Pharmaceutical Technology Editors

Gilead announced on Feb. 1, 2021 that it has entered into a collaboration, option, and license agreement with Gritstone Oncology, a US-based clinical-stage biotechnology company, to research and develop a vaccine-based immunotherapy for human immunodeficiency virus (HIV) infection for up to $785 million.

Under the agreement, Gritstone will provide a $30 million upfront payment and a $30 million equity investment and will be eligible to receive up to an additional $725 million if the option is exercised and all milestones are met, Gilead said in a company press release. Gilead will be in charge of conducting a Phase I study for the vaccine and will hold an option to obtain a license to develop and commercialize the vaccine beyond Phase I.

The vaccine will be developed using Gritstone’s proprietary prime-boost vaccine platform, which includes self-amplifying messenger RNA (mRNA) (SAM) and adenoviral vectors, with antigens formulated by Gilead, according to the press release.

“While HIV treatment has advanced dramatically over the past three decades, people living with HIV still face a lifetime of therapy,” said Diana Brainard, MD, senior vice-president, Virology Therapeutic Area, Gilead Sciences, in the press release. “Curing HIV remains the ultimate aspiration for Gilead’s HIV research and development efforts. Gritstone’s vaccine technology has the potential to educate the immune system to specifically recognize and destroy HIV-infected cells by leveraging SAM and adenoviral vectors. This, along with our other partnerships and internal programs, reflects Gilead’s commitment to continuing innovation to discover a cure for HIV and bring about an end to the HIV epidemic.”

“We are excited to be partnering with Gilead, a company that has decades long experience improving care for people living with HIV, to advance a novel immunotherapy using our proprietary platform for the treatment of HIV infection,” said Andrew Allen, MD, PhD, co-founder, president, and CEO of Gritstone, in the press release. “It is well-established that CD8+ T cells are critical for the elimination of virally infected cells, and we have built a highly differentiated vaccine platform that has been shown to generate large numbers of antigen-specific T cells, including CD8+ T cells, even in advanced and immunocompromised cancer patients. On the heels of our recent COVID-19 program initiation in partnership with the NIH, this program adds to our growing infectious disease pipeline supported by collaborations with leading biopharma and renowned institutions.”

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The vaccine will be developed using Gritstone’s proprietary prime-boost vaccine platform, which includes self-amplifying mRNA and adenoviral vectors, with antigens formulated by Gilead.

Gilead and Gritstone Initiate $785 Million HIV Vaccine Collaboration

on Jan. 29, 2021 that it is recommending conditional marketing authorization for AstraZeneca’s COVID-19 vaccine. The recommendation is based on an assessment of quality, safety, and efficacy data by the agency’s human medicine’s committee (CHMP). The AstraZeneca’s vaccine is the third COVID-19 vaccine to receive authorization by EMA.

According to the agency, results from four clinical trials in the United Kingdom, Brazil, and South America, which included 24,000 people, showed the vaccine is safe and effective in people 18 years and older. “The safety of the vaccine has been demonstrated across the four studies. However, the Agency based its calculation of how well the vaccine worked on the results from study COV002 (conducted in the UK) and study COV003 (conducted in Brazil). The other two studies had fewer than 6 COVID-19 cases in each, which was not enough to measure the preventive effect of the vaccine. In addition, as the vaccine is to be given as two standard doses, and the second dose should be given between 4 and 12 weeks after the first, the Agency concentrated on results involving people who received this standard regimen,” EMA stated in a 

Despite the fact that the majority of study participants were between 18 and 55 years old, the agency stated that while there were not enough results regarding people aged 55 and older, EMA’s experts believe the vaccine can be used in older adults based on the immune response seen in the age group and experience with other vaccines.

“With this third positive opinion, we have further expanded the arsenal of vaccines available to EU and EEA member states to combat the pandemic and protect their citizens,” said Emer Cooke, Executive Director of EMA, in a 

. “As in previous cases, the CHMP has rigorously evaluated this vaccine, and the scientific basis of our work underpins our firm commitment to safeguard the health of EU citizens.”

The European Medicines Agency has recommended granting conditional marketing authorization for AstraZeneca’s COVID-19 vaccine.

European Medicines Agency Recommends AstraZeneca COVID-19 Vaccine for Authorization

 for industry on Jan. 19, 2021 to provide manufacturers of cell and gene therapies (CGT) with risk-based recommendations for minimizing the potential transmission of COVID-19.The guidance supplements a previous guidance document published in June 2020.

The guidance discusses source materials from donors, including cells and/or tissues. It also discusses cell expansion in culture, viral reduction steps, and formulation. “In light of SARS-CoV-2, FDA recommends that CGT product manufacturers perform a risk assessment that identifies, evaluates, and mitigates factors that may allow for transmission of SARS-CoV-2 by CGT products. A description of the risk assessment and mitigation strategies should be included in the appropriate submission to FDA (e.g., investigational new drug application [IND], biologics license application [BLA], or master file),” FDA states in the guidance document.

FDA published guidance that includes risk-based recommendations for minimizing the potential transmission of COVID-19.

Manufacturing Considerations for Cell and Gene Therapies During COVID-19

Johnson & Johnson (J&J) announced on Jan. 29, 2021 that data from a Phase III trial for its COVID-19 vaccine candidate showed that the vaccine is 66% effective overall in preventing moderate to severe COVID-19 28 days after vaccination.

The randomized double-blind, placebo-controlled clinical trial was designed to determine the safety and efficacy of a single-dose vaccine versus placebo in adults 18 years old and older, J&J said in a company press release. Participants were enrolled in the United States, Central and South America, and South Africa and the vaccine showed an effectiveness of 72% in the United States, 66% in Latin America, and 57% in South Africa, 28 days post-vaccination.

The vaccine also showed to be 85% effective in preventing severe disease across all regions studied, with efficacy against severe disease increasing over time. No cases of COVID-19 were reported in vaccinated participants after day 49, according to the press release.

“These topline results with a single-shot COVID-19 vaccine candidate represent a promising moment. The potential to significantly reduce the burden of severe disease, by providing an effective and well-tolerated vaccine with just one immunization, is a critical component of the global public health response,” said Paul Stoffels, MD, vice-chairman of the executive committee and J&J’s chief scientific officer, in the press release. “A one-shot vaccine is considered by the World Health Organization to be the best option in pandemic settings, enhancing access, distribution, and compliance. Eighty-five percent efficacy in preventing severe COVID-19 disease and prevention of COVID-19-related medical interventions will potentially protect hundreds of millions of people from serious and fatal outcomes of COVID-19. It also offers the hope of helping ease the huge burden placed on healthcare systems and communities.”

“Johnson & Johnson embarked on the global effort to combat the COVID-19 pandemic a year ago, and has brought the full force of our capabilities, as well as tremendous public-private partnerships, to enable the development of a single-shot vaccine. Our goal all along has been to create a simple, effective solution for the largest number of people possible, and to have maximum impact to help end the pandemic,” said Alex Gorsky, chairman, board of directors, and J&J’s CEO,in the press release. “We’re proud to have reached this critical milestone and our commitment to address this global health crisis continues with urgency for everyone, everywhere.”

The vaccine is 66% effective overall in preventing moderate to severe COVID-19 28 days after vaccination.

J&J’s COVID-19 Vaccine Candidate Effective in Preventing Moderate to Severe COVID-19

Novavax announced on Jan. 28, 2021 that its COVID-19 vaccine candidate, NVX-CoV2373, met the primary endpoint with a vaccine efficacy of 89.3% in a Phase III trial in the United Kingdom and a vaccine efficacy of 49% in HIV-positive participants and 60% in HIV-negative participants in a Phase IIb trial in South Africa.

The UK study, which enrolled more than 15,000 participants between 18–84 years of age, was based on the first occurrence of polymerase chain reaction (PCR)-confirmed symptomatic mild, moderate, or severe COVID-19 with onset at least seven days after the second study vaccination, Novavax said in a company press release. The analysis is based on 62 cases, of which 56 cases of COVID-19 were observed in the placebo group and six cases observed in the vaccine group, resulting in a vaccine efficacy of 89.3%.

Additionally, the vaccine showed to be effective against the UK variant strain of COVID-19. According to the press release, the strain was detected in over 50% of the PCR-confirmed symptomatic cases and, based on PCR performed on strains from 56 of the 62 cases, the vaccine showed 85.6% efficacy against the UK variant strain.

“These are spectacular results, and we are very pleased to have helped Novavax with the development of this vaccine,” said Clive Dix, Chair, UK Vaccine Taskforce, in the press release. “The efficacy shown against the emerging variants is also extremely encouraging. This is an incredible achievement that will ensure we can protect individuals in the UK and the rest of the world from this virus.”

The Phase IIb study in South Africa enrolled 4400 participants and showed a 60% efficacy for the prevention of mild, moderate, and severe COVID-19 in the population of the study that was HIV-negative, Novavax said in the press release. For the HIV-positive population, the vaccine was 49% effective in preventing the disease.

“The 60% reduced risk against COVID-19 illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the first COVID-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa,” said Professor Shabir Maddi, executive director of the Vaccines and Infectious Diseases Analytics Research Unit at Wits, and principal investigator in the Novavax COVID-19 vaccine trial in South Africa, in the press release. “I am encouraged to see that Novavax plans to immediately begin clinical development on a vaccine specifically targeted to the variant, which together with the current vaccine is likely to form the cornerstone of the fight against COVID-19.”

The vaccine met the primary endpoint with a vaccine efficacy of 89.3% in its Phase III trial in the United Kingdom and a vaccine efficacy of 49% in HIV-positive participants and 60% in HIV-negative participants in a South African Phase IIb trial. 

Novavax Shares Data from UK and South Africa COVID-19 Vaccine Candidate Trials 

 on Jan. 27, 2021 that is voluntarily recalling one lot of Cisatracurium Besylate Injection, USP 10mg per 5mL after a portion of Lot C11507A of cartons labeled as Cisatracurium Besylate Injection, USP 10mg per 5mL was found to contain 10 vials mislabeled as Phenylephrine Hydrochloride Injection, USP 100mg per 10mL.

According to the company, Cisatracurium Besylate Injection is a “nondepolarizing neuromuscular blocker”, and if a patient received phenylephrine instead of cisatracurium as part of general anesthesia, it “could cause a hyperadrenergic state resolution in elevated blood pressure, arrhythmia, and cardiac/brain ischemia. If this is not quickly diagnosed and treated, severe illness or death can occur.”

The affected lot, C11507A, EXP. October 2021, was distributed to wholesalers nationwide in the United States. The company has not received any reports of adverse events associated with the recalled lot as of Jan. 27, 2021. Adverse events may be reported to FDA via the agency’s MedWatch program.

The company is recalling one lot of Cisatracurium Besylate Injection, USP 10mg per 5mL because of mislabeling.