Pharmaceutical Technology Editors

The European Medicines Agency announced on Oct. 19, 2022 that its Committee for Medicinal Products for Human Use (CHMP) has recommended the authorization of the adapted Spikevax COVID-19 vaccine. The new vaccine targets the Omicron subvariants BA.4 and BA.5 and the original strain of SARS-CoV-2. The recommendation is for use in adults and children 12 years and older who have already received a primary vaccination course against COVID-19.

CHMP took into account available data on the Spikevax vaccine and the authorized Spikevax bivalent Original/Omicron BA.1. According to EMA, both adapted vaccines have the same composition. The decision by CHMP was also based on the quality and manufacturing process that meets quality standards in the European Union. Non-clinical laboratory data also showed that the adapted vaccine triggered an adequate immune response.

“Based on all these data and the similar composition of the adapted vaccines, the CHMP concluded that Spikevax bivalent Original/Omicron BA.4-5 is expected to be more effective than the originally authorized vaccine at triggering an immune response against the BA.4 and BA.5 subvariants. The vaccine’s safety profile is expected to be comparable to that of Spikevax bivalent Original/Omicron BA.1 and the originally authorized Spikevax, for which a large amount of data is available,” the agency stated in a press release.

The opinion now goes to the European Commission for final adoption.

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The agency has recommended authorization of the Spikevax COVID-19 vaccine that targets the Omicron variants BA.4 and BA.5.

EMA Recommends Adapted Spikevax Vaccine

Gilead Sciences and MarcoGenics, a biopharmaceutical company focused on monoclonal antibody therapies, announced an exclusive option and collaboration agreement on Oct. 17, 2022. Gilead will pay $60 million upfront for the option to license MGD023, an investigational bispecific antibody, as well as two additional bispecific research programs. MacroGenics will be eligible for up to $1.7 billion in target nomination and option fees as well as development, regulatory and commercial milestones; should it reach commercialization, the company will also be entitled to various tiered royalties.

According to Gilead’s press release, MGD024 is currently being investigated as a potential treatment for certain blood cancers, such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The antibody was formed using MacroGenics DART platform to bind interleukin 3 receptor α and cluster of differentiation 2 (CD2). It also incorporates a cluster of differentiation 3 (CD3) components that are designed to minimize cytokine-release syndrome (CRS), a potentially life-threatening toxicity, while also increasing the magnitude of antitumor activity with a longer half-life to enable intermittent dosing.

Per the terms of the agreement, MacroGenics is responsible for the ongoing Phase I study for the MGD023. The study includes a dose escalation segment and an expansion segment intended to evaluate it as a monotherapy and in combination with various other therapies. Gilead may elect to exercise its licensing option at predefined decision points.

“MacroGenics’ bispecific expertise naturally complements Gilead’s portfolio strengths in immuno-oncology and our growing hematology franchise,” said Bill Grossman, senior VP, oncology clinical development, Gilead Sciences, in the release. “We believe MGD024, with its potential to reduce CRS and permit intermittent dosing through a longer half-life, could translate to more patient-friendly dosing and enhanced clinical outcomes for people living with AML and MDS. This partnership is the latest in our efforts to develop and advance transformative new cancer therapies as we deepen our portfolio across oncology indications.”

“Rapid advances over the last decade have made CD123 a very promising target in oncology research,” said Scott Koenig, president and CEO of MacroGenics, in the release. “Advancing our bispecific DART molecule, MGD024, through a strategic collaboration with the team at Gilead will accelerate our ability to drive further development of MGD024 to the potential benefit of people living with blood cancers.”

Gilead and MacroGenics will work together on bispecific antibodies for the treatment of blood cancers.

Gilead and MacroGenics Enter $1.7 Billion Oncology Collaboration

The European Medicines Agency (EMA) announced on Oct. 14, 2022 that it would recommend a marketing authorization for Atara Biotherapeutics’ Evallo (tabelceleucel) for the treatment of patients with relapsed or refractory Epstein-Barr virus-positive post-transplant lymphoproliferative disease (R/R EBV+ PTLD). Tabelceleucel would be the first treatment indicated for the condition, which occurs because of immunosuppressive medicines taken following either solid organ or bone marrow transplantation. The most common variant is associated with EBV.

According to an EMA press release, tabelceleucel is a T-cell–based therapy that targets and eliminates infected cells. The T-cells are mixed with B-cells from the same donor that has been infected with EPV so that the T-cells recognize infected B-cells. When given to the patient, this allows them to attack and kill the patient’s own infected B-cells and help control cancers associated with the virus.

EMA based its recommendations on the results of an ongoing multicenter, Phase III, single-arm, open-label clinical trial investigating its efficacy in 43 patients with R/R EBV+ PTLD who had received at least one prior therapy. Approximately half of the treated subjects achieved partial or complete remission, while a significant number responded to the treatment with a durable response of six months or more without disease signs or symptoms post-treatment.

Ebvallo (tabelecleucel) would be the first EMA-approved therapy for patients with relapsed or refractory Epstein-Barr virus positive post-transplant lymphoproliferative disease.

Post-Transplant Lymphoproliferative Disease Treatment Receives Marketing Authorization Recommendation from EMA

The European Medicines Agency (EMA) human medicines committee (CHMP) announced a positive indication for Takeda’s dengue tetravalent vaccine (live, attenuated) on Oct. 14, 2022. The vaccine is designed to prevent disease caused by virus serotypes 1, 2, 3, and 4 in individuals four and older.

Dengue is a mosquito-borne tropical disease caused by four types of the dengue virus, typically resulting in mild flu-like symptoms. However, severe disease can also occur, resulting in potentially fatal bleeding and organ damage, particularly in individuals who have been infected a second time. According to the World Health Organization, the disease is currently endemic in more than 100 countries (including in Europe) and is estimated to have 390 million infections and result in 20,000 to 25,000 deaths per year, primarily in children (1).

According to an EMA press release, antiviral therapies for the infection are not currently available; most current measures rely on mosquito control. While an approved vaccine does exist, the agency stated that the tetravalent vaccine addressed a global unmet public health need because it demonstrated wider protection for young children and people older than 45 years old. Across 19 clinical trials of more than 27,000 individuals, the vaccine was found to reduce fever, severe disease, and hospitalization from any of the virus’ four serotypes.

The CHMP reviewed this product under the “EU-Medicines for all” program, which is meant to support parallel applications in Europe and the rest of the world. According to the release, this centralized procedure is meant to accelerate the adoption of innovative or generic medicines and vaccines while avoiding duplication of efforts from regulators.

World Health Organization, “Dengue and Severe Dengue,” Press Release, Jan. 10, 2022.

Takeda’s dengue vaccine is designed to prevent disease caused by virus serotypes 1, 2, 3, and 4 in individuals four and older.

EMA Announces Positive Indication for Takeda’s Dengue Vaccine

Moderna announced on Oct. 12, 2022 that Merck, known as MSD outside the United States and Canada, had exercised its $250 million option to jointly develop and commercialize a personalized cancer vaccine (PCV), mRNA-4157/V940. The vaccine is currently being evaluated in a Phase II clinical trial in combination with pembrolizumab, Merck’s anti-programmed cell death protein 1 (PD-1), as an adjuvant treatment for patients with high-risk melanoma.

Under the agreement, originally established in 2016 and amended in 2018, the companies will collaborate on development and commercialization of Moderna’s PCVs, including mRNA-4157/V940. According to a company press release, costs and profits will be shared equally between the two companies.

"We have been collaborating with Merck on PCVs since 2016, and together we have made significant progress in advancing mRNA-4157 as an investigational personalized cancer treatment used in combination with [pembrolizumab]," said Stephen Hoge, President, Moderna, in the release. "With data expected this quarter on PCV, we continue to be excited about the future and the impact mRNA [messenger RNA] can have as a new treatment paradigm in the management of cancer. Continuing our strategic alliance with Merck is an important milestone as we continue to grow our mRNA platform with promising clinical programs in multiple therapeutic areas."

"This long-term collaboration combining Merck's expertise in immuno-oncology with Moderna's pioneering mRNA technology has yielded a novel tailored vaccine approach," said Eliav Barr, senior vice-president and head of global clinical development, chief medical officer, Merck Research Laboratories, in the release. "We look forward to working with our colleagues at Moderna to advance mRNA-4157/V940 in combination with [pembrolizumab] as it aligns with our strategy to impact early stage disease."

Merck has exercised a $250 million option with Moderna to jointly develop and commercialize cancer vaccine mRNA-4157/V940.

Merck and Moderna Enter $250 Million Cancer Vaccine Partnership

Alexion, a group within AstraZeneca focused on rare diseases, recently announced a definitive agreement to acquire LogicBio Therapeutics, a genomic medicines company. The deal, which is expected to close in November 2022, will see Alexion purchase all outstanding shares of LogicBio for $2.07 per share; a total sum was not disclosed.

According to a press release from Oct. 3, 2022, the intent of the acquisition is to grow Alexion’s genomic medicines through LogicBio’s technology as well as that company’s experienced rare disease R&D team and expertise in preclinical development. LogicBio has developed various technology platforms for the delivery and insertion of genes to address genetic diseases. The company has also designed a platform to improve the viral vector manufacturing process.

"The proposed acquisition of LogicBio is a significant development for our growing research in genomic medicine,” said Marc Dunoyer, CEO, Alexion, in the release. “LogicBio’s people, experience, and platforms provide new scientific capabilities by adding best-in-class technology and expertise to our genomic medicine strategy. The scientific collaboration between Alexion and AstraZeneca has been a substantial area of focus since last year’s acquisition and the addition of LogicBio will expand this foundational work.”

“We are excited about the opportunity to bring our science and expertise in genetic medicine to Alexion, which shares our commitment to discovering treatments for rare conditions and improving the lives of patients,” said Fred Chereau, president and CEO, LogicBio, in the release. Through this acquisition, we strive to accelerate our research in gene editing and AAV capsid development and together move the field of genomic medicine forward.”

Alexion’s acquisition of LogicBio is designed to accelerate the company’s growth in genomic medicines.