Candidates: JNJ-78436735 (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.

Status: Johnson & Johnson (J&J) Chief Scientific Officer Paul Stoffels, MD, told Reuters November 17 that the company expects by year end to have recruited all 60,000 patients planned for its ongoing Phase III ENSEMBLE trial (NCT04505722), based on its current pace of recruiting more than 1,000 patients per day. “Efficacy endpoint should be there in the first few weeks or months, January or February, of the new year,” Stoffels said.

Three days earlier, 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 ongoing 60,000-participant, Phase III ENSEMBLE trial (NCT04505722), 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 the 60,000-participant ENSEMBLE study (NCT04505722) 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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