Candidates: Janssen COVID-19 Vaccine Candidate (formerly JNJ-78436735 and Ad26.COV2.S) and two backup candidates

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: 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:

● ANTIVIRAL
● VAX
● ANTIBODY
● RNA

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