 2 trial (NCT04614948) showing that a booster of the Johnson & Johnson COVID-19 vaccine given 56 days after the primary dose provided 94% protection against symptomatic (moderate to severe/critical) COVID-19 in the U.S., and 100% protection against severe/critical COVID-19, at least 14 days post-booster vaccination.

FDA Panel to Weigh Booster Dose—The FDA said October 1 that its Vaccines and Related Biological Products Advisory Committee will discuss on October 15 an amendment to the EUA of J&J’s Janssen COVID-19 Vaccine for the administration of a third “booster” dose, in individuals 18 years of age and older.

Booster Shot Yields 94% Protection—Johnson & Johnson said September 21that a second “booster” dose of its Single-Shot COVID-19 Vaccine provided 94% protection against symptomatic (moderate to severe/critical) COVID-19 in the U.S., and 75% globally, when given 56 days after the first dose, according to results from the Phase III ENSEMBLE 2 trial (NCT04614948) announced by the company.

When a booster of the Johnson & Johnson COVID-19 vaccine was given six months after the single shot, antibody levels increased nine-fold one week after the booster and continued to climb to 12-fold higher four weeks after the booster. All increases were irrespective of age, J&J added.

J&J said the ENSEMBLE 2 results were consistent with findings from the Phase III ENSEMBLE trial (NCT04505722) posted September 16 in a preprint on medRxiv. Those findings showed the vaccine to have achieved 75% overall efficacy worldwide, and 74% in the U.S., against severe/critical COVID-19. Also in the U.S., the vaccine showed 89% efficacy against hospitalization, and 83% efficacy against COVID-19-related death.

CDC Shows Lesser Effectiveness vs. Delta—The U.S. Centers for Disease Control and Prevention (CDC) on September 10 published a study showing greater vaccine effectiveness vs. hospitalization due to the Delta variant of SARS-CoV-2 among recipients of Moderna’s COVID-19 vaccine (95%) compared with recipients of Pfizer/BioNTech’s COMIRNATY® (80%) or Johnson & Johnson’s Janssen Single Shot COVID-19 Vaccine (60%). Among 14,636 adults hospitalized with COVID-19–like illness, lab-confirmed SARS-CoV-2 infections were identified among 18.9% (1,316 of 6,960) of unvaccinated and 3.1% (235 of 7,676) of fully vaccinated patients. The median age of hospitalized patients was 65, and patient ages ranged from 48–77 years.

Among 18,231 adults with emergency department (ED) or urgent care (UC) encounters for COVID-19–like illness, lab-confirmed SARS-CoV-2 infections were identified among 28.9% (3,145 of 10,872) of unvaccinated and 7.0% (512 of 7,359) of fully vaccinated patients. Vaccine effectiveness vs ED/UC encounters was 92% among Moderna vaccine recipients, compared with 77% for Pfizer/BioNTech and 65% for J&J.

Booster Increases Antibodies Nine-Fold—Researchers on August 24 submitted study summaries to medRxiv containing interim Phase I/IIa data showing J&J’s COVID-19 vaccine generated a rapid and robust increase in spike-binding antibodies, nine-fold higher than 28 days after the primary single-dose vaccination. Significant increases in binding antibody responses were observed in participants between ages 18 and 55, and in those 65 years and older who received a lower booster dose, the investigators reported.

“With these new data, we also see that a booster dose of the Johnson & Johnson COVID-19 vaccine further increases antibody responses among study participants who had previously received our vaccine,” stated Mathai Mammen, MD, PhD, Global Head, Janssen Research & Development.

Lower Antibody Response vs. Delta—In a preprint posted July 19 on bioRxiv, researchers from New York University Grossman School of Medicine reported findings from blood samples drawn from 10 patients vaccinated with J&J’s COVID-19 vaccine, nine vaccinated with Pfizer/BioNTech’s COVID-19 vaccine BNT162b2, and eight vaccinated with Moderna’s COVID-19 vaccine mRNA-1273.

The researchers reported that vaccination with J&J’s vaccine resulted in IC50 titers against Beta, Delta, Delta plus and Lambda variants that decreased between 5- and 7-fold, resulting in mean neutralizing antibody titers of 33, 30, 41, and 36 against viruses with the Beta, Delta, Delta plus and Lambda variant spikes, respectively, “which according to mathematical modeling, could result in decreased protection against infection.” Titers were decreased by 5.4-fold for Delta plus to 6.7-fold for the Beta variant compared to D614G.

Results from the study also showed results also showed, by comparison, that BNT162b2 sera neutralized virus with the D614G and Alpha spikes, with an average titer of 695 and 626. Compared to D614G, the neutralizing titer against Beta was decreased 6.1-fold and Delta plus was 131 decreased 2.7-fold. mRNA-1273 vaccine showed a 3.3-fold 132 decrease in neutralizing titer for Delta plus and 4.6-fold for Beta.

$2.5B Sales Forecast—Speaking on CNBC July 21, J&J Chief Financial Officer Joseph Wolk shared the company’s forecast that its vaccine will generate $2.5 billion in sales this year. But Wolk acknowledged the company has lowered its production forecast for the vaccine, lowering its projected number of doses in 2021 to between 500 million and 600 million, down from 1 billion as earlier estimated—the aftermath of production problems at the Baltimore plant of manufacturing partner Emergent BioSolutions.

J&J generated $164 million in second-quarter vaccine sales–$51 million in the U.S., the remainder overseas—for a six-month total of $264 million.

Label Warns of Guillain-Barré Cases—J&J on July 12 won FDA approval to amend the prescribing label for its COVID-19 vaccine to to include new information about Guillain-Barré syndrome after 100 cases of Guillain-Barré syndrome were reported in vaccine recipients. Of those cases, 95 required hospitalization, and one person died, the FDA said.

Most of the cases occurred within 42 days after vaccination.

“While the chance of having this occur is very low, Johnson & Johnson has updated its COVID-19 Vaccine Factsheet to include important information about these rare cases and on the signs and symptoms of Guillain-Barré syndrome,” J&J said.

Neutralizing Activity vs. Variants—Janssen researchers reported in a preprint posted July 1 on bioRxiv that the company’s single-shot COVID-19 vaccine demonstrated only a 1.6‐fold reduction in neutralization sensitivity against the Delta variant of SARS-CoV-2 (B.1.617.2, identified in India) in an analysis of blood samples from eight participants in the Phase III ENSEMBLE trial (NCT04505722) that assessed the vaccine against more than a half-dozen other variants. The vaccine performed better against the Beta (B.1.351; South Africa) and Gamma (P.1; Brazil) variants with mutations at positions 417, 484 and 501 in the receptor‐binding domain (RBD), as both variants showed the largest reductions in neutralization sensitivity (3.6‐fold and 3.4‐fold, respectively).

However, in a separate preprint posted on bioRxiv, Dan Barouch, MD, PhD, of Beth Israel Deaconess Medical Center, and colleagues, showed in an analysis of datya from 20 patients that humoral and cellular immune responses generated by the Johnson & Johnson single-shot COVID-19 vaccine lasted through at least eight months, the latest timepoint recorded in the study thus far. Data also showed that T-cell responses—including CD8+ T-cells—persisted over the eight-month timeframe examined.

European Manufacturing Site Approved—The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) said June 25 that it approved an additional manufacturing site for the production of COVID-19 Vaccine Janssen. The site, located in Anagni, Italy, is operated by Catalent Anagni SRL. The site will perform finished product manufacturing, CHMP said.

2 Batches Authorized; Doses Ordered Disposed?—J&J on June 11 confirmed that the FDA authorized two batches of its COVID-19 produced by Emergent BioSolutions at a facility in Baltimore where 15,000 doses had to be discarded in March after a manufacturing snafu. But the company would not comment on a report in The New York Times that the agency also ordered the disposal of 60 million other doses due to concerns of possible contamination. The report was published before the FDA disclosed that “several other batches” of the vaccine produced at the Baltimore plant were unsuitable for use.

FDA Extends Shelf Life—The FDA extended the shelf life for the Johnson & Johnson COVID-19 vaccine from 3 months to 4.5 months, J&J confirmed on June 10. The decision was based on data from ongoing stability assessment studies, which showed that the vaccine was stable at 4.5 months when refrigerated at temperatures of 36–46 degrees F (2 – 8 degrees C).

Shipments suspended—The U.S. Centers for Disease Control and Prevention (CDC) has halted new shipments of the Johnson & Johnson COVID-19 vaccine in order to clear a backlog of unused doses before they expire, federal and state health officials told The Wall Street Journal in a report published June 10. Officials in Maryland, Oklahoma, Arkansas, Michigan, Illinois and other states said they had not been able to order new supplies of J&J doses in recent weeks. About 21.4 million J&J doses have been delivered to states, of which neary half (11.5 million) actually been administered.

Effective Against Variants–Dan Barouch, MD, PhD, director of Beth Israel Deaconess Medical Center’s (BIDMC) Center for Virology and Vaccine Research—who helped develop Johnson & Johnson’s COVID-19 vaccine (Ad26.COV2.S)—and colleagues on June 9 published a study in Nature concluding that the J&J vaccine induced immune responses against the original Wuhain strain of SARS-CoV-2 and all of four viral variants studied—first identified in South Africa (B.1.1351 or beta), the U.K. (B.1.1.7 or alpha), Brazil (P.1 or gamma), and California (CAL.20C or epsilon). The data, reported in GEN, showed that the J&J vaccine offered strong protection against symptomatic COVID-19 in South Africa and Brazil where most sequenced COVID-19 cases were caused by variants.

U.K. APPROVES J&J VACCINE—The U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA) on May 28 granted a Conditional Marketing Authorisation (CMA) authorizing use of J&J’s COVID-19 Vaccine Janssen in people aged 18 and over. J&J’s vaccine is the fourth jab approved for use in the U.K., and the first approved for protection from COVID-19 with a single dose. MHRA cautioned, however, that decisions on whether to use the vaccine in pregnant or breast-feeding women should be made in consultation with a healthcare professional after considering the benefits and risks.

Gavi Buys 200M Doses for COVAX—Gavi, the Vaccine Alliance, said May 21 it signed an advance purchase agreement with Johnson & Johnson to purchase 200 million doses of J&J’s single-dose vaccine against COVID-19 for an undisclosed price. The doses were purchased on behalf of the COVAX Facility, with the goal of them being supplied to COVAX participants this year. Gavi is a co-leader of COVAX, which along with other partners works with governments and manufacturers to ensure COVID-19 vaccines are available worldwide to both high-income and lower-income countries.

India Manfacturing Agreement— Biological E will manufacture both J&J’s COVID-19 vaccine, and a COVID-19 vaccine of its own, Mahima Datla, Managing Director & CEO of Biological E, said in a text message to Reuters, after it reported that the Indian company had been looking to contract-manufacture about 600 million doses of the J&J vaccine annually. Dalta declined to give a timeframe or other details.

FDA, CDC Lift Pause–U.S. states have resumed inoculating patients with Johnson & Johnson’s Janssen COVID-19 Vaccine, after the FDA and U.S. Centers for Disease Control and Prevention (CDC) on April 23 lifted their recommended pause in administering the one-dose vaccine, despite confirming 15 cases of what they termed rare and severe blood clots—three of them fatal.

“We have concluded that the known and potential benefits of the Janssen COVID-19 Vaccine outweigh its known and potential risks in individuals 18 years of age and older,” Acting FDA Commissioner Janet Woodcock, MD, said in a statement. “We are confident that this vaccine continues to meet our standards for safety, effectiveness and quality.”

The FDA and CDC followed the advice of the CDC’s Advisory Committee on Immunization Practices (ACIP), which two hours earlier voted 10-4, with one abstention, to recommend lifting of the pause, based on a similar risk-benefit finding. That finding came despite the FDA and CDC confirming that the number of cases of rare and severe blood clots and accompanying low platelet counts had more than doubled from the six that were disclosed when the agencies called for the pause on April 13.

The FDA and CDC have confirmed 15 cases of thrombosis-thrombocytopenia syndrome (TTS) occurring in patients who had been treated with the J&J vaccine. TTS combines thrombosis involving the cerebral venous sinuses (CVST) and other sites in the body, including but not limited to the large blood vessels of the abdomen and the veins of the legs, along with thrombocytopenia or low blood platelet counts. All 15 cases occurred in women between the ages of 18 and 59, with a median age of 37 years. The 15 cases are among 7.89 million recipients of the vaccine nationwide.

Oregon Death 2 Weeks after Vaccination—An Oregon woman in her 50s died from a rare but serious blood clot developed within two weeks of receiving the Janssen COVID-19 Vaccine, the state’s health agency and the U.S. Centers for Disease Control and Prevention (CDC) said April 22. The blood clot occurred with a low quantity of platelets, the Oregon Health Authority (OHA) said.

OHA said it was notified of the potential adverse event on April 20, two days after the CDC was informed about the death through its Vaccine Adverse Event Reporting System (VAERS).

The Oregon woman was inoculated with the vaccine before the CDC and FDA directed state health agencies to pause administration of the vaccine on April 13. The state agency is not releasing additional information on exactly when the woman was vaccinated or where in Oregon she lived, citing state privacy laws.

Researchers conducting the Phase III ENSEMBLE trial (NCT04505722) published data April 22 in The New England Journal of Medicine that a single dose of the Janssen COVID-19 Vaccine protected against symptomatic COVID-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death.

The vaccine showed efficacy against severe–critical COVID-19 of 76.7% for onset at ≥14 days and 85.4% for onset at ≥28 days. Against moderate-to-severe/critical COVID-19, the vaccine showed 66.9% efficacy against the virus with onset at least 14 days after administration, and 66.1% with onset at least 28 days after administration.

Among the 86 of 91 South African patients with the 20H/501Y.V2 variant, vaccine efficacy was 52.0% against moderate to severe–critical COVID-19 with onset at least 14 days, and 64.0% at least 28 days after administration. Efficacy against severe–critical COVID-19 was 73.1% with onset after 14 days and 81.7% after 28 days.

J&J Rebuffed on Clot Study Request: Johnson & Johnson privately contacted Pfizer and Moderna requesting they conduct a joint study about the risk of blood clots from their COVID-19 vaccines, then address public concerns about safety with a single voice, only to be rebuffed by the rivals, The Wall Street Journal reported April 16, citing unnamed sources.

One of the two companies rebuffing J&J was concerned that the safety of their vaccines would be tarnished through association—though a fourth COVID-19 vaccine developer, AstraZeneca, agreed to join with J&J, the Journal reported.

No CDC Decision–The U.S. Centers for Disease Control and Prevention (CDC)’s Advisory Committee on Immunization Practices (ACIP) on April 14 maintained the pause on administration of J&J’s Janssen COVID-19 Vaccine Candidate pending additional information, saying it planned to reconvene in 7 to 10 days to continue reviewing cases of rare blood clots in patients inoculated with the vaccine, and assess their potential significance. The FDA has also begun investigating those cases, and will review the CDC’s analysis, the agencies said in a joint statement a day earlier.

FDA, CDC URGE PAUSE, CITING ‘RARE’ BLOOD CLOTS–The FDA and CDC on April 13 recommended that U.S. states pause their administration of Janssen COVID-19 Vaccine Candidate while they review six reported cases—one of them fatal—in which patients developed what the agencies termed rare and severe blood clots after receiving the vaccine, out of 7 million Americans who received the vaccine. The CDC’s Advisory Committee on Immunization Practices (ACIP) planned an April 14 meeting to review the cases and assess their potential significance. The FDA also planned to investigate those cases, and will review the CDC’s analysis, the agencies said in a joint statement.

“Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” the agencies said, in a statement by Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research and Anne Schuchat, MD Principal Deputy Director of the CDC and a retired rear admiral with the U.S. Public Health Service. The FDA’s Acting Commissioner Janet Woodcock, MD, later said she excpected the pause to only last “a matter of days.”

In the six cases being reviewed by the FDA and CDC, a cerebral venous sinus thrombosis (CVST) was seen in combination with low levels of blood platelets. All six cases occurred among women between ages 18-48, with the symptoms occurring 6 to 13 days after vaccination.

J&J issued its own statement acknowledging it was “aware that thromboembolic events including those with thrombocytopenia have been reported with COVID-19 vaccines.” The company added: “At present, no clear causal relationship has been established between these rare events and the Janssen COVID-19 vaccine.”

It was not known if the six cases include any of the cases that on April 7 led to a pause in the “Vaccines for All” mass vaccination event at Dick’s Sporting Goods Park in Commerce City, CO, hosted with the state of Colorado. Eleven patients experienced adverse reactions to the Janssen COVID-19 Vaccine Candidate. Two of the 11 were transported to nearby hospitals “out of an abundance of caution” after medical staffers concluded they required additional observation, Centura said in a statement.

Johnson & Johnson confirmed in a March 31 statement that a batch of drug substance for its COVID-19 vaccine “did not meet quality standards at contractor Emergent Biosolutions, a site not yet authorized to manufacture drug substance for our COVID-19 vaccine.” As a result, the batch never advanced to the filling and finishing stages of manufacturing, J&J said.

“The issue was identified and addressed with Emergent and shared with the [FDA],” J&J said. “We continue to expect to deliver our COVID-19 vaccine at a rate of more than one billion doses by the end of 2021.”

The plant also produces COVID-19 Vaccines AstraZeneca, which at the time was not emergency-authorized or approved in the U.S.  J&J’s statement came after The New York Times reported that workers at Emergent’s Baltimore plant accidentally conflated the ingredients of the J&J and AstraZenca vaccines weeks earlier, contaminating up to 15 million doses of the vaccine and forcing a delay in FDA authorization of the plant’s production lines.

Catalent said in a March 23 tweet that the FDA had granted emergency use authorization for an expansion of its Bloomington, IN, site in order to produce and ship “millions of doses” of Johnson & Johnson’s COVID-19 vaccine. Those millions are expected to help enable J&J to meet its target of delivering 20 million doses of the one-shot vaccine, Bloomberg reported, citing an unnamed source. As of March 22, only 4.25 million J&J doses had been delivered, and of those, according to the CDC, 2.4 million had been administered.

EU Authorizes Vaccine—The European Commission on March 11 granted a conditional marketing authorization to a fourth COVID-19 vaccine, J&J’s Janssen COVID-19 Vaccine Candidate, based on a a positive scientific recommendation by the European Medicines Agency (EMA). The Janssen vaccine will be given in one dose to adults aged 18 years and older for preventing COVID-19. Janssen will be able to deliver 200 million of its vaccine to the EU starting in the second quarter, the EU said, with member states able to purchase an additional 200 million doses.

Paul Stoffels, MD, vice chairman of the executive committee and CSO at J&J, told Reuters his company expects to produce up to 3 billion doses of the vaccine next year.

Canada Authorizes Vaccine—Health Canada on March 4 authorized J&J’s COVID-19 vaccine in people over 18 years of age—the first single-dose COVID-19 vaccine to be authorized in Canada. The agency is requiring J&J to continue providing information on the safety, efficacy, and quality of the vaccine to ensure the benefits of the vaccine continue to be demonstrated through market use.

The federal government will spend $100 million to enable Johnson & Johnson to double, to 200 million doses, production of its Janssen COVID-19 vaccine, Andy Slavitt, senior advisor to President Joe Biden for COVID-19 response, said March 3. Those doses are now expected to be produced by May.

Merck to Support Manufacturing—Merck & Co. agreed March 2 to use its U.S. facilities to produce drug substance, formulate, and fill vials of the Janssen COVID-19 Vaccine as part of an up to $268.8 million funding commitment from the Biomedical Advanced Research and Development Authority (BARDA). Merck said it will use the funding to adapt and make available a number of its existing manufacturing facilities to produce COVID-19 vaccines and medicines. President Joe Biden announced the Merck-J&J arrangement, which comes in addition to Merck’s planned investment in its global vaccines manufacturing network, part of more than $20 billion in planned capital investments from 2020-2024.

Biden said the agreement will ensure that all adult Americans can access a COVID-19 vaccine by May 2021.

FDA GRANTS EUA—The FDA on February 27 granted Johnson & Johnson an emergency use authorization (EUA) for its Janssen COVID-19 Vaccine Candidate, a day after all 22 members of the agency’s Vaccines and Related Biologic Products Advisory Committee (VRBPAC) unanimously recommended emergency authorization of the J&J vaccine. On February 24, the FDA’s staff recommended agency approval of the Janssen COVID-19 Vaccine Candidate in a briefing document released two days in advance of VRBPAC’s meeting.

The first four million doses of its Janssen COVID-19 vaccine are expected be distributed across the U.S. the week of March 1, with 20 million set to be delivered by the end of March, and 100 million by the end of June.

“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.”

Johnson & Johnson said February 19 its Janssen-Cilag International unit applied to the World Health Organization for an Emergency Use Listing (EUL) for its single-dose Janssen COVID-19 vaccine candidate. The comply has completed its rolling submission of clinical data, which included interim efficacy and safety results from the nearly 44,000-patient Phase III ENSEMBLE clinical trial (NCT04505722). An EUL is a prerequisite to supplying vaccines to the COVAX Facility, a global mechanism designed to facilitate pooled procurement and distribution of COVID-19 vaccines in 190 participating countries, including 92 lower-income countries.

J&J and Gavi, the Vaccine Alliance, which leads the design and implementation of the COVAX Facility, expect to enter into an Advance Purchase Agreement (APA) that would provide up to 500 million doses of the Janssen vaccine to COVAX through 2022. J&J and GAVI agreed in principle to support the COVIX Facility in December 2020.

J&J Applies for FDA EUA—J&J said February 4 it applied to the FDA seeking Emergency Use Authorization (EUA) for the single-dose COVID-19 vaccine candidate developed by the company’s Janssen Pharmaceutical Cos. The application will be discussed February 26 by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC).

J&J’s single-dose COVID-19 vaccine was 66% effective overall in preventing moderate to severe COVID-19 28 days after vaccination in the ENSEMBLE trial, the company said January 29. J&J acknowledged that the efficacy percentages 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 U.S.

The onset of protection was seen as early as day 14, J&J said. Data was based on 43,783 participants accruing 468 symptomatic cases of COVID-19.

Researchers studying JNJ-78436735 published a study January 13 in The New England Journal of Medicine showing that the vaccine provided an immune response that lasted for at least 71 days in participants aged 18-55 years who were evaluated in a Phase I/IIa trial (NCT04436276).

According to the study, neutralizing-antibody titers against wild-type virus were seen in 90% or more of all participants on day 29 after the first vaccine dose (geometric mean titer [GMT], 224 to 354), and reached 100% by day 57 with a further increase in titers (GMT, 288 to 488), regardless of vaccine dose or age group. Titers remained stable until at least day 71. A second dose provided an increase in the titer by a factor of 2.6 to 2.9 (GMT, 827 to 1,266).

Data on durability of immune responses in trial participants aged over 65 years will be available in late January and longer-term follow-up to one year is planned, J&J said.

2020 Status: Enrollment cut to 40,000—Moncef Slaoui, MD, chief adviser of Operation Warp Speed, told reporters on a December 9 conference call that Janssen cut the planned enrollment of participants for its Phase III ENSEMBLE trial (NCT04505722) evaluating JNJ-78436735 from 60,000 to 40,000 participants: “We have already recruited more than 38,000 subjects in the study,” Slaoui said.

The uptick in COVID-19 cases nationwide will enable Janssen researchers to reach conclusions based on a smaller study population, STAT reported, citing an unnamed source. Interim data is expected by the end of January 2021, with an emergency use application (EUA) to be submitted in February.

On November 14, J&J said that it will commit about $604 million while the Biomedical Advanced Research and Development Authority (BARDA) will commit approximately $454 million toward the Phase III ENSEMBLE trial, under an expansion of their partnership. BARDA’s funds come from federal contract OTA No. HHSO100201700018C.

Brazil’s health agency Anvisa has agreed to resume Johnson & Johnson (J&J)’s Brazilian portion of the ENSEMBLE study that it temporarily paused on October 12. The Brazilian portion is s being conducted in 11 states, and is expected to involve up to 7,560 people over the age of 18. At the time of the disruption, Anvisa said when the trial was paused, 12 volunteers in Brazil, all from Rio de Janeiro, had either received a dose of the vaccine or a placebo.

J&J said October 23 it was preparing to resume the U.S. portion of ENSEMBLE—as well as all other clinical trials of the vaccine candidate sponsored by J&J’s Janssen Pharmaceutical Cos.—citing a patient’s “unexplained illness.” According to The Washington Post, which cited two unnamed sources, a male volunteer in his twenties had a cerebral hemorrhage and transverse sinus venous thrombosis following a stroke.

J&J said the trial’s independent Data Safety Monitoring Board (DSMB) recommended that the company resume recruitment of patients after it found no evidence that the vaccine led to the “serious medical event” experienced by the patient.

“Based on the information gathered to date and the input of independent experts, the Company has found no evidence that the vaccine candidate caused the event,” J&J said in a statement. At Johnson & Johnson, there is no greater priority than the health and safety of the people we serve every day around the world. Our primary goal is to ensure the safety, well-being and privacy of the participants and all those involved in our trials.”

The company has offered no details about the participant’s illness, but did say it is in talks with regulators outside the U.S. to resume the trial.

On October 8, J&J said the European Commission had approved an Advance Purchase Agreement through which J&J’s Janssen Pharmaceutical Cos. will supply 200 million doses of JNJ-78436735 to EU member states upon approval or authorization from regulators. The EU member states have the option to secure up to 200 million additional doses.

On September 30, J&J said it plans to set aside up to 500 million vaccine doses for lower income countries beginning “mid next year.” J&J made the commitment under the “Communiqué on Expanded Global Access,” which it signed with 15 other drug, vaccine, and diagnostics developers along with Bill and Melinda Gates. The signatories committed to ensuring that all people worldwide have access to the COVID-19 therapeutics and tests being developed by the companies, regardless of their income level.

A week earlier, Janssen launched the Phase III ENSEMBLE trial, designed to assess the safety and effectiveness of the single-dose JNJ-78436735 compared with placebo in up to 60,000 volunteers across three continents.

ENSEMBLE is a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the safety and efficacy of a single vaccine dose versus placebo in up to 60,000 adults ages 18 years old and older, including what J&J said would be “significant” representation from participants over age 60. The trial will include participants both with and without comorbidities associated with an increased risk for progression to severe COVID-19. Paul Stoffels, MD, vice chairman of J&J’s Executive Committee and CSO, said the company aims to deliver a vaccine for emergency use authorization (EUA) in early 2021.

ENSEMBLE’s primary outcome measure is the number of participants with first occurrence of molecularly confirmed moderate to severe/critical COVID-19 with seronegative status up to 2.1 years following injection.  The trial will enroll volunteers at up to nearly 215 clinical research sites in the U.S. and worldwide. The study’s estimated primary completion date is March 10, 2023 –but preliminary data will be available much sooner, a Janssen spokesperson told The Wall Street Journal.

Researchers from Janssen, Beth Israel Deaconess Medical Center (BIDMC), and clincal partners published a study in Nature on September 3 showing that JNJ-78436735, a single immunization of an Ad26 vector encoding a full-length prefusion stabilized S immunogen (S.PP), protected against severe clinical disease after high-dose SARS-CoV-2 challenge in Syrian golden hamsters.

While sham controls showed marked weight loss, severe pneumonia, and partial mortality, vaccinated animals showed minimal weight loss and pneumonia, and no mortality, the researchers reported. Vaccine-elicited binding and neutralizing antibody responses correlated with protection against clinical disease as well as reduced virus replication in the upper and lower respiratory tract.

In August, the European Commission concluded exploratory talks with Janssen to purchase its vaccine candidate against COVID-19. The EU said the eventual contract would allow all of its member states to purchase the vaccine, as well as to donate to lower and middle income countries or re-direct to European Economic Area countries. Once a vaccine has proven to be safe and effective against COVID-19, the Commission said, it would have a contractual framework in place to purchase an initial 200 million doses on behalf of all EU member states, and could further purchase up to an additional 200 million vaccine doses.

The exploratory talks are intended to yield an Advance Purchase Agreement to be financed with the €2.7 billion ($3.2 billion) Emergency Support Instrument, which has funds dedicated to the creation of a portfolio of potential vaccines with different profiles and produced by different companies.

The U.S. Departments of Health and Human Services (HHS) and Defense (DoD) agreed to provide Janssen approximately $1 billion toward manufacturing and delivering of 100 million doses of JNJ-78436735 to government-designated locations nationwide, through a demonstration project disclosed August 5. The vaccine doses could be used in clinical trials, or as part of a COVID-19 vaccination campaign if authorized by the FDA. If the doses are used in a COVID-19 vaccination campaign, the vaccine would be available “at no cost,” though healthcare professionals could charge for the cost of administering the vaccine.

The demonstration project is part of Operation Warp Speed, the federal effort through which President Donald Trump’s administration has committed the nation to delivering 300 million vaccine doses protecting against SARS-CoV-2 by January 2021. Operation Warp Speed funds and coordinates development of vaccines, drugs, and diagnostics across agencies of the departments of Defense and Health and Human Services (HHS)—the latter agency including the FDA, the NIH, the Centers for Disease Control and Prevention (CDC), and the Biomedical Advanced Research and Development Authority (BARDA).

BARDA collaborated with the DoD Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and Army Contracting Command, to provide the funding. The government also can acquire additional doses up to an amount sufficient to vaccinate 300 million people.

J&J said July 30 that its lead COVID-19 vaccine candidate elicited a robust immune response as demonstrated by neutralizing antibodies, successfully preventing subsequent infection and providing complete or near-complete protection in the lungs from the virus in non-human primates (NHPs), according to a preclinical study published in Nature and conducted by Janssen and BIDMC researchers. Of seven vaccine prototypes tested in the study, Ad26.COV2.S elicited the highest levels of neutralizing antibodies to SARS-CoV-2.

Based on the data, J&J said, a Phase I/IIa first-in-human clinical trial (NCT04436276) of Ad26.COV2.S, in healthy volunteers was launched in July—two months earlier than originally planned—in the U.S. and Belgium. That trial has yielded positive interim data showing that the safety profile and immunogenicity after a single vaccination of JNJ-78436735 supported further development of the vaccine, J&J said.

J&J will evaluate both one- and two-dose regimens of JNJ-78436735 in parallel studies. The randomized, double-blind, placebo-controlled Phase I/IIa trial will evaluate the safety, reactogenicity, and immunogenicity of the vaccine in 1,045 healthy adults aged 18 to 55 years, as well as adults aged 65 years and older.

The company added that it was continuing to increase manufacturing capacity and was in “active” discussions with global strategic partners to support worldwide access. J&J has committed to supplying more than 1 billion doses globally through 2021, provided the vaccine is safe and effective.

Emergent BioSolutions on July 6 announced a five-year manufacturing services agreement with Janssen Pharmaceuticals for large-scale drug substance manufacturing of JNJ-78436735. Emergent agreed to provide contract development and manufacturing (CDMO) services to produce drug substance at large scale over five years beginning in 2021, valued at approximately $480 million for the first two years.

For the three years beginning in 2023, Emergent also agreed to provide a flexible capacity deployment model to support annual dose requirements. Emergent will carry out activity at its Baltimore Bayview facility, a designated Center for Innovation in Advanced Development and Manufacturing (CIADM) by HHS, designed for rapid manufacturing of large quantities of vaccines and treatments during public health emergencies.

The manufacturing agreement expands a $135 million agreement announced in April. At that time, Emergent agreed to provide drug substance manufacturing services with its molecule-to-market CDMO offering, supported by investments from J&J, and agreed to reserve certain large-scale manufacturing capacity to pave the way for commercial manufacturing of Janssen’s adenovirus-based COVID-19 vaccine beginning in 2021.

In June, J&J was said to be in advanced talks with the European Commission to reserve or buy upfront doses of its COVID-19 vaccine under development, according to a Reuters report attributed to two unnamed “officials familiar with the talks.” The potential deal would be the first to tap into an emergency fund of more than €2 billion ($2.3 billion) created by the EU’s 27 member nations in order to secure doses from up to six vaccine manufacturers.

Reuters quoted an unnamed “top health official from an EU member state” as saying the deal was “in the pipeline,” adding that an EU spokesman had no comment.

J&J also disclosed it was in talks with the NIH’s National Institutes of Allergy and Infectious Diseases (NIAID) to accelerate the schedule for the vaccine’s Phase III trial, depending on the outcome of the Phase I/IIa study and approval from regulators.

While the capacity of J&J’s Leiden, the Netherlands-based vaccines launch facility is as high as 300 million doses per year, Stoffels said, the company intends to produce between 600 million and 900 million doses of the vaccine by the end of the first quarter of 2021. J&J has committed to supplying more than 1 billion doses globally through 2021, “provided the vaccine is a safe and effective.”

Janssen’s Ad26.COV2.S is one of three COVID-19 vaccine candidates that will be fast-tracked toward pivotal trials starting this summer, John R. Mascola, MD, Director of NIAID’s Dale and Betty Bumpers Vaccine Research Center (VRC), told The Wall Street Journal in June.

On June 3, The New York Times reported that J&J was among developers of five COVID-19 vaccines identified by President Donald Trump’s administration as most likely to produce a vaccine for the virus, citing unnamed “government officials.” According to the report, the five will receive additional government funding, assistance with clinical trials, and financial and logistical support for manufacturing. A formal announcement is expected in coming weeks.

In April, Janssen said it will rely on Catalent’s Biologics business unit to accelerate availability of segregated manufacturing capacity over coming months to facilitate large-scale commercial manufacturing of the lead vaccine candidate at Catalent’s facility in Bloomington, IN, thorugh a collaboration whose value was not disclosed. Catalent said it plans to hire approximately 300 additional employees at Bloomington for the program starting in July 2020 to meet operational readiness and 24×7 manufacturing schedules by January 2021.

J&J executives told analysts on the company’s quarterly conference call April 14 the company intends to produce between 600 million and 900 million doses of the vaccine by the end of the first quarter of 2021, ramping up to 1 billion doses each year.

In March, J&J said it expected to start Phase I human trials by September for its lead COVID-19 vaccine candidate, and had expanded its vaccine R&D and clinical testing partnership between Janssen and BARDA that is valued at over $1 billion. BARDA has committed more than $456.2 million toward supporting JNJ-78436735, from development through licensure—about half the combined $1 billion-plus committed by BARDA and J&J to development of the vaccine.

J&J said it aims to have clinical data available by year’s end on the safety and efficacy of its lead COVID-19 vaccine candidate, an accelerated development and testing timeframe it said would allow vaccine availability for emergency use in early 2021. The company anticipates it can have the first batches of a COVID-19 vaccine available for FDA emergency use authorization in early 2021.

J&J has committed to bringing an “affordable” vaccine to the public on a not-for-profit basis for emergency pandemic use.

COVID-19: 300 Candidates and Counting

To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:

FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.

DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data

KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.

TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.

GEN has also tagged the most common treatment types:


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