Amgen Announces Phase 3 CANDOR Study Combining KYPROLIS® (carfilzomib) And DARZALEX® (daratumumab) Meets Primary Endpoint Of Progression-Free Survival

THOUSAND OAKS, Calif., Sept. 13, 2019 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the Phase 3 CANDOR study evaluating KYPROLIS(®) (carfilzomib) in combination with dexamethasone and DARZALEX(®) (daratumumab) (KdD) compared to KYPROLIS and dexamethasone alone (Kd) met its primary endpoint of progression-free survival (PFS). The regimen resulted in a 37% reduction in the risk of progression or death in patients with relapsed or refractory multiple myeloma treated with KdD (HR=0.630; 95% CI: 0.464, 0.854; p=0.0014). The median PFS for patients treated with Kd alone was 15.8 months, while the median PFS for patients treated with KdD has not been reached by the cut-off date.

"The potential to combine KYPROLIS with DARZALEX, two powerful targeted agents, represents an additional therapeutic approach for patients with relapsed or refractory multiple myeloma," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "The results from the CANDOR study confirm the potential for KYPROLIS to be used in combination with an anti-CD38 monoclonal antibody."

There was a higher frequency of adverse events reported in KdD, a three-agent regimen, than in Kd, a two-agent regimen. The types of observed adverse events were consistent with the known safety profiles of the individual agents. The most frequently reported treatment-emergent adverse events (greater than or equal to 20%) in the KdD arm were thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue and dyspnea.

"While treatment advances have improved outcomes for patients with multiple myeloma, there remains a need for additional therapeutic options for patients who have relapsed," said Ajai Chari, M.D., associate professor of medicine, the director of clinical research in the Multiple Myeloma Program and the associate director of clinical research, Mount Sinai Cancer Clinical Trials Office. "CANDOR confirms in a large Phase 3 study the benefit for patients demonstrated in the earlier Phase 1 study using the same combination."

The CANDOR data will be submitted to a future medical meeting and discussed with health authorities in preparation for regulatory submissions.

About CANDOR
CANDOR, a randomized, open-label Phase 3 study of KYPROLIS, dexamethasone and DARZALEX (KdD) compared to KYPROLIS and dexamethasone (Kd), has evaluated 466 relapsed or refractory multiple myeloma patients who have received one to three prior therapies. Patients were treated until disease progression. The primary endpoint was PFS, and the key secondary endpoints were overall response rate, minimal residual disease and overall survival. PFS was defined as time from randomization until disease progression or death from any cause.

In the first arm, patients received KYPROLIS twice weekly at 56 mg/m(2) and dexamethasone in combination with DARZALEX. In the second arm (control), patients received KYPROLIS twice weekly at 56 mg/m(2 )and dexamethasone.

CANDOR was initiated as part of a collaboration with Janssen, and under the terms of the agreement, Janssen co-funded the study. For more information about this trial, please visit www.clinicaltrials.gov under trial identification number NCT03158688.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer, characterized by a recurring pattern of remission and relapse.(1) It is a rare and life-threatening disease that accounts for approximately one percent of all cancers.(2,3) Worldwide, approximately 160,000 people are diagnosed with multiple myeloma each year, and 106,000 patient deaths are reported on an annual basis.(2)

About KYPROLIS(®) (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.(4) KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.(5) In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.(4,5)

Since its first approval in 2012, approximately 130,000 patients worldwide have received KYPROLIS. KYPROLIS is approved in the U.S. for the following:

    --  In combination with dexamethasone or with lenalidomide plus
        dexamethasone for the treatment of patients with relapsed or refractory
        multiple myeloma who have received one to three lines of therapy
    --  As a single agent for the treatment of patients with relapsed or
        refractory multiple myeloma who have received one or more lines of
        therapy

KYPROLIS is also approved in Algeria, Argentina, Australia, Bahrain, Belarus, Brazil, Canada, Chile, Colombia, Ecuador, Egypt, European Union, Hong Kong, India, Israel, Japan, Jordan, Kuwait, Lebanon, Macao, Malaysia, Mexico, Morocco, New Zealand, Oman, Philippines, Qatar, Russia, Saudi Arabia, Singapore, S. Korea, Switzerland, Taiwan, Thailand, Turkey and United Arab Emirates.

Important U.S. KYPROLIS(®) (carfilzomib) Safety Information

Cardiac Toxicities

    --  New onset or worsening of pre-existing cardiac failure (e.g., congestive
        heart failure, pulmonary edema, decreased ejection fraction),
        restrictive cardiomyopathy, myocardial ischemia, and myocardial
        infarction including fatalities have occurred following administration
        of KYPROLIS. Some events occurred in patients with normal baseline
        ventricular function. Death due to cardiac arrest has occurred within
        one day of administration.
    --  Monitor patients for signs or symptoms of cardiac failure or ischemia.
        Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS
        for Grade 3 or 4 cardiac adverse events until recovery, and consider
        whether to restart at 1 dose level reduction based on a benefit/risk
        assessment.
    --  While adequate hydration is required prior to each dose in Cycle 1,
        monitor all patients for evidence of volume overload, especially
        patients at risk for cardiac failure. Adjust total fluid intake as
        clinically appropriate.
    --  For patients >= 75 years, the risk of cardiac failure is increased.
        Patients with New York Heart Association Class III and IV heart failure,
        recent myocardial infarction, conduction abnormalities, angina, or
        arrhythmias may be at greater risk for cardiac complications and should
        have a comprehensive medical assessment prior to starting treatment with
        KYPROLIS and remain under close follow-up with fluid management.

Acute Renal Failure

    --  Cases of acute renal failure, including some fatal renal failure events,
        and renal insufficiency adverse events (including renal failure) have
        occurred. Acute renal failure was reported more frequently in patients
        with advanced relapsed and refractory multiple myeloma who received
        KYPROLIS monotherapy. Monitor renal function with regular measurement of
        the serum creatinine and/or estimated creatinine clearance. Reduce or
        withhold dose as appropriate.

Tumor Lysis Syndrome

    --  Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have
        occurred. Patients with a high tumor burden should be considered at
        greater risk for TLS. Adequate hydration is required prior to each dose
        in Cycle 1, and in subsequent cycles as needed. Consider uric acid
        lowering drugs in patients at risk for TLS. Monitor for evidence of TLS
        during treatment and manage promptly, and withhold until resolved.

Pulmonary Toxicity

    --  Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure,
        and acute diffuse infiltrative pulmonary disease such as pneumonitis and
        interstitial lung disease have occurred. Some events have been fatal. In
        the event of drug?induced pulmonary toxicity, discontinue KYPROLIS.

Pulmonary Hypertension

    --  Pulmonary arterial hypertension (PAH) was reported. Evaluate with
        cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for
        PAH until resolved or returned to baseline and consider whether to
        restart based on a benefit/risk assessment.

Dyspnea

    --  Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea
        to exclude cardiopulmonary conditions including cardiac failure and
        pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until
        resolved or returned to baseline. Consider whether to restart based on a
        benefit/risk assessment.

Hypertension

    --  Hypertension, including hypertensive crisis and hypertensive emergency,
        has been observed, some fatal. Control hypertension prior to starting
        KYPROLIS. Monitor blood pressure regularly in all patients. If
        hypertension cannot be adequately controlled, withhold KYPROLIS and
        evaluate. Consider whether to restart based on a benefit/risk
        assessment.

Venous Thrombosis

    --  Venous thromboembolic events (including deep venous thrombosis and
        pulmonary embolism) have been observed. Thromboprophylaxis is
        recommended for patients being treated with the combination of KYPROLIS
        with dexamethasone or with lenalidomide plus dexamethasone. The
        thromboprophylaxis regimen should be based on an assessment of the
        patient's underlying risks.
    --  Patients using hormonal contraception associated with a risk of
        thrombosis should consider an alternative method of effective
        contraception during treatment.

Infusion Reactions

    --  Infusion reactions, including life?threatening reactions, have occurred.
        Symptoms include fever, chills, arthralgia, myalgia, facial flushing,
        facial edema, vomiting, weakness, shortness of breath, hypotension,
        syncope, chest tightness, or angina. These reactions can occur
        immediately following or up to 24 hours after administration.
        Premedicate with dexamethasone to reduce the incidence and severity of
        infusion reactions. Inform patients of the risk and of symptoms and seek
        immediate medical attention if they occur.

Hemorrhage

    --  Fatal or serious cases of hemorrhage have been reported. Hemorrhagic
        events have included gastrointestinal, pulmonary, and intracranial
        hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood
        loss. Reduce or withhold dose as appropriate.

Thrombocytopenia

    --  KYPROLIS causes thrombocytopenia with recovery to baseline platelet
        count usually by the start of the next cycle. Monitor platelet counts
        frequently during treatment. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

    --  Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS
        can cause increased serum transaminases. Monitor liver enzymes regularly
        regardless of baseline values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

    --  Cases of thrombotic microangiopathy, including thrombotic
        thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including
        fatal outcome have occurred. Monitor for signs and symptoms of TTP/HUS.
        Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is
        excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS
        is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

    --  Cases of PRES have occurred in patients receiving KYPROLIS. If PRES is
        suspected, discontinue and evaluate with appropriate imaging. The safety
        of reinitiating KYPROLIS is not known.

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

    --  In a clinical trial of transplant-ineligible patients with newly
        diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone
        (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence
        of serious and fatal adverse events was observed in patients in the KMP
        arm. KMP is not indicated for transplant-ineligible patients with newly
        diagnosed multiple myeloma.

Embryo-fetal Toxicity

    --  KYPROLIS can cause fetal harm when administered to a pregnant woman.
    --  Females of reproductive potential should be advised to avoid becoming
        pregnant while being treated with KYPROLIS and for 6 months following
        the final dose. Males of reproductive potential should be advised to
        avoid fathering a child while being treated with KYPROLIS and for 3
        months following the final dose. If this drug is used during pregnancy,
        or if pregnancy occurs while taking this drug, the patient should be
        apprised of the potential hazard to the fetus.

ADVERSE REACTIONS

    --  The most common adverse reactions in the combination therapy trials:
        anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia,
        pyrexia, insomnia, muscle spasm, cough, upper respiratory tract
        infection, hypokalemia.
    --  The most common adverse reactions in monotherapy trials: anemia,
        fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache,
        cough, edema peripheral

Please see full Prescribing Information at www.kyprolis.com.

About Amgen Oncology
Amgen Oncology is searching for and finding answers to incredibly complex questions that will advance care and improve lives for cancer patients and their families. Our research drives us to understand the disease in the context of the patient's life - not just their cancer journey - so they can take control of their lives.

For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company's history, moving with great speed to advance those innovations for the patients who need them.

At Amgen, we are driven by our commitment to transform the lives of cancer patients and keep them at the center of everything we do.

For more information, follow us on www.twitter.com/amgenoncology.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

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No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.

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CONTACT: Amgen, Thousand Oaks
Trish Hawkins, 805-447-5631 (media)
Jessica Akopyan, 805-447-0974 (media)
Arvind Sood, 805-447-1060 (investors)

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