Apotekarsocieteten’s Post

Pharmacogenomics is where the intricacies of genetic code meet the precision of drug development. 🔬 Discover how pharmacogenomics enhances therapeutic precision in pharmaceutical research – and what that means for the future of medicine. 👇 https://lnkd.in/eaqUUkPG #ClinicalTrials #PrecisionMedicine #Pharmacogenomics

FDA JUST RELEASED ‼️ Clinical Pharmacology Considerations for the Development of Oligonucleotide Therapeutics Guidance for Industry 💠FOREWORD💠 Oligonucleotide therapeutics are an emerging therapeutic modality with increasing numbers of drugs in development. Many antisense and small interfering RNA (#siRNA) oligonucleotide therapeutics have been #FDAapproved in recent years. In addition, many #oligonucleotidetherapeutics are currently in development to treat #raredisease and #commondiseases alike. Oligonucleotide therapeutics include a wide variety of synthetically modified RNA or RNA/#DNA hybrids that are specifically designed to bind to a #targetRNA sequence to alter RNA expression and/or downstream protein expression. Even within the therapeutic modality, oligonucleotide therapeutics can differ in several ways. 💠SCOPE💠 ‼️This guidance provides recommendations to assist industry in the development of #oligonucleotidetherapeutics under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) and 21 CFR parts 312 and 314. Specifically, this guidance represents the FDA’s recommendations for certain evaluations during #development of oligonucleotide therapeutics, including: 1️⃣ characterizing the potential for QTc interval prolongation, 2️⃣ performing immunogenicity risk assessment, 3️⃣ characterizing the impact of hepatic and renal impairment, 4️⃣ assessing the potential for drug-drug interactions. ‼️This guidance provides recommendations on when to conduct these assessments and what types of assessments are suitable to address the topics listed above. If you like this post follow me on LinkedIn

A Record Year 2023 for Novel Drug Approvals by the FDA/CDER The estimated cost of developing a single FDA-approved drug is around $2.6 billion. The year 2023 has been a remarkable one for the pharmaceutical industry, as the FDA/CDER has approved 56 novel drugs, a 51% increase compared to 2022. #fda #drugapproval #innovation Here are some of the highlights and trends from the novel drug approvals in 2023: 🏆 Pfizer leads the pack with 6 approvals, followed by Biogen with 4, and AstraZeneca, Chiesi, and UCB with 3 each. #Pfizer #Biogen #AstraZeneca #Chiesi #UCB 🩺 Oncology remains the most popular therapeutic area, with 17 approvals, followed by neurology and autoimmune disorders, with 6 each. #Oncology #Neurology #Autoimmune #DrugApprovals 💊 Small molecules account for more than half of the approvals, with 31, followed by therapeutic monoclonal antibodies, with 12. #SmallMolecules #MonoclonalAntibodies #PharmaTrends 🧬 DNA/RNA based drugs, such as gene therapies and antisense oligonucleotides, are gaining traction, with 4 approvals. #GeneTherapy #RNA #Innovation 🌱 Other novel drugs include a natural extract, a radioactive diagnostic agent, and a fusion protein. #NaturalExtract #DiagnosticAgent #FusionProtein The novel drug approvals in 2023 reflect the diversity and innovation of the pharmaceutical industry, as well as the commitment and collaboration of the FDA/CDER to bring safe and effective treatments to the patients who need them. #pharmainnovation #patientcare #healthcareinnovation If you want to learn more about the novel drug approvals in 2023, you can check out this link: https://lnkd.in/gQ_kU7Tr 📰 #DrugApprovals #pharmanews #medicaladvancements 👉👉You can also check out this insightful analysis by Aaher Mullard in #NatureReviews, which covers the historical data of drug approval, the competition and innovation in the field, and the #DrugDiscovery expectations for 2024. You can find Aasher’s article on the following link: https://lnkd.in/ejHvaxT6

Human-Genetic targets for drug development: 1-Drug targets with human genetic evidence are more likely to enter phase II/III clinical trials and are more likely to be approved and launched quickly. 2-  Potential molecular targets related to certain diseases have been identified by genome-wide association studies (GWAS), whole-exome sequencing (WES), and whole-genome sequencing (WGS). 3-In a review published in  MedComm by Xiaoxia Zhang, Wenjun Yu, Yan Li, Aiping Wang, Haiqiang Cao, Yuanlei Fu, the mechanism of action of the eight beneficial LOF mutation targets is listed. Below is the brief description of LOF targets and current status for their respective drugs . #PCSK9 (regulates LDL-C levels) approved and marketed for the treatment of patients with hyperlipidemia. #ANGPTL3 (regulates LDL-C and TG levels) approved and marketed for the treatment of patients with HoFH. #ASGR1 (regulate cholesterol efflux and fatty acid synthesis) currently in the development stage. #HSD17B13 (involved in hepatic lipid metabolism ) currently in Phase II clinical stage. #KHK (one of the rate-limiting enzymes of fructose metabolism) with two drugs currently in Phase II clinical stage. #CIDEB (maintain systemic lipid homeostasis and energy metabolism, no drugs in clinical trials. #GPR75 (LOF has been linked to the prevention of obesity) a new potential target for the treatment of obesity and is still under preclinical trials. Conclusion: Hence, Integration of genetics into the clinical drug development process will be more conducive to promoting the success and approval rates of drug development, and expanding the range of indications for drugs that have been approved or are in clinical trials. But incorporation of modern technologies in the above process plays a key role to its acceleration and development.

📘 I recently dove into "Pharma and Profits" by John LaMattina, former President Pfizer Global Research & Development, and it's probably the best book I've read on the main debate that generally surrounds the pharmaceutical industry: drug pricing. Two insights 💡 from the book truly stood out: 1️⃣ FOCUS ON PRICE VS. VALUE: We often only see the price tag of new drugs, a $1000-pill here, a $475,000 gene therapy there, as these make for sensational headlines 📰 But as LaMattina outlines, this singular focus on price shows a disinterest to dig deeper to understand the current standard of care and value of a medicine. Fundamentally, we should always ask ourselves: 👉1/ How does a drug compare to existing treatments (including surgical and hospital based) in terms of efficacy and safety? 👉2/ How expensive are these other treatments? 👉3/ Without this drug, how many will die or have other adverse events? 👉4/ Without the drug, what is the ultimate cost to the healthcare system? In the case of the $1000-pill for example, which cures hepatitis C in more than 90% of cases in just 12 weeks (costing $84,000/patient), the answers would be: 👉1/ 90% cure rates vs. 40-80% for older treatments 👉2/ generally over $100,000 per treatment 👉3/ approx. 20% of people with chronic hepatitis C would progress to liver cirrhosis, liver cancer and may eventually experience liver failure 👉4/ with liver transplants alone costing around $300,000, and add to that all the post-transplant care and anti-rejection drugs ($40,000 per year per patient for several years), it becomes clear that the $1000-pill provides great value for money. The same exercise can be performed for the $475,000 gene therapy and other innovative medicines. 2️⃣ MEDICINE PRICES AREN’T WHAT’S DRIVING HEALTHCARE COSTS: High drug prices must be what drives healthcare costs, right? Not quite. In fact, as LaMattina outline for the US, pharmaceutical spending has been stable over past decades at around 13% of healthcare spending, while at the same time costs for hospital procedures have continuously been rising, outpacing the rate of inflation. But that’s the US, surely Europe is different? Nope, pharmaceutical expenditure in Europe has remained stable for the past 20 years at an average of around 15% of healthcare spending (https://lnkd.in/eB9ivDrK). This is despite an increase in the use and reliance on pharmaceuticals and the many breakthrough therapies that have emerged. ➡ There are many more insights like these in LaMattina's book. At only 97 pages, the book is short but as insights packed as it gets, and while focusing on the US, most of the principles and reasoning apply to the European context as well. #pharma #healthcare #medicines #healthcarecosts

Liver Cirrhosis Pipeline Assessment, 2023 Updates: FDA, EMA, and PMDA Approvals, Emerging Drugs, Clinical Trials, Therapeutic Analysis, and Growth Prospects | PharmaIN, Gwo Xi Stem Cell Applied Tech #Business #HealthMedicine #MarketingSales #PharmaceuticalsBiotech

FDA Announces Availability of a Final Guidance Clinical Pharmacology Considerations for Antibody-Drug Conjugates On March 1, 2024, the FDA announced the availability of a final guidance for industry entitled Clinical Pharmacology Considerations for Antibody-Drug Conjugates, replacing the February 2022 draft guidance. This final guidance provides recommendations to assist industry and other parties involved in the development of an antibody-drug conjugate (ADC) consisting of a cytotoxic small molecule drug or payload conjugated by a chemical linker to an antibody or antibody fragment. ADCs combine the selectivity of an antibody for a specific target with the potency of a small-molecule drug. Selection of optimal dosing strategies for ADCs requires careful consideration of the pharmacokinetic and pharmacodynamic characteristics of the antibody and the payload because different constituent parts of the ADC can independently impact safety and/or efficacy. For example, a relatively small increase in the systemic exposure of the payload can cause significant adverse reactions that are dose limiting from a safety perspective. As a result, having a thorough understanding of the pharmacokinetics and pharmacodynamics of the ADC and its constituent parts early in development and their relationships to safety and efficacy outcomes is crucial to optimize the dose of the ADC. In addition, the impact of the intrinsic and extrinsic factors on the pharmacokinetics, safety, and efficacy of the ADC should be evaluated in development programs to inform labeling recommendations for use in specific patient subsets. This final guidance addresses the FDA’s current thinking regarding clinical pharmacology considerations and recommendations for ADC development programs, including bioanalytical methods, dosing strategies, dose- and exposure-response analysis, intrinsic factors, QTc assessments, immunogenicity, and drug-drug interactions. #fda CRC Pharma #crc #cro #guidance #clinicalpharmacology #antibodydrugconjugates

I was impressed and delighted to read the recent Editorial in CPT (July 2024) which emphasized the real need to re-think QT testing strategies for peptide, protein and oligonucleotide therapeutics. The opinion is based on several independent sources of compelling evidence co-published in the same issue. Based on the mounting evidence of low QTc prolongation risk, the CPT Editors suggest that new biological and ONT modalities should be presumed to be “innocent until proven guilty”. Do you agree? Some of the new evidence was provided by safety pharmacology experts from Eli Lilly, UCB, Boehringer-Ingelheim and Amgen. Let's do this!

We are thrilled to announce that Tim Lefever from Nalu Bio ,will be sharing his groundbreaking research on less studied phytochemical at the upcoming CannMed Innovation and Investment Summit. Despite the recent popularity of cannabis phytochemicals in the marketplace, little research has been conducted on basic characterization of many of them beyond Δ9-THC, CBD, CBG and CBN. His firm sought to understand some of the in vitro pharmacology, physicochemical characteristics, DMPK/ADME profiles and in vivo toxicity of the following phytochemicals; Δ8-THCV, Δ9-THCV, CBDV, CBCV, CBGV, CBC and cannflavin a. This initial data set and approach is critical for guiding future studies elucidating potential health benefits and identifying the characteristics that can be approved upon with medicinal chemistry towards viable therapeutics. The test articles were investigated for in vitro pharmacology using radioligand binding assays or functional assays (cAMP, arrestin, calcium flux) at the following targets; CB1, CB2, 5HT1a, mu, ppar𝛾, GRP18, GPR55, GPR119, TRPV1, TRPM8 and TRPA1. Physicochemical and DMPK/ADME assays were carried out in duplicate; thermodynamic solubility, logD, MDCK-MDR1 bi-directional permeability, CYP inhibition (8 isoforms) and microsomal stability in human, rat and mouse cells. Finally, toxicity (acute and subchronic) and mechanosensory effects of each test article was carried out across three doses in C. elegans. Tim is an experienced Director with a demonstrated history of 20+ years of preclinical in vivo research and leading effective teams. He spent 9 years at Research Triangle Institute (RTI) managing the research endeavors and team focused on structure activity relationships, abuse liability, pharmacology and pharmacokinetics of cannabinoids. He successfully designed and executed numerous in vivo studies for Federally funded grants (NIH), Federal contracts (FDA, DEA), and Pharmaceutical/Biotech contracts, many under GLP conditions. He spent 3 years at Canopy Growth Corporation working closely with the Chief Medical Officer to develop and implement a product safety program; evaluating potential products for safety and efficacy through preclinical in vivo studies. Tim has been an active member of the INTERNATIONAL CANNABINOID RESEARCH SOCIETY (ICRS) since 2013 and co-hosted the Carolina Cannabinoid Collaborative meeting in 2017. He has authored or co-authored numerous manuscripts and presented research findings at a variety of scientific conferences over the past 20 years. Join us from May 12th to 15th at the JW Marriott Marco Island Beach Resort for #CannMed24 and hear from Tim and other industry leaders. Don't miss out on this incredible opportunity! Learn more about the other speakers and register for the summit here: https://lnkd.in/eB2mpie CannMed Events Medicinal Genomics Advanced Nutrients US LLC

Join ACCP on Wednesday, November 8th at 1:00 - 2:00 PM ET for an outstanding educational event on "From Exogenous Probes to Endogenous Biomarkers: A Paradigm Shift in the Approach to Assess Transporter Mediated Drug-Drug Interactions" https://lnkd.in/emnvPwPm Why is this webinar important to you? Membrane bound drug transporters, expressed in various tissues throughout the body, control the movement of endogenous and exogenous substances in and out of cells at various sites in the body. Some drugs interact with transporters either as substrates or modulators (inhibitors or inducers), therefore, evaluation of transporter mediated drug-drug interactions (DDI) during drug development and post-approval is important to formulate clinical management strategies and ensure the safe and effective use of concomitantly administered drugs. Vikram Arya Manoli Vourvahis Dr. Peter Stopfer