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A new study suggests that to optimize neuroprotection and prevent cerebral palsy in extremely preterm infants, women should receive magnesium sulfate to obtain a blood level between 3.7 and 4.4 mg/dL at the time of delivery. The study included 636 women who received magnesium sulfate and 1269 who received placebo. The findings are important because magnesium sulfate is indicated for neuroprotection of preterm fetuses; however, the optimal dosing schedule to prevent cerebral palsy is not known. "Women have traditionally received a standard dose of magnesium sulfate to prevent cerebral palsy in the extremely preterm fetus, but this study is the first to use pharmacokinetic modeling to suggest a therapeutic target maternal serum level we should aim for," said Dr. Kathleen Brookfield, lead author of the Journal of Clinical Pharmacology study. "The dose of magnesium sulfate can now be tailored depending on maternal factors and the clinical situation to achieve this target."


A vaccine to immunize people against high levels of cholesterol and the narrowing of the arteries caused by build-up of fatty material (atherosclerosis) may be possible following successful results in mice. Now, a phase I trial in patients has started to see if the findings translate to humans. The study, which is published in the European Heart Journal, is the first to show that it is possible to immunize genetically modified mice with a molecule that causes the body to produce antibodies against an enzyme called PCSK9 (Proprotein covertase subtilisin/kexin type 9), which plays a role in preventing the clearance of low density lipoprotein cholesterol ("bad" cholesterol) from the blood. People with high levels of LDL cholesterol, either due to their genetic inheritance, or to poor diet and lifestyles, are at much greater risk of developing cardiovascular disease prematurely. These diseases of the heart and blood vessels, caused by atherosclerosis, have overtaken infections as the main cause of illness and death throughout the world. At present, drugs such as statins can be used to lower LDL cholesterol, but they have to be taken on a daily basis and although they are generally well-tolerated they can cause adverse side effects in some people. The most recently approved cholesterol-lowering compounds are monoclonal antibodies targeting PCSK9, which are highly effective, but their effect is short-lived, resulting in frequent re-application and high costs. The research published today shows that the AT04A vaccine, when injected under the skin in mice that have been fed fatty, Western-style food in order to induce high cholesterol and the development of atherosclerosis, reduced the total amount of cholesterol by 53%, shrank atherosclerotic damage to blood vessels by 64%, and reduced biological markers of blood vessel inflammation by 21-28%, compared to unvaccinated mice. Furthermore, the induced antibodies remained functional over the whole study period and concentrations were still high at the end of the study. Dr Günther Staffler, chief technology officer at AFFiRis (the company that developed AT04A) and one of the authors of the study, said: "AT04A was able to induce antibodies that specifically targeted the enzyme PCSK9 throughout the study period in the circulation of the treated mice. As a consequence, levels of cholesterol were reduced in a consistent and long-lasting way, resulting in a reduction of fatty deposits in the arteries and atherosclerotic damage, as well as reduced arterial wall inflammation. "The reduction in total cholesterol levels was significantly correlated with induced antibody concentration, proving that induced antibodies caused the reduction in cholesterol and also are ultimately responsible for the reduction of atherosclerosis development. As antibody concentrations remained high at the end of the study, it can be assumed they would continue to reduce cholesterol levels for some time afterwards, resulting in a long-lasting effect, as has been shown in previous studies. "If these findings translate successfully into humans, this could mean that, as the induced antibodies persist for months after a vaccination, we could develop a long-lasting therapy that, after the first vaccination, just needs an annual booster. This would result in an effective and more convenient treatment for patients, as well as higher patient compliance." The enzyme PCSK9 is made in the liver and it locks on to LDL cholesterol receptors, reducing their ability to get rid of LDL cholesterol from the blood. When injected, AT04A causes the body to produce antibodies that block the function of PCSK9, so that the activity of the LDL cholesterol receptors is increased. "The way that AT04A is administered is comparable to a vaccine," explained Dr Staffler. "However, the difference between a conventional vaccine and our approach is that a vaccine induces antibodies that are specific to bacterial or viral proteins that are foreign to the body -- pathogens -- whereas AT04A induces antibodies against a target protein that is produced by the body -- endogenous proteins. This it is really an immunotherapeutic approach rather than a vaccine approach." In 2015, a phase I clinical study started at the Department of Clinical Pharmacology, Medical University of Vienna, Austria, studying AT04A and another molecule AT06A in 72 healthy people to assess its safety and activity. The study is expected to complete at the end of this year. In an accompanying editorial, Professor Ulrich Laufs, of Saarland University, Germany, and Professor Brian Ference, of the University of Bristol, UK, and the Wayne State University School of Medicine, Detroit, USA, write: "It appears promising to further evaluate long-term LDL cholesterol lowering by vaccination against PCSK9 for the prevention of atherosclerotic events." However, they say that "safety, the response in humans and the very important but unknown long-term immune effects need to be very carefully addressed during the course of clinical development." In particular, reductions in total cholesterol via statins and other drugs are associated with an increase in new onset diabetes. "Therefore, one potential safety concern for long-term lowering of LDL cholesterol with a vaccine directed against PCSK9 is the potential for an increased risk of new onset diabetes. In the short term, the LDL cholesterol lowering effect of statins and PCS9 inhibitors appears to far outweigh the risks of new onset diabetes."


News Article | June 7, 2017
Site: www.eurekalert.org

A new analysis suggests that among older adults who take cardiovascular medications, those using non-selective beta-blockers may be at an increased of falling compared with those using selective beta-blockers. These types of drugs are already known to differ by their receptor binding properties and their systemic effects on the body. In the analysis of data from 2 prospective studies involving more than 10,000 individuals, use of a selective beta-blocker was not associated with fall risk, but use of a non-selective beta-blocker was associated with a 22% increased risk. In total, 2,917 participants encountered a fall during follow-up. The results indicate that fall risk should be considered when weighing the pros and cons of prescribing different beta-blocker classes for older individuals. "Drug-related falls remain under-recognized, leading to preventable falls and related injury. Precise prediction of drug-related fall risk is of major importance for clinical decision-making," said Dr. Nathalie van der Velde, senior author of the British Journal of Clinical Pharmacology study. "Knowledge of type-specific effects such as selectivity in beta-blockers can be expected to improve decision-making."


A vaccine to immunise people against high levels of cholesterol and the narrowing of the arteries caused by build-up of fatty material (atherosclerosis) may be possible following successful results in mice. Now, a phase I trial in patients has started to see if the findings translate to humans. The study, which is published today (Tuesday) in the European Heart Journal [1], is the first to show that it is possible to immunise genetically modified mice with a molecule that causes the body to produce antibodies against an enzyme called PCSK9 (Proprotein covertase subtilisin/kexin type 9), which plays a role in preventing the clearance of low density lipoprotein cholesterol ("bad" cholesterol) from the blood. People with high levels of LDL cholesterol, either due to their genetic inheritance, or to poor diet and lifestyles, are at much greater risk of developing cardiovascular disease prematurely. These diseases of the heart and blood vessels, caused by atherosclerosis, have overtaken infections as the main cause of illness and death throughout the world. At present, drugs such as statins can be used to lower LDL cholesterol, but they have to be taken on a daily basis and although they are generally well-tolerated they can cause adverse side effects in some people. The most recently approved cholesterol-lowering compounds are monoclonal antibodies targeting PCSK9, which are highly effective, but their effect is short-lived, resulting in frequent re-application and high costs. The research published today shows that the AT04A vaccine, when injected under the skin in mice that have been fed fatty, Western-style food in order to induce high cholesterol and the development of atherosclerosis, reduced the total amount of cholesterol by 53%, shrank atherosclerotic damage to blood vessels by 64%, and reduced biological markers of blood vessel inflammation by 21-28%, compared to unvaccinated mice. Furthermore, the induced antibodies remained functional over the whole study period and concentrations were still high at the end of the study. Dr Günther Staffler, chief technology officer at AFFiRis (the company that developed AT04A) and one of the authors of the study, said: "AT04A was able to induce antibodies that specifically targeted the enzyme PCSK9 throughout the study period in the circulation of the treated mice. As a consequence, levels of cholesterol were reduced in a consistent and long-lasting way, resulting in a reduction of fatty deposits in the arteries and atherosclerotic damage, as well as reduced arterial wall inflammation. "The reduction in total cholesterol levels was significantly correlated with induced antibody concentration, proving that induced antibodies caused the reduction in cholesterol and also are ultimately responsible for the reduction of atherosclerosis development. As antibody concentrations remained high at the end of the study, it can be assumed they would continue to reduce cholesterol levels for some time afterwards, resulting in a long-lasting effect, as has been shown in previous studies. "If these findings translate successfully into humans, this could mean that, as the induced antibodies persist for months after a vaccination, we could develop a long-lasting therapy that, after the first vaccination, just needs an annual booster. This would result in an effective and more convenient treatment for patients, as well as higher patient compliance." The enzyme PCSK9 is made in the liver and it locks on to LDL cholesterol receptors, reducing their ability to get rid of LDL cholesterol from the blood. When injected, AT04A causes the body to produce antibodies that block the function of PCSK9, so that the activity of the LDL cholesterol receptors is increased. "The way that AT04A is administered is comparable to a vaccine," explained Dr Staffler. "However, the difference between a conventional vaccine and our approach is that a vaccine induces antibodies that are specific to bacterial or viral proteins that are foreign to the body - pathogens - whereas AT04A induces antibodies against a target protein that is produced by the body - endogenous proteins. This it is really an immunotherapeutic approach rather than a vaccine approach." In 2015, a phase I clinical study [2] started at the Department of Clinical Pharmacology, Medical University of Vienna, Austria, studying AT04A and another molecule AT06A in 72 healthy people to assess its safety and activity. The study is expected to complete at the end of this year. In an accompanying editorial [3], Professor Ulrich Laufs, of Saarland University, Germany, and Professor Brian Ference, of the University of Bristol, UK, and the Wayne State University School of Medicine, Detroit, USA, write: "It appears promising to further evaluate long-term LDL cholesterol lowering by vaccination against PCSK9 for the prevention of atherosclerotic events." However, they say that "safety, the response in humans and the very important but unknown long-term immune effects need to be very carefully addressed during the course of clinical development". In particular, reductions in total cholesterol via statins and other drugs are associated with an increase in new onset diabetes. "Therefore, one potential safety concern for long-term lowering of LDL cholesterol with a vaccine directed against PCSK9 is the potential for an increased risk of new onset diabetes. In the short term, the LDL cholesterol lowering effect of statins and PCS9 inhibitors appears to far outweigh the risks of new onset diabetes." [1] "The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE*3Leiden. CETP mice", by Christine Landlinger et al. European Heart Journal. doi:10.1093/eurheartj/ehx260. [2] Study Assessing Safety, Immunogenicity and LDLc -Lowering Activity of 2 PCSK9 Targeting AFFITOPE Vaccines in Healthy Subjects (AFF012)". [3] "Vaccination to prevent atherosclerotic cardiovascular disease", by Ulirich Laufs and Brian Ference. European Heart Journal. doi:10.1093/eurheartj/ehx302


"The Dose Escalation Phase of our monotherapy study for SRA737 employs an accelerated titration design which has allowed us to rapidly and efficiently advance through several 100% dose escalations with single patient cohorts," said Dr. Barbara Klencke, Chief Development Officer of Sierra Oncology. "We have not yet observed any dose limiting toxicity and are achieving excellent exposure with several cohorts having surpassed the proposed minimum efficacious plasma concentration for SRA737 based on preclinical modelling. This has enabled the commencement of the parallel Cohort Expansion Phase of the study, described in detail in one of our posters presented at ASCO today. This innovative clinical trial design will enroll prospectively-selected genetically-defined patients into five indication-specific cohort expansions at potentially active dose levels." The SRA737 Phase 1 monotherapy trial has advanced through six single patient dose cohorts of 20, 40, 80, 160, 300 and 600 mg/day, administered under a continuous daily oral dosing regimen in 28-day cycles. Dose escalation will continue until a maximum tolerated dose (MTD) is reached, in parallel with ongoing Cohort Expansion enrollment. Preliminary observations from the ongoing monotherapy study are as follows: Having successfully surpassed the proposed minimum efficacious exposure threshold, the Cohort Expansion Phase of the trial has commenced and is enrolling patients with tumors identified to have genetic aberrations hypothesized to confer sensitivity to Chk1 inhibition via synthetic lethality into five indication-specific cohorts: colorectal, head and neck, non-small cell lung, ovarian, and prostate cancers. For the Phase 1 Chemotherapy Combination study, Stage 1, which is evaluating SRA737 in combination with gemcitabine and cisplatin, has concluded enrolment and the study has transitioned to Stage 2. This stage is seeking to establish the safety profile, determine the MTD and to propose a recommended dose for further development of SRA737 in combination with low-dose gemcitabine. Once an MTD and dosing schedule have been determined, the study will also evaluate the preliminary efficacy of SRA737 in combination with low-dose gemcitabine in indication-specific cohorts of prospectively-selected, genetically-defined subjects with bladder or pancreatic cancer. "In addition to advancing our novel synthetic lethality-oriented monotherapy study, we are also excited by the potential for SRA737 to combine synergistically with other agents. Gemcitabine is a potent inducer of replication stress and DNA damage via multiple mechanisms, and represents a rational drug combination for SRA737, given Chk1's fundamental biological role in responding to such stressors. Our preclinical modeling demonstrates robust synergistic anti-tumor activity of SRA737 in combination with low-dose gemcitabine," added Dr. Nick Glover, President and CEO of Sierra Oncology. "We expect to accrue a solid understanding of dose, schedule, pharmacodynamic and pharmacokinetic parameters for SRA737 from these two studies, and the data observed to date are encouraging and consistent with our preclinical research. Our SRA737 development program remains on track and we expect to provide an update from these studies, including potential preliminary activity data, in early 2018." About SRA737 SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of important cell cycle checkpoints and a central mediator of the DDR network. In cancer cells, replication stress induced by oncogenes (e.g., MYC or RAS) or genetic mutations in DNA repair machinery (e.g., BRCA1 or FA) combined with loss of function in tumor suppressors (e.g., TP53 or ATM) results in persistent DNA damage and genomic instability leading to an increased dependency on Chk1 for survival. Targeted inhibition by SRA737 may therefore be synthetically lethal to these cancer cells and have utility as a monotherapy in a range of tumor indications. Profound mechanistic potentiation has also been reported when Chk1 inhibition is combined with DNA damaging cytotoxic agents or radiation. The widely-used chemotherapy gemcitabine is a strong exogenous inducer of replication stress and preclinical modeling demonstrates robust synergistic anti-tumor activity for SRA737 potentiated by gemcitabine. SRA737 was discovered and initially developed at the Cancer Research UK (CRUK) Cancer Therapeutics Unit at the Institute of Cancer Research (ICR). About the SRA737 Monotherapy Trial Design This first-in-human, multicenter, Phase 1 Monotherapy study consists of two phases, a Dose Escalation Phase and a Cohort Expansion Phase, being run concurrently. The Dose Escalation Phase of the SRA737 Phase 1 monotherapy trial is investigating the safety and tolerability of SRA737 and seeking to identify its optimal dose, schedule, and maximum tolerated dose (MTD). Single patient cohorts will receive escalating doses of SRA737, starting at 20 mg, administered orally on a continuous daily dosing schedule in 28-day cycles until SRA737-related Grade 2 toxicity is observed in a dose escalation subject during Cycle 1. At that point, that dose level and all subsequent dose level cohorts will be expanded to three to six subjects, following a rolling six design. Intensive PK and pharmacodynamic assessments will be obtained on all subjects. In the Cohort Expansion Phase, enrollment into five indication-specific cohort expansions was initiated once the minimum efficacious dose level was reached. Subjects with colorectal, head and neck, non-small cell lung, ovarian, and prostate cancer will be selected based on prospective, tumor tissue genetic profiling using Next Generation Screening (NGS) and must have tumors that harbor a minimum of two genomic alterations hypothesized to confer sensitivity to Chk1 inhibition. The Dose Escalation Phase will continue concurrently until the MTD and Recommended Phase 2 Dose are identified. About the SRA737 Chemotherapy Combination Trial Design  This first-in-human Phase 1, multicenter study consists of two stages: In Stage 1, a triplet combination (SRA737 with gemcitabine and cisplatin) is being evaluated in subjects with solid tumors. Cohorts consisting of three to six subjects will receive escalating doses of SRA737. Intensive PK and pharmacodynamic assessments will be obtained on all subjects. Enrolment for this stage has concluded and the study has transitioned to Stage 2. In the Dose Escalation Phase of Stage 2, cohorts of three to six subjects will be given escalating doses of SRA737 on an intermittent schedule in addition to low-dose gemcitabine until the combination MTD is reached. The starting dose of SRA737 for the first cohort was 40 mg. SRA737 will be administered orally on days 2, 3, 9, 10, 16 & 17 of a 28-day cycle; 300 mg/m2 of gemcitabine will be administered intravenously on days 1, 8, & 15. Once the MTD of SRA737 in combination with gemcitabine has been identified, the Cohort Expansion Phase of Stage 2 will begin. Qualifying patients will be enrolled into two indication-specific cohort expansions, bladder cancer and pancreatic cancer. To qualify for enrolment into these cohorts, the subject's tumor must have a confirmed minimum of two genomic alterations hypothesized to confer sensitivity to Chk1 inhibition, determined using NGS. About the SRA737 ASCO 2017 Poster Presentations Two "Trials in Progress" posters describing the innovative Phase 1 clinical designs for SRA737 are being presented today at the 2017 ASCO Annual Meeting. The posters are available on the company's website at www.sierraoncology.com Title: A phase I study of SRA737 (formerly known as CCT245737) administered orally in patients with advanced cancer. Trials in Progress Abstract: #TPS2607 Poster: #93b Poster Session: Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics Date and Time: Monday, June 5, 2017, 8:00 – 11:30am CT Location: McCormick Place, Event room: Hall A, 2301 S King Dr., Chicago, Illinois Title: A phase I study of oral SRA737 (formerly CCT245737) given in combination with gemcitabine plus cisplatin or gemcitabine alone in patients with advanced cancer. Trials in Progress Abstract: #TPS2613 Poster: #96b Poster Session: Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics Date and Time: Monday, June 5, 2017, 8:00 – 11:30am CT Location: McCormick Place, Event room: Hall A, 2301 S King Dr., Chicago, Illinois About Sierra Oncology Sierra Oncology is a clinical stage drug development company advancing next generation DNA Damage Response (DDR) therapeutics for the treatment of patients with cancer. Our lead drug candidate, SRA737, is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of important cell cycle checkpoints and central mediator of the DDR network. SRA737 is currently being investigated in two Phase 1 clinical trials in patients with advanced cancer. Sierra Oncology is also advancing SRA141, a potent, selective, orally bioavailable small molecule inhibitor of Cell division cycle 7 kinase (Cdc7) undergoing preclinical development. Cdc7 is a key regulator of DNA replication and is involved in the DDR network, making it a compelling emerging target for the potential treatment of a broad range of tumor types. For more information, please visit www.sierraoncology.com. Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding Sierra Oncology's anticipated clinical development, trial designs, target indications, timing of updated data, expectations from current data and potential benefits of Sierra Oncology's product candidates. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. These statements are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described in the forward-looking statements. Such forward-looking statements are subject to risks and uncertainties, including, among others, the risk that Sierra Oncology may be unable to successfully develop and commercialize product candidates, SRA737 and SRA141 are at early stages of development and may not demonstrate safety and efficacy or otherwise produce positive results, Sierra Oncology may experience delays in the preclinical and anticipated clinical development of SRA737 or SRA141, Sierra Oncology may be unable to acquire additional assets to build a pipeline of additional product candidates, Sierra Oncology's third-party manufacturers may cause its supply of materials to become limited or interrupted or fail to be of satisfactory quantity or quality, Sierra Oncology's cash resources may be insufficient to fund its current operating plans and it may be unable to raise additional capital when needed, Sierra Oncology may be unable to obtain and enforce intellectual property protection for its technologies and product candidates and the other factors described under the heading "Risk Factors" set forth in Sierra Oncology's filings with the Securities and Exchange Commission from time to time. Sierra Oncology undertakes no obligation to update the forward-looking statements contained herein or to reflect events or circumstances occurring after the date hereof, other than as may be required by applicable law.


News Article | June 11, 2017
Site: www.eurekalert.org

The drug overdose epidemic is largely driven by opioids, which continue to be prescribed for chronic pain despite recommendations to use non-opioids for most cases. A new review published in the British Journal of Pharmacology examines the interaction between pain and the abuse of opioids, and investigates the circuits in the brain that may be behind this link. The review is part of a special theme issue on Emergent Areas of Opioid Pharmacology. "We have shown that the brain's natural opioid system is drastically changed by the presence of pain, and these changes may very well contribute to the difficulty of treating chronic pain with opioids," said first author Adrianne Wilson-Poe, PhD of the Washington University in Saint Louis School of Medicine. "We have just glimpsed the tip of the iceberg when it comes to pain's effect on the brain, however, and we need a lot more research and grant funding to get to the bottom of the extremely complex interaction between drug abuse and pain." She and senior author Jose Moron-Concepcion, PhD, Associate Professor in the Department of Anesthesiology at Washington University, note that without a fundamental understanding of pain-induced changes in the brain and how these adaptations interact with subsequent drug exposure, investigators are merely fishing for solutions to the opioid crisis. "Our work is attacking this problem head-on by diligently characterizing the mechanisms involved in pain, addiction, and the interaction between them," said Dr. Wilson-Poe. "We envision a future where chronic pain is considered a disease in its own right, not merely a symptom of some other biological process." The review stresses that opioids are the most powerful analgesics known to man, and their continued use in the treatment of severe pain is inevitable; however, opioid therapy of the future must look very different from how it does today. Efforts to address this issue include a 2016 guideline by the Centers for Disease Control and Prevention that recommends using non-opioids for most cases of chronic pain, using the lowest effective dose when prescribing opioids, and ensuring that patients who are treated with opioids are closely monitored. The review is part of a larger themed issue, 'Emergent Areas of Opioid Pharmacology,' that will publish at a later time. The National Institute on Drug Abuse notes that the emergence of illicitly manufactured synthetic opioids including fentanyl, carfentanil, and their analogues represents an escalation of the ongoing opioid overdose epidemic. Also, prescription opioid misuse is a significant risk factor for heroin use, and 80% of heroin users first misuse prescription opioids. Full citation: "The dynamic interaction between pain and opioid misuse." Adrianne R. Wilson-Poe, & Jose A. Morón. British Journal of Pharmacology; Published Online: June 12, 2017 (DOI: 10.1111/bph.13873). The British Journal of Pharmacology is a broad-based journal giving leading international coverage of all aspects of pharmacology research. Its scope includes all aspects of pharmacology from hypothesis generation and target validation through to model development, safety pharmacology and to early translational research. BJP's 2015 Impact Factor is 5.259, and as such it is a leading general research pharmacology journal (Thomson Reuters Science Citation Index). The British Pharmacological Society is a charity with a mission to promote and advance the whole spectrum of pharmacology. Founded in 1931, it is now a global community at the heart of pharmacology, with over 3,500 members from more than 60 countries worldwide. The Society leads the way in the research and application of pharmacology around the world through its scientific meetings, educational resources and peer-reviewed journals: the British Journal of Clinical Pharmacology, Pharmacology Research & Perspectives, and the British Journal of Pharmacology, which includes the Concise Guide to PHARMACOLOGY, featuring open access overviews of the key properties of over 1,700 human therapeutic targets and their drugs, and links to http://www. . Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical, and scholarly journals, combined with our digital learning, assessment and certification solutions help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their


The study is a double-blind, placebo-controlled, single-dose, dose-escalation phase I clinical study to investigate the pharmacokinetics and safety/tolerability of KL1333 in healthy subjects. The study is planned to encompass a total of 60 healthy volunteers and will be fully performed by Yungjin Pharm. KL1333 is in development for the treatment of genetic mitochondrial diseases, such as MELAS and Kearns-Sayre syndrome, for which there are no current medicines. "This is a valuable milestone in our goal to offer patients with genetic mitochondrial disease a new treatment option. Furthermore, it is an important starting point in our collaboration with Yungjin Pharm", said Erik Kinnman, CEO of NeuroVive. "We visited the clinical site just a couple a weeks ago and were very impressed by their extensive experience and professionalism in handling early clinical phase studies", said Magnus Hansson, Chief Medical Officer of NeuroVive. The principal investigator for the study is Professor Kyung-Sang Yu MD, PhD at the Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine. "We are excited about the collaboration with NeuroVive, and the initiation of this clinical program is a significant step forward in the development of innovative medicines in this area with great medical needs", Su Jun Park, CEO of Yungjin Pharm. On 2 May 2017, Yungjin Pharm granted NeuroVive exclusive global rights to develop and commercialize KL1333, except in Korea and Japan, where Yungjin Pharm retains full rights. Both companies will continue to develop KL1333 in their respective markets, primarily for the treatment of genetic mitochondrial disorders. NeuroVive plans to initiate a complementary European and/or US based phase I study in early 2018. For further information about the study, please visit: https://clinicaltrials.gov/ct2/show/NCT03056209 For investor relations and media questions, please contact: KL1333 is a potent modulator of the cellular levels of NAD+, a central coenzyme in the cell's energy metabolism. KL1333 has in preclinical studies been demonstrated to increase mitochondrial energy output, reduce lactate accumulation, diminish the formation of free radicals, and to have long-term beneficial effects on energy metabolism. It is in clinical development stage for chronic oral treatment of primary genetic mitochondrial disorders such as MELAS, KSS, CPEO, PEO, Pearson, MERRF and Alpers syndrome. Its mode of action is complementary to that of NVP015, which is intended to alleviate acute episodes of energy crises in genetic mitochondrial disorders with dysfunction in respiratory complex I and to NVP025, intended to protect the mitochondria in skeletal muscle from dysfunctional calcium handling and consequential muscle wasting. Approximately 12 in every 100,000 people suffer from a genetic mitochondrial disorder. Mitochondrial disorders usually present in early childhood. KL1333 qualifies for orphan drug designation in the US and Europe during clinical development, enabling a faster and less costly route to market, and a higher price. In 2016, the orphan drug market amounted to USD 114 billion and in the same year, the average annual cost for the treatment of a single patient was an estimated USD 140,443 (approx. 1.3 million SEK).1 Yungjin Pharm Co. Ltd., established in 1952, has been playing a major role as a forerunner in the Korean pharmaceutical industry for half a century. With the inspiring mission statement, "To relieve the suffering of mankind from diseases with our innovative, effective and safe pharmaceutical products", they have shown a successful contribution not only within Korea, but also through global expansion. As a result, they have received a total of 25 awards including the President Award for Superior Product Development, the Prime Minister Award, Industry Award and many more. These accomplishments demonstrate their sustainability and commitment to the development of innovative products and business excellence in both overseas and domestic segments. The company is listed on the South Korean stock market, KOSPI (KRX 003520). NeuroVive Pharmaceutical AB is a leader in mitochondrial medicine, with one project in clinical phase II development for the prevention of moderate to severe traumatic brain injury (NeuroSTAT®) and one project in clinical phase I (KL1333). The R&D portfolio consists of several late stage research programs in areas ranging from genetic mitochondrial disorders to cancer and metabolic diseases such as NASH. The company's strategy is to advance drugs for rare diseases through clinical development and into the market. The strategy for projects within larger indications outside the core focus area is out-licensing in the preclinical phase. NeuroVive is listed on Nasdaq Stockholm, Sweden (ticker: NVP). The share is also traded on the OTCQX Best Market in the US (OTC: NEVPF). This information is information that NeuroVive Pharmaceutical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 10:30 a.m. CEST on 27 June 2017. This information was brought to you by Cision http://news.cision.com http://news.cision.com/neurovive-pharmaceutical/r/neurovive-and-yungjin-pharm-start-clinical-development-in-genetic-mitochondrial-disease,c2295980 The following files are available for download: To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/neurovive-and-yungjin-pharm-start-clinical-development-in-genetic-mitochondrial-disease-300480177.html


NeuroVive Pharmaceutical AB (Nasdaq Stockholm: NVP, OTCQX: NEVPF) and Yungjin Pharm Corporation Ltd (South Korea Stock Market, KRX 003520) today announced that the clinical phase I study of KL1333 has started in Korea and that the first healthy volunteer has been enrolled. The study is a double-blind, placebo-controlled, single-dose, dose-escalation phase I clinical study to investigate the pharmacokinetics and safety/tolerability of KL1333 in healthy subjects. The study is planned to encompass a total of 60 healthy volunteers and will be fully performed by Yungjin Pharm. KL1333 is in development for the treatment of genetic mitochondrial diseases, such as MELAS and Kearns-Sayre syndrome, for which there are no current medicines. "This is a valuable milestone in our goal to offer patients with genetic mitochondrial disease a new treatment option. Furthermore, it is an important starting point in our collaboration with Yungjin Pharm", said Erik Kinnman, CEO of NeuroVive. "We visited the clinical site just a couple a weeks ago and were very impressed by their extensive experience and professionalism in handling early clinical phase studies", said Magnus Hansson, Chief Medical Officer of NeuroVive. The principal investigator for the study is Professor Kyung-Sang Yu MD, PhD at the Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine. "We are excited about the collaboration with NeuroVive, and the initiation of this clinical program is a significant step forward in the development of innovative medicines in this area with great medical needs", Su Jun Park, CEO of Yungjin Pharm. On 2 May 2017, Yungjin Pharm granted NeuroVive exclusive global rights to develop and commercialize KL1333, except in Korea and Japan, where Yungjin Pharm retains full rights. Both companies will continue to develop KL1333 in their respective markets, primarily for the treatment of genetic mitochondrial disorders. NeuroVive plans to initiate a complementary European and/or US based phase I study in early 2018. For further information about the study, please visit: https://clinicaltrials.gov/ct2/show/NCT03056209 For investor relations and media questions, please contact: KL1333 is a potent modulator of the cellular levels of NAD+, a central coenzyme in the cell's energy metabolism. KL1333 has in preclinical studies been demonstrated to increase mitochondrial energy output, reduce lactate accumulation, diminish the formation of free radicals, and to have long-term beneficial effects on energy metabolism. It is in clinical development stage for chronic oral treatment of primary genetic mitochondrial disorders such as MELAS, KSS, CPEO, PEO, Pearson, MERRF and Alpers syndrome. Its mode of action is complementary to that of NVP015, which is intended to alleviate acute episodes of energy crises in genetic mitochondrial disorders with dysfunction in respiratory complex I and to NVP025, intended to protect the mitochondria in skeletal muscle from dysfunctional calcium handling and consequential muscle wasting. Approximately 12 in every 100,000 people suffer from a genetic mitochondrial disorder. Mitochondrial disorders usually present in early childhood. KL1333 qualifies for orphan drug designation in the US and Europe during clinical development, enabling a faster and less costly route to market, and a higher price. In 2016, the orphan drug market amounted to USD 114 billion and in the same year, the average annual cost for the treatment of a single patient was an estimated USD 140,443 (approx. 1.3 million SEK).1 Yungjin Pharm Co. Ltd., established in 1952, has been playing a major role as a forerunner in the Korean pharmaceutical industry for half a century. With the inspiring mission statement, "To relieve the suffering of mankind from diseases with our innovative, effective and safe pharmaceutical products", they have shown a successful contribution not only within Korea, but also through global expansion. As a result, they have received a total of 25 awards including the President Award for Superior Product Development, the Prime Minister Award, Industry Award and many more. These accomplishments demonstrate their sustainability and commitment to the development of innovative products and business excellence in both overseas and domestic segments. The company is listed on the South Korean stock market, KOSPI (KRX 003520). NeuroVive Pharmaceutical AB is a leader in mitochondrial medicine, with one project in clinical phase II development for the prevention of moderate to severe traumatic brain injury (NeuroSTAT®) and one project in clinical phase I (KL1333). The R&D portfolio consists of several late stage research programs in areas ranging from genetic mitochondrial disorders to cancer and metabolic diseases such as NASH. The company's strategy is to advance drugs for rare diseases through clinical development and into the market. The strategy for projects within larger indications outside the core focus area is out-licensing in the preclinical phase. NeuroVive is listed on Nasdaq Stockholm, Sweden (ticker: NVP). The share is also traded on the OTCQX Best Market in the US (OTC: NEVPF). This information is information that NeuroVive Pharmaceutical AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 10:30 a.m. CEST on 27 June 2017. This information was brought to you by Cision http://news.cision.com http://news.cision.com/neurovive-pharmaceutical/r/neurovive-and-yungjin-pharm-start-clinical-development-in-genetic-mitochondrial-disease,c2295980 The following files are available for download:


News Article | February 22, 2017
Site: www.prweb.com

NDA Partners Chairman Carl Peck, MD, announced today that Dr. Daniel Spyker, PhD, MD former Acting Deputy Director in the FDA CDRH Division of Cardiovascular, Respiratory, and Neurological Devices and Medical Officer in CDER’s Pilot Drug Evaluation Staff has joined the company as an Expert Consultant. In Dr. Spyker’s accomplished career, he held positions as Senior Director of Drug Safety and Pharmacovigilance at Alexza Pharmaceuticals; Director, Pharmacokinetics and Pharmacodynamic Sciences, Genentech, where he established the clinical pharmacology unit; and Senior Medical Director, Clinical Risk Assessment and Coordination Department at Purdue Pharma. Dr. Spyker was a member of the Internal Medicine faculty in the Division of Clinical Pharmacology at the University of Virginia for 10 years, where he fostered and nurtured the Blue Ridge Poison Center. He was also founder and CEO of a software company specializing in poison center data collection and Bayesian pharmacokinetic applications. “Dr. Daniel Spkyer’s knowledge and expertise of cardiovascular, respiratory, and neurological devices at FDA and in the Industry, in addition to his expertise in quantitative clinical pharmacology and toxicology, make him an excellent addition to NDA Partners. He will bring great value to our medical device clients and we are very pleased to welcome him,” said Dr. Feigal, who heads NDA Partners’ Medical Device Practice. Dr. Spyker earned his PhD from the University of Minnesota in Electrical Engineering and Mathematics, his MD from the University of Virginia, and MS from Purdue University. He is board certified in Internal Medicine, a diplomate of the American Board of Medical Toxicology, and diplomate of the American Board of Clinical Pharmacology. About NDA Partners NDA Partners is a strategy consulting firm specializing in expert product development and regulatory advice to the medical products industry and associated service industries such as law firms, investment funds and government research agencies. The highly experienced Principals and Premier Experts of NDA Partners include three former FDA Center Directors; the former Chairman of the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK; an international team of more than 100 former pharmaceutical industry and regulatory agency senior executives; and an extensive roster of highly proficient experts in specialized areas including nonclinical development, toxicology, pharmacokinetics, CMC, medical device design control and quality systems, clinical development, regulatory submissions, and development program management. Services include product development and regulatory strategy, expert consulting, high-impact project teams, and virtual product development teams.


News Article | February 23, 2017
Site: www.eurekalert.org

A new analysis indicates that not obtaining a medication the first time it is prescribed--called initial medication non-adherence--is common among patients within the Catalan health system in Spain. In the analysis of some 1.6 million patients with 2.9 million prescriptions, the prevalence of total initial medication non-adherence was 17.6% of prescriptions. Predictors were younger age, American nationality, having a pain-related or mental disorder, and being treated by a substitute/resident general practitioner in a teaching center. "We are especially concerned about the high rates of initial medication non-adherence in chronic treatments such as insulins, statins, or antidepressants and suspect that it is also related to an increase in costs, so we are designing an intervention targeting high risk patients," said Dr. Maria Rubio-Valera, senior author of the British Journal of Clinical Pharmacology study.

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