Amgen Receives FDA Approval on Corlanor (Ivabradine) to Reduce the Risk of Hospitalization for Worsening Heart Failure in Patients with Chronic Heart Failure
Apr 16 15
Amgen announced that the U.S. Food and Drug Administration (FDA) has granted approval of Corlanor (ivabradine), an oral medication indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure with left ventricular ejection fraction (LVEF) =35%, who are in sinus rhythm with resting heart rate =70 beats per minute (bpm) and either are on maximally tolerated doses of beta blockers or have a contraindication to beta blocker use. Corlanor blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. Corlanor reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current ('funny' current) to slow the heart rate with no effect on ventricular repolarization and no effects on myocardial contractility. The Corlanor approval is based on global clinical trial data including a large, multicenter, randomized, double-blind, placebo-controlled, outcomes trial. The Phase 3 SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) study compared Corlanor to placebo on top of standard of care (SOC) therapies, including beta blockers, in more than 6,500 clinically stable (=4 weeks) patients in sinus rhythm with reduced left ventricular function (LVEF =35%) and heart rate =70 bpm, with a hospitalization for heart failure within the past 12 months. Patients received SOC, including beta blockers (89%), angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II receptor blockers (ARB) (91%), diuretics (83%) and anti-aldosterone agents (60%). Results from the Phase 3 SHIFT study showed Corlanor significantly reduced the risk of the primary composite endpoint of hospitalization or cardiovascular death for worsening heart failure, with 18% relative risk reduction (RRR) pAbout Corlanor® (ivabradine) Corlanor blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker, which regulates heart rate. Corlanor reduces the spontaneous pacemaker activity of the cardiac sinus node by selectively inhibiting the If current ('funny' current) to slow the heart rate with no effect on ventricular repolarization and no effects on myocardial contractility.5 Corlanor was developed by Les Laboratoires Servier. Through a collaboration with Servier, Amgen has rights to commercialize Corlanor in the U.S.
European Commission Approves Amgen's Vectibix® (panitumumab) as First-Line Treatment With FOLFIRI Chemotherapy for Metastatic Colorectal Cancer
Apr 6 15
Amgen Inc. announced that the European Commission approved a new use of Vectibix® (panitumumab) as first-line treatment in combination with FOLFIRI for the treatment of adult patients with wild-type (WT) RAS metastatic colorectal cancer (mCRC). About half of the patients with mCRC have WT RAS tumors. FOLFIRI, an irinotecan-based chemotherapy regimen, is frequently used in first-line colorectal cancer treatment in Europe. The new indication is based upon studies that evaluated Vectibix plus FOLFIRI in the first-line setting. Vectibix is now approved in the European Union (EU) for the treatment of adult patients with WT RAS mCRC: in first-line in combination with FOLFOX or FOLFIRI; in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based chemotherapy (excluding irinotecan); and as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Colorectal cancer is the third most common cancer worldwide, with approximately 1.2 million cases expected to occur globally. Colorectal cancer is the second most common cancer in Europe, with approximately 470,000 new cases each year; the high incidence rate of colorectal cancer in the world. It is also the second great cause of cancer death in Europe following lung cancer, accounting for 12% of all cancer deaths. In the EU, Vectibix is currently indicated for the treatment of adult patients with wild-type RAS mCRC:in first-line in combination with FOLFOX and FOLFIRI.; in second-line in combination with FOLFIRI for patients who have received first-line fluoropyrimidine-based;chemotherapy (excluding irinotecan).; as monotherapy after failure of fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy; regimens.Dermatologic related reactions, a pharmacologic effect observed with epidermal growth factor receptor (EGFr) inhibitors, are experienced with nearly all patients (approximately 90%) treated with Vectibix. The majority of dermatological reactions are mild to moderate in nature. In clinical studies, subsequent to the development of severe dermatological reactions (including stomatitis), infectious complications including sepsis, in rare cases leading to death, and local abscesses requiring incisions and drainage were reported. Patientswho have severe dermatologic reactions or who develop worsening reactions whilst receiving Vectibix should be monitored for the development of inflammatory or infectious sequelae, and appropriate treatment promptly initiated. Vectibix is indicated for the treatment of patients with wild-type KRAS (exon 2 in codons 12 or 13) metastatic colorectal cancer (mCRC) as determined by an FDA-approved test for this use:As first-line therapy in combination with FOLFOX· As monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing emotherapy. Vectibix is not indicated for the treatment of patients with RAS-mutant mCRC or for whom RAS mutation status is unknown. Dermatologic Toxicity: Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 or higher) in 15% of patients receiving Vectibix monotherapy.Vectibix is not indicated for the treatment of patients with colorectal cancer that harbor somatic mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS". Additionally, in Study 3, 272 patients with RAS-mutant mCRC tumors received Vectibix in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI 1.01-1.45) in patients with RAS-muta t mCRC who received Vectibix and FOLFOX versus FOLFOX alone. Progressively decreasing serum magnesium levels leading to severe (Grade 3-4) hypomagnesemia occurred in up to 7% (in Study 2) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix treatment, periodically during Vectibix treatment, and for up to 8 weeks after the completion of treatment. In Study 1, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix in combination with chemotherapy. Fatal and non-fatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled inclinical studies of Vectibix. In the event of acute onset or worsening of pulmonary symptoms, interruptVectibix therapy. Discontinue Vectibix therapy if ILD is confirmed. The most common adverse reactions (> 20%) of Vectibix are skin rash with variable presentations, paronychia, fatigue, nausea and diarrhea. The most frequently reported adverse reactions for Vectibix leading to withdrawal were general physical health deterioration and intestinal obstruction. The most commonly reported adverse reactions (= 20%) in patients with wild-type KRAS mCRC receiving Vectibix (6 mg/kg every 2 weeks) and FOLFOX therapy (N = 322) in Study 3 were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. Serious adverse reactions (= 2% difference between treatment arms) in Vectibix-treated patients with wild-type KRAS mCRC were diarrhea and dehydration.
US FDA Accepts Amgen Priority Review for Kyprolis (Carfilzomib) Supplemental New Drug Application for the Treatment of Relapsed Multiple Myeloma
Mar 30 15
Amgen Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental New Drug Application (sNDA) of Kyprolis® (carfilzomib) for Injection for the treatment of patients with relapsed multiple myeloma who have received at least one prior therapy. The sNDA is designed to support the conversion of accelerated approval to full approval and expand the current Kyprolis indication. As part of the acceptance, the FDA granted Kyprolis priority review with a Prescription Drug User Fee Act (PDUFA) target action date of July 26, 2015. The sNDA is based on data from the Phase 3 ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) trial and other relevant data. Priority review is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions. Kyprolis is currently approved by the FDA for the treatment of patients with multiple myeloma who have received at least two prior therapies, including bortezomib and an immunomodulatory agent (IMiD), and have demonstrated disease progression on or within 60 days of completion of the last therapy.