Sanofi and MyoKardia, Inc. Announce Collaboration to Develop Targeted Therapies for Patients with Genetic Heart Disease
Sep 17 14
Sanofi and MyoKardia, Inc. announced a worldwide collaboration to discover and develop first-of-its-kind targeted therapeutics for heritable heart diseases known as cardiomyopathies, the most common forms of heart muscle disease. The collaboration builds upon MyoKardia`s pioneering science, which hopes to correct the disruptive effects that disease mutations have on heart muscle contraction. The collaboration, representing one of the research and development commitments to genetic forms of cardiomyopathy, encompasses three MyoKardia programs. Two of these programs are focused on hypertrophic cardiomyopathy (HCM) and the other is focused on dilated cardiomyopathy (DCM). The collaboration provides up to $200 million in equity investments, milestone payments and research and development services through 2018, of which $45 million has already been received in an upfront licensing fee and an initial equity investment. In addition, Sanofi and MyoKardia will equally share development costs on the HCM programs following initial demonstration of efficacy in patients, with Sanofi fully covering the development costs of the DCM program. The collaboration is an outgrowth of Sanofi`s Sunrise initiative, a strategic partnership model that seeks to invest in early stage opportunities that align with Sanofi`s expert development and commercialization abilities. The commitment of resources from Sanofi will accelerate and broaden MyoKardia`s basic disease research and will support the shared commitment of bringing desperately needed therapies to patients. Within the collaboration, MyoKardia will drive research and worldwide development activities through early human efficacy studies. Thereafter, MyoKardia will lead worldwide development and U.S. commercial activities for the two HCM programs, where it has retained product rights, and Sanofi will lead global development and commercial activities for DCM where it has obtained worldwide rights, and ex-U.S. regulatory and commercial activities to the two HCM programs where it has ex-U.S. commercialization rights. Sanofi also has the option to co-promote in the U.S. for potential expanded cardiovascular diseases outside of the genetically targeted indications for either of the HCM programs, with MyoKardia having the option to co-promote the DCM program in the U.S.
Sanofi Announces Positive Interim Results from the Second Year of the Extension Study of Lemtrada (alemtuzumab) for Multiple Sclerosis
Sep 11 14
Sanofi company announced positive interim results from the second year of the extension study of Lemtrada (alemtuzumab) for multiple sclerosis. In this analysis, relapse rates and sustained accumulation of disability remained low among patients who had previously received Lemtrada in either of the Phase III CARE-MS I and CARE-MS II studies. In these pivotal studies, Lemtrada was given as two annual courses, at the start of the study and 12 months later. Approximately 70% of patients who received Lemtrada in the pivotal studies did not receive further treatment with Lemtrada through the second year of the extension study. No new safety signals were identified. The Phase III trials of Lemtrada were randomized, two-year pivotal studies comparing treatment with Lemtrada to high-dose subcutaneous interferon beta-1a (Rebif) in patients with relapsing-remitting multiple sclerosis who had active disease and were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II). More than 90% of the patients who were treated with Lemtrada in the Phase III trials enrolled in the extension study. These patients were eligible to receive additional treatment with Lemtrada in the extension study if they experienced at least one relapse or at least two new or enlarging brain or spinal cord lesions. The following interim results are from the second year of the extension study for patients who previously received Lemtrada in the two-year pivotal studies: in year four, the annualized relapse rates for patients who received Lemtrada in CARE-MS I and CARE-MS II were 0.14 and 0.23, respectively. These rates were comparable to the annualized relapse rates for those patients who received Lemtrada in the pivotal trials. Through year four, 74% of patients in CARE-MS I and 66% in CARE-MS II had improved or stable disability as measured by the Expanded Disability Status Scale. Through year four, 83% and 76% of patients who received Lemtrada in the pivotal trials, respectively, did not experience six-month sustained accumulation of disability - meaning they did not experience a worsening of their disability that persisted for six continuous months in the four years of observation. Approximately 70% of patients treated with Lemtrada in the pivotal studies did not receive a third course of treatment in years three and four.
Regeneron Pharmaceuticals, Inc. and Sanofi Announce Presentation of Detailed Positive Results from Four Pivotal Alirocumab Trials at ESC Congress 2014
Aug 31 14
Regeneron Pharmaceuticals, Inc. and Sanofi announced detailed positive results from four Phase 3 ODYSSEY trials of alirocumab in people with hypercholesterolemia. Alirocumab is an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9). Results from the four ongoing trials, all of which met their primary efficacy endpoint, will be presented at a Hot Line session at the ESC Congress 2014 in Barcelona, Spain. ODYSSEY LONG TERM Trial: The ongoing 2,341-patient, double-blind ODYSSEY LONG TERM trial is designed to evaluate the long-term safety and efficacy of 150 milligrams (mg) alirocumab every two weeks versus placebo in patients with hypercholesterolemia who are at high or very-high cardiovascular (CV) risk, including patients with an inherited form of high cholesterol known as heterozygous familial hypercholesterolemia (HeFH). Both study groups are treated with statins at a maximally-tolerated dose and some patients also receive additional lipid-lowering therapies. A pre-specified interim analysis was performed when all patients reached one year and approximately 25% of patients reached 18 months of treatment. Key data to be presented on Aug. 31, 2014 include: On the primary efficacy endpoint of the trial, at 24 weeks, there was a 61% reduction from baseline in LDL-C levels in the alirocumab group as compared to a 1% increase in the placebo group (62% reduction in alirocumab group compared to placebo), p less than 0.0001. At 52 weeks, there was a 57% reduction from baseline in LDL-C levels in the alirocumab group as compared to a 4% increase in the placebo group (61% reduction in alirocumab group compared to placebo), p less than 0.0001. 81% of alirocumab patients achieved their pre-specified LDL-C goal (either 70 milligrams/deciliter [mg/dL] or 100 mg/dL depending on patients' baseline CV risk) compared to 9% for placebo (p less than 0.0001). The most common adverse events (greater than or equal to 5% of patients) were nasopharyngitis (13% alirocumab; 13% placebo), upper respiratory tract infection (7% alirocumab; 8% placebo), and injection site reactions (6% alirocumab; 4% placebo). In a post hoc safety analysis, there was a lower rate of adjudicated major CV events (cardiac death, myocardial infarction, stroke, and unstable angina requiring hospitalization) in the alirocumab group compared to placebo (1.4% compared to 3.0%, nominal p-value less than 0.01). These CV events comprise the composite primary endpoint of the ongoing 18,000-patient ODYSSEY OUTCOMES trial, which is prospectively evaluating the potential of alirocumab to demonstrate CV benefit. Three additional trials (ODYSSEY COMBO II, FH I and FH II) will also be presented on Aug. 31, 2014. In these three trials, alirocumab-treated patients receive an initial dose of alirocumab 75 mg every two weeks, increasing to 150 mg if needed to reach pre-specified LDL-C levels. The 75 mg and 150 mg alirocumab doses were delivered as a single, self-administered 1 milliliter (mL) injection. ODYSSEY COMBO II trial: ODYSSEY COMBO II is a double-blind, 720-patient trial designed to evaluate the safety and efficacy of alirocumab compared to ezetimibe in patients with hypercholesterolemia who are at high CV risk and had inadequate LDL-C reduction at baseline despite stable maximally-tolerated statin therapy. Key data to be presented on Aug. 31, 2014 include: On the primary endpoint of the trial, at 24 weeks, there was a 51% reduction from baseline in LDL-C levels in the alirocumab group compared to a 21% reduction in the ezetimibe group (30% reduction in alirocumab group compared to ezetimibe group), p less than 0.0001. At 52 weeks, there was a 50% reduction from baseline in LDL-C levels in the alirocumab group compared to an 18% reduction in the ezetimibe group (32% reduction in alirocumab group compared to ezetimibe group), p less than 0.0001. 77% of patients in the alirocumab group achieved an LDL-C level of 70 mg/dL at 24 weeks. Approximately 80% of patients in the alirocumab group remained on the initial 75 mg alirocumab dose. The most common adverse events (greater than or equal to 5% of patients) were upper respiratory tract infection (6.5% alirocumab; 6% ezetimibe), accidental overdose (6% alirocumab; 7% ezetimibe), dizziness (5% alirocumab; 5% ezetimibe), and myalgia (4% alirocumab; 5% ezetimibe). ODYSSEY FH I and FH II trials: The ODYSSEY FH I and FH II trials enrolled a total of 738 HeFH patients and compare alirocumab to placebo. All patients are on maximally-tolerated daily statin therapy and the majority of patients also receive ezetimibe. Despite receiving this high level of background therapy, patients in these studies had mean baseline LDL-C levels of 145 mg/dL (FH I) and 134 mg/dL (FH II).