publication date: Jan. 19, 2018

Drugs and Targets

Foundation Medicine and Pfizer form partnership to develop companion diagnostics

Foundation Medicine Inc. said the company has entered into a broad partnership with Pfizer Inc.

The partnership focuses on development, regulatory support and commercialization of companion diagnostics that will be included in updates to FoundationOne CDx.

FoundationOne CDx is Foundation Medicine’s FDA-approved comprehensive genomic profiling assay for all solid tumors that incorporates multiple companion diagnostics.

Pfizer will also benefit from access to FoundationInsights, Foundation Medicine’s data analytics platform, to facilitate novel biomarker discovery and to optimize clinical trial design. The unique combination of FoundationInsights and FoundationOne CDx will potentially enable Pfizer to leverage Foundation Medicine’s platform technology to accelerate discovery and development of precision oncology therapeutics.

Pfizer currently has 10 FDA-approved oncology medicines that treat a diverse array of solid tumors and hematologic malignancies. In addition, its oncology pipeline includes 17 assets in clinical development and 19 phase III studies.

FoundationOne CDx assesses all classes of genomic alterations in 324 genes known to drive cancer growth, providing potentially actionable information to help guide treatment decisions. It also reports genomic biomarkers, such as microsatellite instability and tumor mutational burden, that can help inform the use of immunotherapies; genomic alterations in other genes relevant to patient management; and relevant clinical trial information.

As such, it is designed to help streamline companion diagnostic development, mitigate risk and advance targeted therapy development. Currently FoundationOne CDx is FDA-approved as a CGP assay for all solid tumors and a broad companion diagnostic for patients with certain types of non-small cell lung cancer, melanoma, colorectal cancer, ovarian cancer or breast cancer to identify those patients who may benefit from treatment with one of 17 on-label targeted therapies.

Concurrent with FDA approval, the Centers for Medicare & Medicaid Services issued a preliminary National Coverage Determination for FoundationOne CDx. The draft NCD would provide coverage for FDA-approved companion diagnostic claims, as well as a pathway for additional coverage with evidence development in other solid tumor types. The final policy is expected to issue during the first quarter of 2018 following public comment on the preliminary NCD and an administrative period.

FoundationOne CDx is a sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability and tumor mutational burden using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens.

FoundationOne CDx is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling.

Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms.


FDA approves addition of overall survival data to Kyprolis

FDA has approved the supplemental New Drug Application to add overall survival data from the phase III head-to-head ENDEAVOR trial to the Prescribing Information for Kyprolis (carfilzomib).

Data added to the label demonstrated that Kyprolis and dexamethasone reduced the risk of death by 21 percent and increased OS by 7.6 months versus Velcade (bortezomib) and dexamethasone in patients with relapsed or refractory multiple myeloma (median OS 47.6 months for Kd versus 40.0 months for Vd, HR=0.79; p=0.01).

The NCCN Clinical Practice Guidelines in Oncology list Kd as the only preferred doublet regimen at relapse for multiple myeloma. Full OS results from the ENDEAVOR trial were published earlier this year in The Lancet Oncology.

Adverse events observed in this updated analysis were consistent with those previously reported for ENDEAVOR. The most common adverse events (greater than or equal to 20 percent) in the Kyprolis arm were anemia, diarrhea, pyrexia, dyspnea, fatigue, hypertension, cough, insomnia, upper respiratory tract infection, peripheral edema, nausea, bronchitis, asthenia, back pain, thrombocytopenia and headache.

Since its approval in 2012, more than 50,000 patients worldwide have received Kyprolis. The Kyprolis clinical program continues to focus on providing treatment options for physicians and patients for this frequently relapsing and difficult-to-treat cancer. Kyprolis is available for patients whose myeloma has relapsed or become resistant to another treatment and continues to be studied in a range of combinations and patient populations.

The randomized ENDEAVOR (RandomizEd, OpeN Label, Phase III Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) trial of 929 patients evaluated Kyprolis in combination with low-dose dexamethasone, versus Velcade with low-dose dexamethasone in relapsed or refractory patients who previously received at least one, but not more than three, prior therapeutic regimens.

The primary endpoint of the trial was progression-free survival, defined as the time from treatment initiation to disease progression or death. The primary analysis was published in The Lancet Oncology and is described in the Prescribing Information.

Patients received treatment until progression with Kyprolis as a 30-minute infusion on days 1, 2, 8, 9, 15 and 16 of 28 day treatment cycles, along with low-dose dexamethasone (20 mg). For cycle one only, Kyprolis was administered at 20 mg/m2 on days 1 and 2, and if tolerated was escalated to 56 mg/m2 from day 8 of cycle one onwards. Patients who received Velcade (1.3 mg/m2) with low-dose dexamethasone (20 mg) were treated with Velcade administered subcutaneously or intravenously at the discretion of the investigator and in accordance with regional regulatory approval of Velcade. More than 75 percent of the patients in the control arm received Velcade subcutaneously.


Novartis granted FDA Priority Review for Kymriah for adults with r/r DLBCL

Novartis said its supplemental Biologics License Application for Kymriah (tisagenlecleucel) suspension for intravenous infusion, formerly CTL019, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma who are ineligible for or relapse after autologous stem cell transplant (ASCT) has been accepted by FDA for Priority Review.

In addition, the European Medicines Agency has granted accelerated assessment to the Marketing Authorization Application for Kymriah for the treatment of children and young adults with r/r B-cell acute lymphoblastic leukemia and for adult patients with r/r DLBCL who are ineligible for ASCT.

Kymriah became the first CAR-T cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.

Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and the University of Pennsylvania entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

The regulatory applications in the US and EU are based on data from the Novartis-sponsored global clinical trial program of Kymriah in children and young adults with r/r B-cell ALL and adult patients with r/r DLBCL demonstrating the efficacy and safety of Kymriah across studies. Results from the pivotal phase II JULIET clinical trial served as the basis of the sBLA and MAA (applications submitted by pharmaceutical companies to health authorities when seeking approval of a new product) for Kymriah in adult patients with r/r DLCBL. Results from the pivotal phase II ELIANA study were submitted as part of the MAA for Kymriah in children and young adults with r/r B-cell ALL.

JULIET is the first multi-center global registration study for Kymriah in adult patients with r/r DLBCL. JULIET is the largest study examining a CAR-T therapy in DLBCL, enrolling patients from 27 sites in 10 countries across the US, Canada, Australia, Japan and Europe, including: Austria, France, Germany, Italy, Norway and the Netherlands. Data from the six-month primary analysis of JULIET were presented at the annual meeting of the American Society of Hematology (ASH) in December 2017.

ELIANA is the first pediatric global CAR-T cell therapy registration trial, examining patients in 25 centers in the US, Canada, Australia, Japan, and the EU, including: Austria, Belgium, France, Germany, Italy Norway, and Spain.

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