publication date: Sep. 27, 2019

Drugs & Targets

FDA approves Janssen’s Darzalex for new multiple myeloma indication

FDA approved Darzalex (daratumumab) Sept. 26 in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed adult patients with multiple myeloma who are eligible for autologous stem cell transplant.

The Janssen Pharmaceutical Companies of Johnson & Johnson sponsors Darzalex.

The approval is based on results from the phase III CASSIOPEIA (MMY3006) study that showed the addition of Darzalex to VTd before and after ASCT resulted in deeper responses, as indicated by the higher stringent complete response rate, and improved progression-free survival compared to VTd alone. The approval comes after  FDA granted Priority Review for the supplemental Biologics License Application.

“The pivotal phase III CASSIOPEIA study is one of the largest transplant studies ever conducted in multiple myeloma, and the largest study conducted with daratumumab,” said Philippe Moreau, principal investigator and head of the hematology department at the University Hospital of Nantes, France. “It’s important that patients get a deep response from their frontline therapy, and CASSIOPEIA demonstrates that the addition of daratumumab to VTd before and after transplant markedly increased depth of response compared to VTd alone for patients with newly diagnosed multiple myeloma.”

Data from the phase III CASSIOPEIA study were first presented at the 2019 American Society of Clinical Oncology Annual Meeting and simultaneously published in The Lancet. Additionally, updates from the study were recently presented at the 17th International Myeloma Workshop Meeting.

CASSIOPEIA is a two-part, Intergroupe Francophone du Myelome study in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology and Janssen Research & Development, LLC. Results from this first part of the trial showed that the primary endpoint of sCR rate post consolidation was significantly higher in the Darzalex-VTd arm compared to VTd alone (29% vs. 20%) (Odds Ratio = 1.60; 95% confidence interval, 1.21–2.12; P=0.0010). The addition of Darzalex to VTd at a median follow-up of 18.8 months resulted in a 53% reduction in the risk of disease progression or death compared to VTd alone (Hazard Ratio [HR] = 0.47; 95% CI, 0.33–0.67; P<0.0001).1

After consolidation, Darzalex-VTd also increased the rate of complete response or better (39% vs. 26%) (OR = 1.82; 95% CI, 1.40-2.36) and very good partial response or better (83% vs. 78%) (OR = 1.41; 95% CI, 1.04-1.92) compared to VTd alone, respectively.

“The Darzalex clinical development program has led to many important firsts, but more importantly, it has generated key insights and understanding into the biology and treatment of multiple myeloma,” said Craig Tendler, vice president of clinical development and global medical affairs in oncology at Janssen Research & Development, LLC.

This news comes on the heels of the second approval of Darzalex for treatment of newly diagnosed patients with multiple myeloma who are transplant-ineligible, based on the phase III MAIA study.

 

Cologuard gets FDA approval for use in younger patients indication

FDA has approved the Exact Sciences Corp. noninvasive colorectal cancer screening test, Cologuard, for eligible average-risk individuals ages 45 and older, expanding on its previous indication for ages 50 and older.

Backed by science and clinical research in collaboration with Mayo Clinic, Cologuard is a stool DNA-based colorectal cancer screening test for average-risk individuals. Cologuard uses a biomarker panel that analyzes a person’s stool sample for 10 DNA markers, as well as blood in the stool (hemoglobin).

Last year, the American Cancer Society updated its colorectal cancer screening guidelines to include people between the ages of 45 to 49. The prior ACS recommendation called for screening to begin at age 50 (The Cancer Letter, June 1, 2018).

The label expansion, or broadening of the population for whom Cologuard is FDA-approved, extends screening to approximately 19 million average-risk people in the U.S. ages 45-49.

“About three million people have been screened for colorectal cancer with Cologuard, with nearly half of those surveyed saying they were previously unscreened. With the FDA now approving the use of Cologuard for this vulnerable 45-49 age group, we are giving health care providers a sensitive, noninvasive option that has the potential to help combat the rise of colorectal cancer rates among this younger group of people,” Exact Sciences Chair and CEO Kevin Conroy said in a statement.

Exact Sciences has designed a nationwide user-navigation system that provides 24/7 phone and online support to help people through the process of collecting and returning their samples.

 

Astellas gets CHMP nod for Xospata as monotherapy for an AML indication

The European Medicines Agency recommended approval for the oral once-daily therapy Xospata (gilteritinib) as a monotherapy for the treatment of adult patients who have relapsed or refractory (resistant to treatment) acute myeloid leukemia with a FLT3 mutation (FLT3mut+).

The Committee for Medicinal Products for Human Use gave the positive opinion. If approved by the European Commission, Xospata  has the potential to improve treatment outcomes for AML patients with the most common mutations – FLT3 internal tandem duplication and FLT3 tyrosine kinase domain–and would be one of the few advances for the treatment of AML in Europe over the past 40 years.

Xospata received accelerated assessment from the EMA, which allowed the CHMP to reduce the timeframe for approval. Astellas Pharma Inc. sponsors Xospata.

“The data are encouraging, showing a significant improvement in overall survival, and one-year survival rates doubled when comparing gilteritinib to the current standard of care,” study investigator Giovanni Martinelli, Institute of Hematology, S.Orsola-Malpighi University Hospital, Bologna, Italy, said in a statement. “For relapsed or refractory FLT3mut+ AML patients the current prognosis is poor, with median OS of less than six months following treatment with salvage chemotherapy. If approved by the EC, gilteritinib has the potential to change the treatment landscape.”

The CHMP decision is based on results from the phase III ADMIRAL trial, which investigated Xospata versus salvage chemotherapy in patients with relapsed or refractory FLT3mut+ AML. Patients treated with gilteritinib had significantly longer OS than those who received salvage chemotherapy. Median OS for patients who received gilteritinib was 9.3 months, compared to 5.6 months for patients who received salvage chemotherapy (Hazard Ratio = 0.64 (95% CI 0.49, 0.83), P=0.0004). Rates of one-year survival were 37% for patients who received Xospata, compared to 17% for patients who received salvage chemotherapy.

In late 2018, Xospata was approved by regulatory agencies in the United States and Japan for the treatment of adult patients who have relapsed or refractory FLT3mut+ AML.

 

CHMP recommends approval for Bavencio + Axitinib for first-line treatment of advanced RCC

The European Medicines Agency Sept. 20 recommended approval of Bavencio (avelumab) in combination with axitinib for the first-line treatment of adult patients with advanced renal cell carcinoma.

The Committee for Medicinal Products for Human Use gave the positive opinion based on positive findings from the phase III JAVELIN Renal 101 study, which demonstrated a significant extension in median progression-free survival and a clinically meaningful improvement in objective response rate for the combination across all prognostic risk groups compared with sunitinib.

The European Commission will review the opinion, with a decision anticipated in the fourth quarter of this year. Bavencio is sponsored by EMD Serono and Pfizer.

FDA approved Bavencio in combination with axitinib for the first-line treatment of patients with advanced RCC in May 2019. A supplemental application for Bavencio in combination with axitinib in unresectable or metastatic RCC was submitted in Japan in Jan. 2019.

 

Celsius Therapeutics brings genomics platform to three institutions worldwide

Celsius Therapeutics will apply its proprietary single-cell genomics platform to tissue samples from patients receiving immune checkpoint inhibitor therapies for triple-negative breast cancer, bladder cancer and kidney cancer, at cancer care providers in three countries.

The Parker Institute for Cancer Immunotherapy in San Francisco, Institut Gustave Roussy in Paris, and the University Health Network in Toronto, have access to the single-cell genomics platform. The goal of the collaboration is to discover novel molecular mechanisms and targets for drug discovery.

“The heterogeneity of response in immunotherapy studies suggests that a deeper understanding of disease biology and patient subpopulations is needed to fully realize the potential of this approach,” Celsius CEO Tariq Kassum said in a statement.

Under these agreements, Celsius will apply its platform approach to generate single-cell data from patient biopsy samples taken pre- and post-treatment with checkpoint inhibitors. In each case, Celsius retains the ability to integrate the clinical information and single-cell genomics data generated from the studies into its growing database. The company plans to use its machine learning algorithms and functional genomics capabilities to rapidly identify and prioritize targets for drug discovery.

 

Evotec, Takeda collaborate on drug discovery

Evotec SE and Takeda Pharmaceutical Co. Ltd. established at least five joint drug discovery programs.

The goal is for  Evotec to deliver clinical candidates for Takeda to pursue into clinical development.

“Collaborating with world-class drug discovery partners like Evotec is central to our model for discovering and developing transformative medicines,” Global Head of Research at Takeda Steve Hitchcock said in a statement. “Takeda has a long history of working with Evotec and is confident in Evotec’s capabilities.”

The collaboration combines Evotec’s ability to drive fully integrated drug discovery programs with Takeda’s insights into therapeutic approaches in Takeda’s four core therapeutic areas: oncology, gastroenterology, neuroscience and rare diseases, in addition to Takeda’s insight into development and commercialization.

Evotec will leverage its discovery platform to validate therapeutic hypotheses and advance small molecule programs. Takeda will have options to assume responsibility at lead series when Evotec delivers a preclinical candidate.

Takeda will pay Evotec a one-time, upfront fee to access its platforms. Additionally, Evotec is eligible to receive preclinical, clinical and commercial milestones that can total more than $170 million per program as well as tiered royalties on future sales.

 

Foundation Medicine, Natera to advance personalized cancer monitoring

Foundation Medicine Inc. and Natera Inc. will collaborate to develop and commercialize personalized circulating tumor DNA monitoring assays, which biopharmaceutical and clinical customers who order FoundationOne CDx would be able to access.

The partnership’s focus will be to enable ctDNA monitoring in biopharmaceutical trials in 2020 to establish the clinical utility for these novel assays. Following these studies, a monitoring product will be made available to clinical customers.

“Cancer monitoring is an important part of patient care and developing innovative and more efficient diagnostics for physicians to identify disease progression and therapy resistance earlier is critical,” Foundation Medicine CEO Cindy Perettie said in a statement.

The companies will leverage Foundation Medicine’s FoundationOne CDx as the baseline test to define a set of unique variants that will subsequently be monitored using a co-developed assay that includes components of Natera’s Signatera platform.

The initial focus is to develop personalized cancer monitoring assays that are compatible with FoundationOne CDx as the baseline test, but Foundation Medicine may also elect to expand the scope of the partnership to develop monitoring assays that utilize genomic data generated from Foundation Medicine’s FoundationOne Liquid test for solid tumors utilizing ctDNA and/or FoundationOne Heme test for hematologic malignancies and sarcomas.

Foundation Medicine has the exclusive right to commercialize the co-developed monitoring assays. Natera will continue to exclusively offer Signatera testing based on whole exome sequencing of tumor and matched normal DNA.

Foundation Medicine’s tests are ordered by physicians for more than 100,000 patients per year, and the company has more than 50 active biopharma partnerships, the company said.

 

Adaptive Biotechnologies, Amgen use clonoSEQ as preferred MRD test

Adaptive Biotechnologies Corp. entered into a global agreement with Amgen to use Adaptive’s next-generation sequencing-based clonoSEQ Assay to assess minimal residual disease across multiple drug development programs within the Amgen hematology portfolio.

Under the four-year agreement, Adaptive will receive annual development fees in addition to sequencing payments and regulatory milestones in exchange for providing MRD testing and analysis for ongoing and future clinical trials.   

The partnership, which began in 2016 to assess MRD in acute lymphoblastic leukemia, demonstrates the increasing utility of MRD assessment in the clinic. Adaptive will leverage data generated under this partnership to continue building robust evidence that supports MRD as a validated measure of patient outcomes across multiple novel treatments and blood cancers.

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