Costello Syndrome

Sept. 30, 2021 11:30 UTC PASADENA, Calif.--(BUSINESS WIRE)-- Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) today announced that it has dosed the first patient in AROAPOC3-2002, a Phase 2b clinical study of ARO-APOC3 in adults with mixed dyslipidemia. ARO-APOC3 is the company’s investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with severe hypertriglyceridemia (SHTG), mixed dyslipidemia, and familial chylomicronemia syndrome (FCS). Arrowhead intends to initiate a Phase 3 study of ARO-APOC3 in patients with FCS in the fourth quarter of 2021. Javier San Martin, M.D., chief medical officer at Arrowhead, said: “AROAPOC3-2002 is the second of three clinical trials that we plan to initiate this year to study investigational ARO-APOC3 in various patient populations, each with a unique lipid profile. The ‘2001 study, which we initiated in June of 2021, is enrolling patients with severe hypertriglyceridemia. The ‘2002 study is enrolling patients with mixed dyslipidemia, defined by moderately elevated triglycerides and elevated non-high-density lipoprotein cholesterol or elevated low-density lipoprotein cholesterol at screening. The planned ‘3001 study, which is on track to begin in the fourth quarter of 2021, will be a Phase 3 study in patients with genetically defined FCS. We look forward to continued progress for the clinical program and, if successful, providing new potential treatment options for patients with various levels of hypertriglyceridemia.” AROAPOC3-2002 (NCT04998201) is a double-blind, placebo-controlled Phase 2b study to evaluate the efficacy and safety of ARO-APOC3 in adults with mixed dyslipidemia. Four dose cohorts of ARO-APOC3 will be evaluated against placebo in participants who had the following at screening: (i) elevated triglycerides (TG) greater than or equal to 150 mg/dL (1.69 mmol/L) but less than 499 mg/dL (5.61 mmol/L), and (ii) non-high-density lipoprotein cholesterol (non-HDL-C) greater than or equal to 100 mg/dL (2.59 mmol/L) or low-density lipoprotein cholesterol (LDL-C) greater than or equal to 70 mg/dL (1.8 mmol/L) at screening. A total of approximately 320 participants will be enrolled in the study. All dose cohorts will enroll in parallel with approximately 80 participants per dose cohort, randomly assigned in a 3:1 ratio to receive ARO-APOC3 or placebo. In three cohorts (10 mg, 25 mg, 50 mg), each participant will receive a subcutaneous injection on day 1 and week 12 for a total of 2 injections. In one additional 50 mg cohort, each participant will receive a subcutaneous injection on day 1 and week 24 for a total of 2 injections. The duration of the study is approximately 54 weeks from screening to the week 48 end-of-study examination. The primary objective of the study is to evaluate the safety and efficacy of ARO-APOC3 in adults with mixed dyslipidemia and to select a dose and dosing regimen for later stage clinical studies in this patient population. About Arrowhead Pharmaceuticals Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. 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Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the continuing impact of the COVID-19 pandemic, the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances. Source: Arrowhead Pharmaceuticals, Inc.

lev radin/Shutterstock Findings from a recent Phase II trial show Regeneron’s monoclonal antibody evinacumab significantly reduced fasting triglycerides in patients with severe hypertriglyceridemia. Still, these findings were not replicated in a subgroup of patients with rare familial chylomicronemia syndrome (FCS). The data from the study were presented during a late-breaking clinical trial session held Sunday at the American College of Cardiology 2021 Scientific Session. Study investigator Robert Rosenson, MD, of the Icahn School of Medicine at Mount Sinai in New York, presented the data during the meeting. Dr. Rosenson noted the findings hold important clinical implications, given patients with severe hypertriglyceridemia experience chronic abdominal pain, have to adhere to a strict low-fat diet, and experience acute pancreatitis that increases their risk for other health conditions. Evinacumab, a fully human monoclonal antibody and angiopoietin-like protein 3 inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in February as an adjunct LDL cholesterol-lowering treatment for homozygous familial hypercholesterolemia (HoFH). This approval was made based on data published in 2020 that showed the agent significantly reduced cholesterol without increasing the risk of severe side effects. But in the new study, researchers examined the effects of the therapy in 51 patients with severe triglyceridemia who were using diet and maximally tolerated lipid-lowering treatments. All patients in this study were stratified by genotype. After stratification, study participants were randomly assigned to either intravenous evinacumab at 15 mg/kg every four weeks or a placebo for the initial double-blind treatment phase. After the double-blind period, all patients then received evinacumab for 12 weeks. Participants were followed for another 20 weeks to examine safety outcomes. At baseline, the median fasting triglycerides across the overall sample ranged between 1,000 and 3,000 mg/dL. After the double-blind and single-blind treatment periods, the mean reduction in triglycerides from baseline was 27.1% in the cohort of patients with multifactorial chylomicronemia syndrome (MCS) without LPL pathway mutations. The investigators observed significant reductions in the median triglyceride levels during the initial double-blind period with evinacumab compared with placebo in patients with MCS with known heterozygous loss-of-function mutations in APOA5, APOC2, GPIHBP1, LMF1, or LPL (-64.8% vs. 9.4%, respectively; p=0.0076). A similar clinically meaningful finding was reported in patients with MCS without LPL pathway mutations (-81.7% vs. 80.9%; p=0.0418). Over the 12 weeks, the same groups of patients experienced marked reductions in non-HDL-cholesterol, Apo-CIII, and ApoB48. Despite the promising efficacy, the researchers did not observe clinically meaningful reductions in mean triglycerides for patients with FCS who had bi-allelic loss-of-function mutations in APOA5, APOC2, GPIHBP1, LMF1, or LPL. A similar proportion of patients in the evinacumab and placebo arms experienced treatment-emergent adverse events throughout the study (71.4% vs. 68.8%, respectively). A proportionally lower number of serious adverse events were reported in the active treatment arm (11.4%) vs the placebo group (18.8%). A total of two cases of acute pancreatitis were reported in the placebo group, while three cases were reported in the evinacumab-treated patients. Regeneron currently has planned a Phase IIb study that will examine intravenous evinacumab at 20 mg/kg every four weeks for the treatment of acute pancreatitis. Featured Jobs on BioSpace

Western pharmaceutical companies continue to forge strong relationships with Chinese companies in order to gain inroads into that increasingly important market. This week, U.K.-based Oxford BioTherapeutics struck a deal with Wuxi Biologics for a second bispecific program that will combine an anti-PD-L1 antibody with OBT’s immuno-oncology (IO) candidate, OX003. OBT will research and develop OX003/PD-L1, which employs WuXi Biologics’ proprietary bispecific antibody platform WuXiBody. Christian Rohlff, chief executive officer of Oxford BioTherapeutics, said the new deal represents an advancement with WuXi that will allow the company to research, develop and commercialize five novel bispecific antibodies for the treatment of several cancer types. “Combining the potent immune stimulatory activity of OX003 with the ability to block PD-L1 in a single agent, OX003/PD-L1 has the potential to achieve broad utility across many solid and liquid tumor types while simultaneously improving the risk/benefit ratio, reducing costs and maximizing future commercial potential. This product is the second molecule with WuXiBody in our partnership, following the design of OX001/PD-L1, which is now entering pre-clinical development,” Rohlff said in a statement. Elsewhere across the globe: Metrion Biosciences – U.K.-based Metrion Biosciences Limited and LifeArc, a UK independent medical research charity, today announced a 12-month extension of their neuroscience drug discovery collaboration, as a result of the continued success of their ongoing agreement. The collaboration is focused on the discovery of novel selective small molecular modulators of a specific two-pore domain potassium ion channel target. Under the terms of the agreement, Metrion provides validated ion channel and electrophysiology-based assays and safety profiling services. LifeArc uses its expertise to identify novel modulators of CNS ion channel targets and all new chemical syntheses, with Metrion evaluating the pharmacological activities of LifeArc compounds using both automated electrophysiology and manual patch clamp technologies. Biophytis – Based in France, Biophytis SA announced the recommendation by the DMC to start recruitment for the second part of the Phase II/III COVA study. The COVA Study assesses Sarconeos (BIO101) as a potential treatment for acute respiratory failure associated with COVID-19. The COVA clinical program is a global, multicentric, double-blind, placebo-controlled, group-sequential, and adaptive design two-part Phase 2-3 study assessing Sarconeos (BIO101) in patients aged 45 and older, hospitalized with severe respiratory manifestations of COVID-19. Results from the full study are expected in the second quarter of this year, subject to any COVID-19 related delays and the impact of the current pandemic. Owlstone Medical – U.K.-based Owlstone Medical introduced the Respiratory Diseases Research Use Only (RUO) Panel. The breath biomarker panel, which is now commercially available, is intended to support research to distinguish between different types of chronic inflammatory airway diseases including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), and to facilitate better therapeutic decision making and monitoring. Owlstone Medical’s Respiratory Diseases RUO Panel consists of a set of biologically relevant Volatile Organic Compounds (VOCs) that have been linked to inflammatory respiratory diseases, and can be easily collected on breath to enable direct characterization of disease biology in the lungs by non-invasively sampling the airways. Optibrium – Also based in the U.K., Optibrium, which developed software for drug discovery, announced the release of its newest version of StarDrop, a comprehensive software platform for small molecule design, optimization and data analysis. The new release, StarDrop 7.0, extends the software’s compound design strategies, provides enhanced workflows, and seamlessly connects with Optibrium’s Cerella platform, delivering unique Artificial Intelligence (AI) capabilities to drug discovery scientists, the company said. Lytix Biopharma – Norway-based Lytix Biopharma AS received clearance from the U.S. Food and Drug Administration to initiate a Phase II clinical trial is designed to assess the efficacy of its lead candidate LTX-315, a first-in-class oncolytic peptide, in several solid tumor types. The IND approval enables Lytix to conduct a Phase II clinical trial designed to assess the efficacy of LTX-315 in several types of solid tumors including metastatic breast cancer and head and neck squamous cell carcinoma. Lytix Biopharma develops the drug candidate LTX-315 for several types of cancer. In August, Lytix entered into an exclusive worldwide license agreement with Verrica Pharmaceuticals to develop and commercialize LTX-315 for dermatologic oncology indications. Lytix`s IND approval is for other cancer indications, but it triggers a significant milestone payment to Lytix according to the licensing agreement. Calyx – Based in the U.K, Calyx announced its Medical Imaging and other eClinical solutions supported half of the oncology treatments approved by the FDA as Breakthrough Therapies in the past two years. Calyx’s eClinical solutions include Medical Imaging, Interactive Response Technology, Regulatory Information Management, Clinical Trial Management, and Electronic Data Capture. Cellink – Sweden’s Cellink and U.K.-based Phasefocus announced a partnership to bring Livecyte, a high content live cell imager, to a wider market. Livecyte’s integration of the patented label-free Quantitative Phase Imaging technology with state-of-the-art automatic cell tracking algorithms enables users to automatically characterize growth, morphology and motility of large populations of cells in a 96-well plate assay format. Combining Cellink’s already extensive product portfolio of bioprinters, liquid handlers and bioinks with Livecyte offers researchers a unique opportunity to improve workflow efficiencies in application areas such as drug discovery, regenerative medicine and cell-based assays. Secarna – Germany’s Secarna Pharmaceutical GmbH & Co. announced that the company’s partner Lipigon Pharmaceuticals AB has selected the candidate drug Lipisense to treat elevated levels of plasma lipid triglycerides. The candidate is being developed for patients suffering from severe hypertriglyceridemia as well as the rare disease Familial Chylomicronemia Syndrome (FCS), diseases that may lead to painful and potentially life-threatening syndrome acute pancreatitis. Lipisense, an antisense oligonucleotide (ASO) which has been developed with Secarna’s proprietary LNAplus platform, is a first-in-class treatment with a novel mechanism of action central for the regulation of plasma triglycerides and other plasma lipids. The drug candidate hinders the cellular production of ANGPTL4, a protein that has a direct role in lipid metabolism by blocking the clearance of triglycerides. The protein has been associated with tumor progression and has shown a strong genetical validation and correlation with harmful plasma lipids and the associated diseases. Exact Therapeutics – Based in Norway, Exact Therapeutics AS announced a collaboration with GE Healthcare to develop an innovative ultrasound probe to be used in forthcoming studies using Acoustic Cluster Therapy (ACT) across multiple disease conditions. ACT is a proprietary formulation consisting of microbubbles and microdroplets that are activated through the application of ultrasound with the consequent increase in targeted delivery of a co-administered therapeutic agent. NAC – The Native Antigen Company, based in the U.K. announced the introduction of its new range of veterinary reagents. The company’s offering includes over 90 high-quality native and recombinant antigens, and monoclonal and polyclonal antibodies for a range of viral, bacterial and protozoal veterinary diseases, that can be used in the development of diagnostics and vaccines. The company’s reagents have been developed for both livestock and companion animals.