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Kyowa Kirin Announces Final Safety Data of POTELIGEO® (mogamulizumab-kpkc) from MAVORIC Trial

On January 31, 2020 Kyowa Kirin, Inc., (Kyowa Kirin, TSE: 4151) reported the final safety data from the MAVORIC (Mogamulizumab anti-CCR4 Antibody Versus ComparatOR In CTCL) trial of mogamulizumab-kpkc, which will be presented at the 12th Annual T-Cell Lymphoma Forum (TCLF) in La Jolla, California (Press release, Kyowa Hakko Kirin, JAN 31, 2020, View Source [SID1234553745]).

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MAVORIC is the first pivotal trial in cutaneous T-cell lymphoma (CTCL) to use progression-free survival (PFS) as a primary endpoint. It is also the largest randomized study to compare systemic therapies in subtypes of CTCL.1 Secondary endpoints included a proportion of patients achieving an overall response rate (ORR), duration of response and safety.1 Primary results were based on a data cutoff of December 31, 2016, which served as the basis of the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approvals of mogamulizumab for the treatment of the most common subtypes of CTCL as well as a partial change of the product label in Japan.1 The analysis being presented at TCLF reports final safety results of MAVORIC as of the safety data available on January 3, 2019, based on patients who continued participating in the trial post-approval.2

For the final safety analysis, median duration of follow-up was 34.5 months (range, 0.13-70.0).2 Median treatment exposure was 170 days (range, 1-1813) for mogamulizumab and 84 days (4‑1230) for vorinostat, which represent the same median values but broader ranges compared to the primary analysis (primary analysis, 170 days [1-1379] for mogamulizumab and 84 days [4-1058] for vorinostat).2

This final safety analysis from the MAVORIC study in patients with previously treated mycosis fungoides (MF) and Sézary syndrome (SS) demonstrated that mogamulizumab did not identify any new safety signals. The type and frequency of adverse events (AEs) in either the mogamulizumab or vorinostat treatment groups were consistent with those reported in the primary analysis.2 Treatment-emergent adverse events (TEAEs), regardless of causality, were reported at similar rates in the two treatment groups and included constipation, peripheral edema, headache, and anemia.2 TEAEs that occurred at higher frequency in the mogamulizumab vs. vorinostat arm included infusion-related reaction (33.2% vs 0.5%) and drug eruption (25.0% vs 1.1%).2 The majority of these events were grade 1 or 2, and the types and frequencies of AEs attributable to mogamulizumab included infusion-related reaction (33.2% [61/184]), drug eruption (23.9% [44/184]), and fatigue (18.5% [34/184]).2 AEs attributed to vorinostat included diarrhea (55.4% [103/186]), nausea (38.2% [71/186]), and fatigue (33.3% [62/186]).2

In the trial, patients on vorinostat for at least two cycles who demonstrated confirmed disease progression or experienced intolerable toxicity (grade ≥3 adverse events [AEs], excluding inadequately treated nausea, vomiting, and diarrhea; and alopecia), despite dose reduction and appropriate management of side effects, could cross over to treatment with mogamulizumab. This analysis confirmed earlier findings showing that the type and incidence of TEAEs among patients receiving mogamulizumab after crossover were similar to those observed for patients initially randomized to mogamulizumab.2

"We are pleased that this final safety analysis from the MAVORIC study in patients with previously treated MF and SS demonstrates that the additional two years of mogamulizumab safety follow up and treatment exposure did not identify any unexpected safety findings," said Jeffrey S. Humphrey, MD, Chief Development Officer of Kyowa Kirin, Inc.

POTELIGEO (mogamulizumab-kpkc) is approved in the U.S. for the treatment of adult patients with relapsed or refractory MF or SS after at least one prior systemic therapy.3 MF and SS are the most common subtypes of CTCL.4

Please see Poteligeo Indication and Important Safety Information below.

INDICATION
POTELIGEO (mogamulizumab-kpkc) injection, for intravenous infusion is indicated for the treatment of adult patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after at least one prior systemic therapy.

Important Safety Information
Warnings and Precautions:

Dermatologic toxicity: Monitor patients for rash throughout the course of treatment. For patients who experienced dermatologic toxicity in Trial 1, the median time to onset was 15 weeks, with 25% of cases occurring after 31 weeks. Interrupt POTELIGEO for moderate or severe rash (Grades 2 or 3). Permanently discontinue POTELIGEO for life-threatening (Grade 4) rash or for any Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).
Infusion reactions: Most infusion reactions occur during or shortly after the first infusion. Infusion reactions can also occur with subsequent infusions. Monitor patients closely for signs and symptoms of infusion reactions and interrupt the infusion for any grade reaction and treat promptly. Permanently discontinue POTELIGEO for any life-threatening (Grade 4) infusion reaction.
Infections: Monitor patients for signs and symptoms of infection and treat promptly.
Autoimmune complications: Interrupt or permanently discontinue POTELIGEO as appropriate for suspected immune-mediated adverse reactions. Consider the benefit/risk of POTELIGEO in patients with a history of autoimmune disease.
Complications of allogeneic HSCT after POTELIGEO: Increased risks of transplant complications have been reported in patients who received allogeneic HSCT after POTELIGEO. Follow patients closely for early evidence of transplant-related complications.
Adverse Reactions:

The most common adverse reactions (reported in ≥ 10% of patients) with POTELIGEO in the clinical trial were rash, including drug eruption (35%), infusion reaction (33%), fatigue (31%), diarrhea (28%), drug eruption (24%), upper respiratory tract infection (22%), musculoskeletal pain (22%), skin infection (19%), pyrexia (17%), edema (16%), nausea (16%), headache (14%), thrombocytopenia (14%), constipation (13%), anemia (12%), mucositis (12%), cough (11%), and hypertension (10%).

Pfizer Receives Positive CHMP Opinion for Oncology Biosimilar, RUXIENCE™ (rituximab)

On January 31, 2020 Pfizer Inc. (NYSE: PFE) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion, recommending marketing authorization for RUXIENCE (rituximab),1 a potential biosimilar to MabThera (rituximab).2,3 RUXIENCE is a monoclonal antibody (mAb) for the treatment of non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), rheumatoid arthritis (RA), granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), and pemphigus vulgaris (PV) (Press release, Pfizer, JAN 31, 2020, View Source [SID1234553744]).1 The CHMP’s opinion will now be reviewed by the European Commission, with a regulatory decision anticipated in the first half of 2020.

"Biosimilars like RUXIENCE can play an important role in cancer care, helping to expand patient access to potentially life-changing therapies," said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global Product Development. "We are committed to bringing biosimilars like RUXIENCE to the market as a treatment option with similar safety and efficacy to the originator product at a potentially lower cost. If approved, RUXIENCE would become Pfizer’s fifth oncology biosimilar to receive regulatory approval in Europe."

The regulatory submission is supported by a comprehensive data package which demonstrates biosimilarity of RUXIENCE to the reference product. This includes results from the REFLECTIONS B3281006 clinical comparative study, which evaluated the efficacy, safety and immunogenicity, pharmacokinetics and pharmacodynamics of RUXIENCE and found no clinically meaningful differences in safety or efficacy compared to the reference product in patients with CD20-positive, low tumor burden follicular lymphoma.4

Biosimilars have been a significant catalyst for change for the healthcare industry over the last decade, with the potential to help create a more sustainable healthcare system. With more than 10 years of global in-market experience and five approved biosimilar products in Europe, Pfizer is proud to be a leader and at the forefront of this vital healthcare segment. RUXIENCE was also approved for use in the United States for the treatment of adult patients with NHL, CLL, GPA and MPA in 2019 and was recently made available to U.S. patients.

EMA Validates Seattle Genetics’ Marketing Authorization Application for Tucatinib for Patients with Locally Advanced or Metastatic HER2-Positive Breast Cancer

On January 31, 2020 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that the European Medicines Agency (EMA) validated the Marketing Authorization Application (MAA) for tucatinib, in combination with trastuzumab and capecitabine, for the treatment of adult patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received at least two prior anti-HER2 treatment regimens (Press release, Seattle Genetics, JAN 31, 2020, View Source [SID1234553743]). The EMA validation of the MAA confirms that the submission is sufficiently complete to begin the formal review process. Tucatinib is an oral, small molecule tyrosine kinase inhibitor (TKI) that is highly selective for HER2.

"Today, we achieved a significant milestone towards our goal of making tucatinib available to patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including those with brain metastases, around the world," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "We look forward to working with the EMA throughout the review process. If approved, tucatinib has the potential to be a clinically meaningful advance for patients in this disease setting."

The MAA is based on data from the pivotal HER2CLIMB clinical trial, which compared tucatinib in combination with trastuzumab and capecitabine to trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer. Patients had previously received trastuzumab, pertuzumab and T-DM1 (ado-trastuzumab emtansine). Patients had received a median of four prior lines of therapy overall and three in the metastatic setting. Forty-seven percent of the patients enrolled in the trial had brain metastases at the time of enrollment. Results of the pivotal HER2CLIMB trial were presented during an oral presentation at the 2019 San Antonio Breast Cancer Symposium (SABCS) and simultaneously published in the New England Journal of Medicine(NEJM).

The New Drug Application (NDA) for tucatinib was submitted to the U.S. Food and Drug Administration (FDA) on December 23, 2019 under the Real-Time Oncology Review Pilot Program. The review of the tucatinib NDA is also being conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among participating international partners. Tucatinib was recently granted Breakthrough Therapy designation by the FDA in combination with trastuzumab and capecitabine, for the treatment of patients with locally advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have been treated with trastuzumab, pertuzumab, and T-DM1. This designation was based on data from the HER2CLIMB trial.

About HER2CLIMB

HER2CLIMB is a multinational randomized (2:1), double-blind, placebo-controlled, active comparator, pivotal clinical trial comparing tucatinib in combination with trastuzumab and capecitabine compared with trastuzumab and capecitabine alone in patients with locally advanced unresectable or metastatic HER2-positive breast cancer who were previously treated with trastuzumab, pertuzumab and T-DM1. The primary endpoint of the trial was progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as determined by blinded independent central review (BICR) in the first 480 patients enrolled in the trial. HER2CLIMB enrolled a total of 612 patients to support the analyses of key secondary endpoints, including overall survival, PFS per BICR in patients with brain metastases at baseline and confirmed objective response rate (ORR). Safety data were evaluated throughout the study.

About HER2-Positive Breast Cancer

Patients with HER2-positive breast cancer have tumors with high levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the aggressive spread of cancer cells. An estimated 271,270 new cases of invasive breast cancer will be diagnosed in the U.S. in 2019.1 Between 15 and 20 percent of breast cancer cases worldwide are HER2-positive.2 Historically, HER2-positive breast cancer tends to be more aggressive and more likely to recur than HER2-negative breast cancer.2, 3, 4 In patients with metastatic breast cancer, the most common site of first metastasis is in bone, followed by lung, brain, and liver.5, 6 Up to 50 percent of metastatic HER2-positive breast cancer patients develop brain metastases over time.2, 7 Despite recent treatment advances, there is still a significant need for new therapies that can impact metastatic disease, especially brain metastases. There are currently no approved therapies demonstrating progression-free survival or overall survival benefit for the treatment of patients with HER2-positive metastatic breast cancer after progression on T-DM1.8, 9, 10

About Tucatinib

Tucatinib is an investigational, orally bioavailable, potent tyrosine kinase inhibitor that is highly selective for HER2 without significant inhibition of EGFR. Inhibition of EGFR has been associated with significant toxicities, including skin rash and diarrhea. Tucatinib has shown activity as a single agent and in combination with both chemotherapy and other HER2 targeted agents such as trastuzumab.1,2 Studies of tucatinib in these combinations have shown activity both systemically and in brain metastases. HER2 is a growth factor receptor that is overexpressed in multiple cancers, including breast, colorectal and gastric cancers. HER2 mediates cell growth, differentiation and survival. Tucatinib has been granted orphan drug designation by the FDA for the treatment of breast cancer patients with brain metastases.

In addition to HER2CLIMB, tucatinib is being evaluated in a randomized, double-blind, placebo-controlled, multi-center phase 3 trial of tucatinib in combination with T-DM1 compared to T-DM1 alone, in patients with unresectable locally advanced or metastatic HER2-positive breast cancer, including those with brain metastases, who have had prior treatment with a taxane and trastuzumab. The primary endpoint is PFS per RECIST criteria. Secondary endpoints include overall survival, objective response rate and duration of response. This global trial is expected to enroll approximately 460 patients. More information about the phase 3 trial, including enrolling centers, is available at www.clinicaltrials.gov.

Tucatinib is also being evaluated in a multi-center, open-label, single-arm phase 2 clinical trial known as MOUNTAINEER, which is evaluating tucatinib in combination with trastuzumab in patients with HER2-positive, RAS wildtype metastatic or unresectable colorectal cancer. The primary endpoint of the trial is ORR by RECIST criteria. PFS, duration of response, overall survival and safety and tolerability of the combination regimen are secondary objectives. Results for 26 patients were evaluated in an analysis and presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Congress. Enrollment is ongoing. More information about the MOUNTAINEER trial, including enrolling centers, is available at www.clinicaltrials.gov.

ALLERGAN TO REPORT FOURTH QUARTER AND FULL YEAR 2019 FINANCIAL RESULTS

On January 31, 2020 Allergan plc (NYSE: AGN) reported it will release fourth quarter and full year 2019 financial results on Monday, February 10, 2020, prior to the open of U.S. financial markets (Press release, Allergan, JAN 31, 2020, View Source [SID1234553742]).

For additional materials related to Allergan’s fourth quarter and full year 2019 financial results, please visit Allergan’s Investor Relations website at View Source

IMV to Present at 2020 BIO CEO & Investor Conference

On January 31, 2020 IMV Inc. (Nasdaq: IMV; TSX: IMV), a clinical-stage biopharmaceutical company pioneering a novel class of immunotherapies, reported that company management will present at the BIO CEO and Investor Conference on Monday, February 10, 2020 at 9:30 a.m. ET in New York, NY (Press release, IMV, JAN 31, 2020, View Source [SID1234553741]).

A live webcast of this presentation will be available under "Events, Webcasts and Presentations" in the investors section of the IMV website and a replay will be available approximately one hour after the presentation. Afterwards, it will be available for approximately 30 days.