|Amgen Announces Positive Top-Line Results From Phase 3 RUTHERFORD-2 Trial-(AMG 145); Avanir Announces Submission of New Drug Application for AVP-825|
|By Staff and Wire Reports|
|Thursday, 30 January 2014 20:15|
Amgen (NASDAQ: AMGN) announced that the Phase 3 RUTHERFORD-2 (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2) trial evaluating evolocumab in combination with statins and other lipid-lowering therapies in patients with heterozygous familial hypercholesterolemia (HeFH) met its co-primary endpoints: the percent reduction from baseline in low-density lipoprotein cholesterol (LDL-C) at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. The mean percent reductions in LDL-C, or "bad" cholesterol, were consistent with the results observed for the same doses in the Phase 2 RUTHERFORD trial for evolocumab compared to placebo.1
Evolocumab is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove LDL-C from the blood.2
The RUTHERFORD-2 trial evaluated safety, tolerability and efficacy of evolocumab in 329 HeFH patients on a stable dose of statin and other lipid-lowering therapies. Patients were randomized to one of four treatment groups to compare subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) with subcutaneous placebo (every two weeks or monthly).
Safety was balanced across treatment groups except for the following most common adverse events (≥ 2 percent in evolocumab combined group and ≥ 2 percent compared to placebo): nasopharyngitis (8.6 percent evolocumab; 4.6 percent placebo), contusion (4.1 percent evolocumab; 0.9 percent placebo), back pain (3.6 percent evolocumab; 0.9 percent placebo), nausea (3.6 percent evolocumab; 0.9 percent placebo), influenza (3.2 percent evolocumab; 0.0 percent placebo), and myalgia (2.7 percent evolocumab; 0.0 percent placebo).
"Data from the RUTHERFORD-2 study suggest that evolocumab, when used as an add-on therapy to existing lipid-lowering medications, may offer a new treatment option for patients with heterozygous familial hypercholesterolemia," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The RUTHERFORD-2 study is the fifth pivotal LDL-C lowering study in our Phase 3 program. The robust data from these five studies will form the basis of our global filing plan and we look forward to discussions with regulatory agencies."
Details of the Phase 3 RUTHERFORD-2 study results will be submitted to a future medical conference and for publication.
In a separate Phase 3 study that enrolled 164 patients with high cholesterol on statin therapy, 95 percent or greater of patients were able to self-administer at least one full home administration of evolocumab 420 mg subcutaneously by one injection with an automated mini-doser or by three injections with a standard spring-based autoinjector. Reductions in LDL-C were comparable with both devices and consistent to those seen in the Phase 2 LAPLACE-TIMI 57 (LDL-C Assessment with PCSK9 MonoclonaL Antibody Inhibition Combined with Statin ThErapy -Thrombolysis In Myocardial Infarction-57) trial. Safety was balanced between the treatment groups and no new safety concerns were identified.
According to the Centers for Disease Control and Prevention, more than 71 million American adults have high LDL-C.3 Elevated LDL-C is recognized as a major risk factor for cardiovascular disease.4-5 Patients with familial hypercholesterolemia, an inherited condition that causes high levels of LDL-C levels beginning at birth, are at high-risk for cardiovascular events at an early age.6 Heterozygous familial hypercholesterolemia is one of the most common genetic disorders, affecting approximately one out of every 300 to 500 people worldwide.7
RUTHERFORD-2 Study Design RUTHERFORD-2 (RedUction of LDL-C with PCSK9 InhibiTion in HEteRozygous Familial HyperchOlesteRolemia Disorder Study-2) is a Phase 3 randomized, multicenter, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability and efficacy of evolocumab in 329 patients with HeFH and an LDL-C >100 mg/dL who were on a stable dose of statin therapy and lipid-lowering medication. Patients were randomized to one of four treatment groups to compare subcutaneous evolocumab (140 mg every two weeks or 420 mg monthly) with subcutaneous placebo (every two weeks or monthly). The co-primary endpoints were the percent reduction from baseline in LDL-C at week 12 and the mean percent reduction from baseline in LDL-C at weeks 10 and 12. Co-secondary efficacy endpoints included means at weeks 10 and 12 and at week 12 for the following: absolute change from baseline in LDL-C; LDL-C < 70 mg/dL; and the percentage change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol (TC)/HDL-C ratio, ApoB/apolipoprotein A1 (ApoA1) ratio, lipoprotein(a), triglycerides, HDL-C and very low-density lipoprotein cholesterol (VLDL-C).
About PROFICIO: The Evolocumab Clinical Trial Program PROFICIO, which stands for the Program to Reduce LDL-C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different POpulations, is a large and comprehensive clinical trial program evaluating evolocumab. Phase 3 clinical trials for evolocumab are currently underway and build upon the Phase 2 studies.
The Phase 3 program includes 13 trials, with a combined planned enrollment of more than 28,000 patients. The Phase 3 studies will evaluate evolocumab administered every two weeks and monthly in multiple patient populations, including in combination with statins in patients with hyperlipidemia (LAPLACE-2), in patients with hyperlipidemia who cannot tolerate statins (GAUSS-2), as a stand-alone treatment in patients with hyperlipidemia (MENDEL-2), and in patients whose elevated cholesterol is caused by genetic disorders called heterozygous (RUTHERFORD-2) and homozygous (TESLA and TAUSSIG) familial hypercholesterolemia.
Five studies of evolocumab will provide long-term safety and efficacy data. These include FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), which will assess whether treatment with evolocumab in combination with statin therapy compared to placebo and statin therapy reduces recurrent cardiovascular events in approximately 22,500 patients with cardiovascular disease, DESCARTES (Durable Effect of PCSK9 Antibody CompARed wiTh PlacEbo Study) in patients with hyperlipidemia at risk for cardiovascular disease, and GLAGOV (GLobal Assessment of Plaque ReGression with a PCSK9 AntibOdy as Measured by IntraVascular Ultrasound), which will determine the effect of evolocumab on coronary atherosclerosis in approximately 950 patients undergoing cardiac catheterization.
Avanir Pharmaceuticals, Inc. (NASDAQ: AVNR) announced that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for approval of AVP-825, its innovative Breath Powered™ investigational drug-device combination product for the acute treatment of migraine.
The company's 505(b)(2) NDA for AVP-825 includes data from one pivotal phase III clinical trial for the acute treatment of migraine. The NDA is also supported by data from a phase II placebo-controlled clinical trial for acute treatment of migraine, and two pharmacokinetic studies. Overall, the submission includes safety data from 222 subjects who received AVP-825 in clinical trials, and references data from the extensive clinical use of sumatriptan over the past 20 years.
"The AVP-825 NDA submission represents an important milestone for Avanir," said Joao Siffert, MD, chief scientific officer at Avanir. "If approved by the FDA, AVP-825 could meet a key unmet need by providing patients with a unique device that efficiently delivers a low dose of sumatriptan powder, providing rapid relief of migraine headache, coupled with good tolerability."
About AVP-825 AVP-825 is an investigational drug-device combination product consisting of low-dose sumatriptan powder delivered intranasally utilizing a novel Breath Powered delivery technology. If approved, AVP-825 would be the first and only fast-acting, dry-powder intranasal form of sumatriptan for the treatment of migraine.
The Breath Powered delivery technology is activated by user's breath to propel medications deep into the nasal cavity where absorption is more efficient and consistent than through most other routes. A user exhales into the device, automatically closing the soft palate and sealing off the nasal cavity completely. Through a sealing nosepiece placed into the nostril, the exhaled breath carries medication from the device directly into one side of the nose. Narrow nasal passages are gently expanded and medication is dispersed deep into the nasal cavity reaching areas where it can be rapidly absorbed. As the medication is delivered, the air flows around to the opposite side of the nasal cavity and exits through the other nostril. Closure of the soft palate helps prevent swallowing or inhalation of sumatriptan powder into the lungs.
Abiomed, Inc. (Nasdaq:ABMD), a leading provider of breakthrough heart support technologies, today reported third quarter fiscal 2014 revenue of $46.2 million, up 21% compared to revenue of $38.3 million in the same period of fiscal 2013, and a third quarter fiscal 2014 GAAP net income of $4.4 million, or $0.11 per diluted share, compared to $2.7 million, or $0.07 per diluted share, in the prior year period.
Align Technology, Inc. (NASDAQ: ALGN) today announced the upcoming release of ClinCheck Pro, the next generation Invisalign treatment software tool, designed to provide more precise control over final tooth position and to help Invisalign providers achieve their treatment goals.
Amicus Therapeutics (Nasdaq:FOLD) today announced that three oral presentations and five posters highlighting its development programs for lysosomal storage diseases will be included at the 10th Annual Lysosomal Disease Network WORLD Symposium (LDN WORLD), to be held February 10-14, 2014 in San Diego, CA.
athenahealth, Inc.(Nasdaq:ATHN), a leading provider of cloud-based services for electronic health record (EHR), practice management, and care coordination, today announced that it has earned five Best in KLAS rankings within the "2013 Best in KLAS Awards: Software & Services" annual report.
Celsus Therapeutics Plc (Nasdaq:CLTX) (formerly OTCQB:CLSXD), an emerging growth, development-stage biotech company, announced today the pricing of its public offering of 1,333,333 American Depository Shares ("ADSs") on the NASDAQ Capital Market at a price of $6.00 per ADS.
Chelsea Therapeutics International, Ltd. (Nasdaq:CHTP) today announced that Keith W. Schmidt has been named Chief Commercial Officer, effective January 28, 2014. Mr. Schmidt has served as a consultant to the Company since 2012.
Medical Marijuana, Inc. (OTC Pink:MJNA) is pleased to inform shareholders and the general public that HempMedsPX™—a corporate portfolio company of Medical Marijuana, Inc. and the exclusive master distributor and contracted marketing company for CannaVest Corp. and Medical Marijuana, Inc.— has signed an agreement to exclusively supply the world's first industrial cannabidiol (CBD)-rich hemp oil-based anti-aging Cannabis Beauty DEFINED™ product line to a home-based business organization.
Novogen Limited (ASX: NRT; NASDAQ: NVGN), an oncology drug development company, today announced it will host a corporate update with Graham Kelly, Ph.D., Novogen Group Executive Chairman and Chief Executive Officer, and David Brown, Ph.D., Chief Scientific Officer on Friday, February 7, 2014 at 8:00 a.m. (Sydney local time).
Nuvilex, Inc. (OTCQB:NVLX), an international biotechnology company providing cell and gene therapy solutions for the treatment of diseases, announced today that it has received its share issuance from SGAustria Pte. Ltd. (Austrianova), who owns Austrianova Singapore Pte. Ltd. (Austrianova Singapore), that equates to a 14.5% equity interest in Austrianova.
Oculus Innovative Sciences, Inc. (Nasdaq:OCLS) today announced that the financial results for its fiscal third quarter 2014, ended December 31, 2013, will be released after the U.S. market closes on February 13, 2014.
OXiGENE, Inc. (Nasdaq:OXGN), a clinical-stage biopharmaceutical company developing novel therapeutics to treat cancer, announced that Peter Langecker, M.D., PhD., President and Chief Executive Officer, will provide a corporate overview at the 16th annual BIO CEO & Investor conference on February 11, 2014 at 11:00 am ET at the Waldorf Astoria Hotel in New York City.
PetMed Express, Inc. (Nasdaq:PETS) today announced that its Board of Directors declared a quarterly dividend of $0.17 per share on its common stock. The dividend will be payable on February 21, 2014, to shareholders of record at the close of business on February 12, 2014.
QuoteMedia, Inc. (OTCQB:QMCI) announced today a three-year agreement to provide streaming real-time portfolio management, comprehensive financial market data and research information to MD Physician Services Inc. (MD).
StemCells, Inc. (Nasdaq:STEM) announced today that Martin McGlynn will present at the following conferences: 16th Annual BIO CEO & Investor Conference in New York on February 10, 2014, at 2:30 p.m. EST; Leerink Swann 2014 Global Healthcare Conference in New York on February 12, 2014 at 3:00 p.m. EST.
Urologix®, Inc. (OTCQB:ULGX) will host a conference call to present fiscal year 2014 second quarter results on Tuesday, February 4, 2014 at 4:00 p.m. CT, following the Company's post-market press release on the same day.
Utah Medical Products, Inc. (Nasdaq:UTMD) concluded another excellent financial year in 2013 under difficult conditions.
Xenetic Biosciences, Inc. (OTCBB:GAIFD), a biopharmaceutical company developing next-generation biologic drugs and novel oncology therapeutics, today announced that it has received a direct investment of $10 million from Baxter International, Inc. and has agreed to a restructuring of certain financial and timing aspects of its existing licensing deal with Baxter.