publication date: Nov. 6, 2020

Drugs & Targets

Lynparza approved in the EU as first-line maintenance treatment with bevacizumab for HRD-positive advanced ovarian cancer

Lynparza (olaparib) has been approved in the European Union for the first-line maintenance treatment with bevacizumab of patients with homologous recombination deficient-positive advanced ovarian cancer.

Lynparza is sponsored by AstraZeneca and MSD.

The approval by the European Commission was based on a biomarker subgroup analysis of the PAOLA-1 phase III trial, which showed that Lynparza, in combination with bevacizumab maintenance treatment, demonstrated a substantial progression-free survival improvement versus bevacizumab alone for patients with HRD-positive advanced ovarian cancer. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency in September 2020.

The PAOLA-1 Phase III trial showed that Lynparza, in combination with bevacizumab maintenance treatment, reduced the risk of disease progression or death by 67% (based on a hazard ratio of 0.33; 95% confidence interval 0.25-0.45). The addition of Lynparza improved PFS to a median of 37.2 months versus 17.7 with bevacizumab alone in patients with HRD-positive advanced ovarian cancer. The data from the PAOLA-1 trial was published in The New England Journal of Medicine in 2019.

Further results recently presented at the European Society for Medical Oncology Virtual Congress 2020 showed a statistically significant improvement in the key secondary endpoint of the time to second disease progression. Lynparza with bevacizumab provided benefit beyond first disease progression, improving PFS2 to a median of 50.3 months versus 35.3 with bevacizumab alone.

The full EU indication is for Lynparza in combination with bevacizumab for the maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with HRD positive status defined by either a breast cancer susceptibility gene 1/2 (BRCA1/2) mutation and/or genomic instability.

Lynparza in combination with bevacizumab is approved in the U.S. and other countries as first-line maintenance treatment for HRD-positive advanced ovarian cancer and is currently under regulatory review in other countries.


Kymriah receives approval for commercial manufacturing in Japan

Japan’s Ministry of Health, Labor and Welfare has issued marketing authorization for Foundation for Biomedical Research and Innovation at Kobe to manufacture and supply commercial Kymriah (tisagenlecleucel) for patients in Japan.

Kymriah is sponsored by Novartis.

Commercial manufacturing for Kymriah now takes place at five sites globally including at the Morris Plains, New Jersey facility, where FDA approved a further increase in manufacturing capacity.

Kymriah is the first-ever FDA-approved CAR T-cell therapy, and the first-ever CAR-T to be approved in two distinct indications. Kymriah is currently approved for the treatment of r/r pediatric and young adult (up to 25 years of age) acute lymphoblastic leukemia, and r/r adult diffuse large B-cell lymphoma (DLBCL).

Kymriah, approved in both indications by the Japan MHLW in 2019, is currently the only CAR T-cell therapy approved in Asia. Clinical manufacturing began at FBRI in 2019 and will continue alongside commercial manufacturing.

Kymriah was developed in collaboration with the Perelman School of Medicine at the University of Pennsylvania.

Kymriah is currently approved for use in at least one indication in 26 countries and at more than 260 certified treatment centers.


Merck to acquire VelosBio for $2.75 billion

Merck and VelosBio Inc. have entered into a definitive agreement, where Merck, through a subsidiary, will acquire all outstanding shares of VelosBio for $2.75 billion in cash.

VelosBio is a privately held clinical-stage biopharmaceutical company committed to developing first-in-class cancer therapies targeting receptor tyrosine kinase-like orphan receptor 1.

VelosBio’s lead investigational candidate is VLS-101, an antibody-drug conjugate targeting ROR1 that is being evaluated in a phase I and a phase II clinical trial for the treatment of hematologic malignancies and solid tumors.

In October 2020, VelosBio began a phase II clinical trial (NCT04504916) to evaluate VLS-101 for the treatment of patients with solid tumors, including patients with triple-negative breast cancer, hormone receptor-positive and/or HER2-positive breast cancer, and non-squamous non-small-cell lung cancer.

In early clinical trials, VLS-101 demonstrated a manageable safety profile and early signs of anti-tumor activity. Results of a phase I clinical trial, to be presented virtually at the American Society of Hematology Annual Meeting (Dec. 5-8, 2020), showed that VLS-101 resulted in objective clinical responses, including complete responses, in 47% (n=7/15) of patients with mantle cell lymphoma (MCL) and 80% (n=4/5) of patients with diffuse large B-cell lymphoma.

Patients in this phase I trial had been heavily pretreated with other anticancer medications, and their cancers had failed to respond or had relapsed after initially responding to these other anticancer medications. In addition, VelosBio is developing a preclinical pipeline of next-generation ADCs and bispecific antibodies targeting ROR1 with the potential to complement VLS-101 by offering alternative methods of tumor cell killing.

The closing of the transaction, which is subject to approval under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions, is expected by the end of 2020.

Merck was represented by Gibson Dunn & Crutcher LLP as legal advisor and J.P. Morgan Securities LLC as financial advisor. VelosBio was represented by Cooley LLP as legal advisor and Centerview Partners LLC as financial advisor.

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