Cts-Clinical and Translational Science最新文献

{"title":"Pharmacokinetics, pharmacodynamics, and safety of asundexian in healthy Chinese and Japanese volunteers, and comparison with Caucasian data","authors":"Huijun Chen,&nbsp;Kensei Hashizume,&nbsp;Friederike Kanefendt,&nbsp;Christine Brase,&nbsp;Sebastian Schmitz,&nbsp;Tianxing Liu","doi":"10.1111/cts.13895","DOIUrl":"10.1111/cts.13895","url":null,"abstract":"<p>There is an unmet clinical need for effective anticoagulant therapies for the management of thromboembolic diseases that are not associated with a relevant risk of bleeding. Asundexian (BAY 2433334) is an oral, direct, small-molecule inhibitor of activated factor XI (FXIa). Phase I data from healthy Caucasian male participants indicated predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles and no clinically relevant bleeding-related adverse events (AEs). Reported here are data from two phase I, randomized, placebo-controlled, single- and multiple-dose escalation studies of asundexian conducted in 60 healthy men: 24 Japanese and 36 Chinese. Baseline characteristics were comparable between the treatment groups. All treatment-emergent AEs were mild, with no serious AEs or AEs of special interest reported. Systemic exposure to asundexian increased dose proportionally after single or multiple dosing, with relatively low accumulation following multiple once-daily dosing in both Chinese and Japanese volunteers. Asundexian induced dose-dependent prolongation of activated partial thromboplastin time and inhibition of FXIa activity, with no effects on prothrombin time or FXI concentration in Japanese participants. There were no clinically relevant interethnic differences in PK profile across the Japanese, Chinese, and Caucasian (data from the previous phase I study) participants and no clinically relevant difference in PD response between Japanese and Caucasian participants.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetics and pharmacodynamics of itepekimab in adults with moderate-to-severe atopic dermatitis: Results from two terminated phase II trials","authors":"Matthew P. Kosloski,&nbsp;Emma Guttman-Yassky,&nbsp;Michael J. Cork,&nbsp;Margitta Worm,&nbsp;Dong-Ho Nahm,&nbsp;Xiaoping Zhu,&nbsp;Marcella K. Ruddy,&nbsp;Sivan Harel,&nbsp;Mohamed A. Kamal,&nbsp;Hélène Goulaouic,&nbsp;Christine R. Xu,&nbsp;Elena Avetisova,&nbsp;John D. Davis,&nbsp;Michael C. Nivens,&nbsp;Arsalan Shabbir,&nbsp;Allen Radin","doi":"10.1111/cts.13874","DOIUrl":"10.1111/cts.13874","url":null,"abstract":"<p>Interleukin-33 (IL-33) is a proinflammatory alarmin cytokine released by damaged epithelial tissue cells that initiates and amplifies both type 1 and type 2 inflammatory cascades. A role for IL-33 in atopic dermatitis (AD; a chronic, relapsing type 2 inflammatory disease of the skin) has been proposed. Itepekimab is a novel human IgG4P monoclonal antibody against IL-33, currently in clinical development for chronic obstructive pulmonary disease (COPD). Two global phase II studies—a dose-ranging itepekimab monotherapy study (NCT03738423) and a proof-of-concept study of itepekimab alone and in combination with dupilumab (NCT03736967)—were conducted in patients with moderate-to-severe AD to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy; both studies were terminated following an interim analysis of the proof-of-concept study, which failed to demonstrate the efficacy of itepekimab. In these two studies, itepekimab exhibited linear and dose-proportional pharmacokinetics. Pharmacodynamics of total IL-33 indicated that itepekimab saturated binding to the target in serum at 300 mg q2w and q4w doses, and decreased blood eosinophil counts. Concentration–time profiles of itepekimab and total IL-33 were similar for itepekimab with or without dupilumab, and between East Asian and non-East Asian subgroups. Itepekimab was generally well tolerated, both alone and in combination with dupilumab. The lack of clinical efficacy for itepekimab observed in these studies suggests that IL-33 may not be a key pathogenic driver in moderate-to-severe AD.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dupilumab: Mechanism of action, clinical, and translational science","authors":"Marc R. McCann,&nbsp;Matthew P. Kosloski,&nbsp;Christine Xu,&nbsp;John D. Davis,&nbsp;Mohamed A. Kamal","doi":"10.1111/cts.13899","DOIUrl":"10.1111/cts.13899","url":null,"abstract":"<p>Allergic disease prevalence has increased globally with the subset of type 2 inflammatory diseases playing a substantial role. Type 2 inflammatory diseases may differ in clinical presentation, but they exhibit shared pathophysiology that is targeted by the unique pharmacology of dupilumab. Dupilumab binds to the interleukin (IL)-4 receptor alpha subunit (IL-4Rα) that blocks IL-4 and IL-13 signaling, two key drivers of type 2 inflammation. Herein, we review the mechanism of action and pharmacology of dupilumab, and the clinical evidence that led to the regulatory approvals of dupilumab for the treatment of numerous type 2 inflammatory diseases: atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, eosinophilic esophagitis, and prurigo nodularis.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11288895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenomics polygenic risk score: Ready or not for prime time?","authors":"Sonal Singh,&nbsp;Gabriele Stocco,&nbsp;Katherine N. Theken,&nbsp;Alyson Dickson,&nbsp;QiPing Feng,&nbsp;Jason H. Karnes,&nbsp;Jonathan D. Mosley,&nbsp;Nihal El Rouby","doi":"10.1111/cts.13893","DOIUrl":"10.1111/cts.13893","url":null,"abstract":"<p>Pharmacogenomic Polygenic Risk Scores (PRS) have emerged as a tool to address the polygenic nature of pharmacogenetic phenotypes, increasing the potential to predict drug response. Most pharmacogenomic PRS have been extrapolated from disease-associated variants identified by genome wide association studies (GWAS), although some have begun to utilize genetic variants from pharmacogenomic GWAS. As pharmacogenomic PRS hold the promise of enabling precision medicine, including stratified treatment approaches, it is important to assess the opportunities and challenges presented by the current data. This assessment will help determine how pharmacogenomic PRS can be advanced and transitioned into clinical use. In this review, we present a summary of recent evidence, evaluate the current status, and identify several challenges that have impeded the progress of pharmacogenomic PRS. These challenges include the reliance on extrapolations from disease genetics and limitations inherent to pharmacogenomics research such as low sample sizes, phenotyping inconsistencies, among others. We finally propose recommendations to overcome the challenges and facilitate the clinical implementation. These recommendations include standardizing methodologies for phenotyping, enhancing collaborative efforts, developing new statistical methods to capitalize on drug-specific genetic associations for PRS construction. Additional recommendations include enhancing the infrastructure that can integrate genomic data with clinical predictors, along with implementing user-friendly clinical decision tools, and patient education. Ethical and regulatory considerations should address issues related to patient privacy, informed consent and safe use of PRS. Despite these challenges, ongoing research and large-scale collaboration is likely to advance the field and realize the potential of pharmacogenomic PRS.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug–drug interactions between pemafibrate and statins on pharmacokinetics in healthy male volunteers: Open-label, randomized, 6-sequence, 3-period crossover studies","authors":"Tomohiro Kamimura,&nbsp;Neil Hounslow,&nbsp;Hideki Suganami,&nbsp;Ryohei Tanigawa","doi":"10.1111/cts.13900","DOIUrl":"10.1111/cts.13900","url":null,"abstract":"<p>Elevated triglyceride levels are associated with an increased risk of cardiovascular events despite guideline-based statin treatment of low-density lipoprotein cholesterol. Peroxisome proliferator-activated receptor α (PPARα) agonists exert a significant triglyceride-lowering effect. However, combination therapy of PPARα agonists with statins poses an increased risk of rhabdomyolysis, which is rare but a major concern of the combination therapy. Pharmacokinetic interaction is suspected to be a contributing factor to the risk. To examine the potential for combination therapy with the selective PPARα modulator (SPPARMα) pemafibrate and statins, drug–drug interaction studies were conducted with open-label, randomized, 6-sequence, 3-period crossover designs for the combination of pemafibrate 0.2 mg twice daily and each of 6 statins once daily: pitavastatin 4 mg/day (<i>n</i> = 18), atorvastatin 20 mg/day (<i>n</i> = 18), rosuvastatin 20 mg/day (<i>n</i> = 29), pravastatin 20 mg/day (<i>n</i> = 18), simvastatin 20 mg/day (<i>n</i> = 20), and fluvastatin 60 mg/day (<i>n</i> = 19), involving healthy male volunteers. The pharmacokinetic parameters of pemafibrate and each of the statins were similar regardless of coadministration. There was neither an effect on the systemic exposure of pemafibrate nor a clinically important increase in the systemic exposure of any of the statins on the coadministration although the systemic exposure of simvastatin was reduced by about 15% and its open acid form by about 60%. The HMG-CoA reductase inhibitory activity in plasma samples from the simvastatin and pemafibrate combination group was about 70% of that in the simvastatin alone group. In conclusion, pemafibrate did not increase the systemic exposure of statins, and vice versa, in healthy male volunteers.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11287820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and accuracy of mobile QT interval monitoring strategies in bedaquiline-enhanced prophylactic leprosy treatment","authors":"Auke T. Bergeman,&nbsp;Said Nourdine,&nbsp;Alberto Piubello,&nbsp;Zahara Salim,&nbsp;Sofie M. Braet,&nbsp;Abdallah Baco,&nbsp;Silahi H. Grillone,&nbsp;Rian Snijders,&nbsp;Carolien Hoof,&nbsp;Achilleas Tsoumanis,&nbsp;Harry van Loen,&nbsp;Younoussa Assoumani,&nbsp;Aboubacar Mzembaba,&nbsp;Nimer Ortuño-Gutiérrez,&nbsp;Epco Hasker,&nbsp;Christian van der Werf,&nbsp;Bouke C. de Jong","doi":"10.1111/cts.13861","DOIUrl":"10.1111/cts.13861","url":null,"abstract":"<p>Some anti-mycobacterial drugs are known to cause QT interval prolongation, potentially leading to life-threatening ventricular arrhythmia. However, the highest leprosy and tuberculosis burden occurs in settings where electrocardiographic monitoring is challenging. The feasibility and accuracy of alternative strategies, such as the use of automated measurements or a mobile electrocardiogram (mECG) device, have not been evaluated in this context. As part of the phase II randomized controlled BE-PEOPLE trial evaluating the safety of bedaquiline-enhanced post-exposure prophylaxis (bedaquiline and rifampicin, BE-PEP, versus rifampicin, SDR-PEP) for leprosy, all participants had corrected QT intervals (QTc) measured at baseline and on the day after receiving post-exposure prophylaxis. The accuracy of mECG measurements as well as automated 12L-ECG measurements was evaluated. In total, 635 mECGs from 323 participants were recorded, of which 616 (97%) were of sufficient quality for QTc measurement. Mean manually read QTc on 12L-ECG and mECG were 394 ± 19 and 385 ± 18 ms, respectively (<i>p</i> &lt; 0.001), with a strong correlation (<i>r</i> = 0.793). The mean absolute QTc difference between both modalities was 11 ± 10 ms. Mean manual and automated 12L-ECG QTc were 394 ± 19 and 409 ± 19 ms, respectively (<i>n</i> = 636; <i>p</i> &lt; 0.001), corresponding to moderate agreement (<i>r</i> = 0.655). The use of a mECG device for QT interval monitoring was feasible and yielded a median absolute QTc error of 8 ms. Automated QTc measurements were less accurate, yielding longer QTc intervals.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11286973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the net financial benefits of employing digital endpoints in clinical trials","authors":"Joseph A. DiMasi,&nbsp;Abigail Dirks,&nbsp;Zachary Smith,&nbsp;Sarah Valentine,&nbsp;Jennifer C. Goldsack,&nbsp;Thomas Metcalfe,&nbsp;Upinder Grewal,&nbsp;Lada Leyens,&nbsp;Ute Conradi,&nbsp;Daniel Karlin,&nbsp;Lesley Maloney,&nbsp;Kenneth A. Getz,&nbsp;Bert Hartog","doi":"10.1111/cts.13902","DOIUrl":"10.1111/cts.13902","url":null,"abstract":"<p>In the last few decades, developers of new drugs, biologics, and devices have increasingly leveraged digital health technologies (DHTs) to assess clinical trial digital endpoints. To our knowledge, a comprehensive assessment of the financial net benefits of digital endpoints in clinical trials has not been conducted. We obtained data from the Digital Medicine Society (DiMe) Library of Digital Endpoints and the US clinical trials registry, ClinicalTrials.gov. The benefit metrics are changes in trial phase duration and enrollment associated with the use of digital endpoints. The cost metric was obtained from an industry survey of the costs of including digital endpoints in clinical trials. We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess financial value. The value measure is the increment in eNPV that occurs when digital endpoints are employed. We also calculated a return on investment (ROI) as the ratio of the estimated increment in eNPV to the mean digital endpoint implementation cost. For phase II trials, the increase in eNPV varied from $2.2 million to $3.3 million, with ROIs between 32% and 48% per indication. The net benefits were substantially higher for phase III trials, with the increase in eNPV varying from $27 million to $40 million, with ROIs that were four to six times the investment. The use of digital endpoints in clinical trials can provide substantial extra value to sponsors developing new drugs, with high ROIs.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational pharmacokinetic/pharmacodynamic model for mRNA-0184, an investigational therapeutic for the treatment of heart failure","authors":"Neeraj Kaushal,&nbsp;Husain Attarwala,&nbsp;Mir Javid Iqbal,&nbsp;Rajnish Saini,&nbsp;Linh Van,&nbsp;Min Liang","doi":"10.1111/cts.13894","DOIUrl":"10.1111/cts.13894","url":null,"abstract":"<p>Heart failure (HF) is a complex, progressive disorder that is associated with substantial morbidity and mortality on a global scale. Relaxin-2 is a naturally occurring hormone that may have potential therapeutic benefit for patients with HF. To investigate the therapeutic potential of relaxin in the treatment of patients with HF, mRNA-0184, a novel, investigational, lipid nanoparticle (LNP)–encapsulated mRNA therapy that encodes for human relaxin-2 fused to variable light chain kappa (Rel2-vlk) was developed. A translational semi-mechanistic population pharmacokinetic (PK)/pharmacodynamic (PD) model was developed using data from non-human primates at dose levels ranging from 0.15 to 1 mg/kg. The PK/PD model was able to describe the PK of Rel2-vlk mRNA and translated Rel2-vlk protein in non-human primates adequately with relatively precise estimates. The preclinical PK/PD model was then scaled allometrically to determine the human mRNA-0184 dose that would achieve therapeutic levels of Rel2-vlk protein expression in patients with stable HF with reduced ejection fraction. Model-based simulations derived from the scaled PK/PD model support the selection of 0.025 mg/kg as an appropriate starting human dose of mRNA-0184 to achieve average trough relaxin levels between 1 and 2.5 ng/mL, which is the potential exposure for cardioprotective action of relaxin.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.13894","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141770544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implementation of a pharmacogenetic panel-based test for pharmacotherapy-based supportive care in an adult oncology clinic","authors":"Emily J. Cicali,&nbsp;Elizabeth Eddy,&nbsp;Yan Gong,&nbsp;Amanda L. Elchynski,&nbsp;Kim Pena del Aguila,&nbsp;Tala Basha,&nbsp;Karen C. Daily,&nbsp;Lauren Dickson,&nbsp;Steven Fischer,&nbsp;Erin Hastings-Monari,&nbsp;Dennie Jones Jr.,&nbsp;Brian H. Ramnaraign,&nbsp;David L. DeRemer,&nbsp;Thomas J. George,&nbsp;Rhonda M. Cooper-DeHoff","doi":"10.1111/cts.13890","DOIUrl":"10.1111/cts.13890","url":null,"abstract":"<p>The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel-based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non-hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient-reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (<i>n</i> = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel-based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parkinson's disease: Still waiting for a cure","authors":"D. Kevin Kwok","doi":"10.1111/cts.13898","DOIUrl":"10.1111/cts.13898","url":null,"abstract":"&lt;p&gt;I am trained as a clinical pharmacist and have worked in the biopharmaceutical industry for over 30 years which provides me a depth of understanding of the complexities of drug development and the regulatory process. Fifteen years ago, I was diagnosed with Young Onset Parkinson's Disease (YOPD) and have experienced firsthand the Parkinson's journey and its progression over time.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; With this unique vantage, I have a front row seat in observing and commenting on the lengthy duration and challenges in developing novel treatments that offer meaningful benefit to me and my Parkinson's patient tribe.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;In May 2024, I was invited to attend the Michael J. Fox Foundation's Annual Parkinson's Progression Marker Initiative (PPMI) Investigators' Meeting.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; PPMI is a biomarker discovery initiative where I have served as a patient advisor for the past 7 years. Over these years, I have greatly enjoyed attending these meetings and learning the updates from this global neuroscience community.&lt;/p&gt;&lt;p&gt;Each year, this event kicks off where a growing conference room of over 300 investigators, biopharma scientists, regulatory advisors, and a few patients all stand up and introduce themselves. This year, I introduced myself with the tagline, “Kevin Kwok, Patient Council Member…Still waiting for a cure.”&lt;/p&gt;&lt;p&gt;This “Still waiting for a cure” tagline elicited several waves and salutes from fellow attendees who have become ardent supporters and friends over my years as a Parkinson's patient advocate. Included in this group of supporters is Dr. Diane Stephenson from Critical Path for Parkinson's and Dr. Billy Dunn, former Neurology Division Head at the Food and Drug Administration.&lt;/p&gt;&lt;p&gt;During his panel, Dr. Billy Dunn called on me by asking what year it was when I had traveled to the FDA headquarters in Bethesda where, as part of PDUFA,&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt; I had provided patient testimony on my experience living with Parkinson's.&lt;/p&gt;&lt;p&gt;I responded this patient event was September 2015, which led me to reflect on what had changed since that testimony. Here are excerpts from my personal blog 9 years ago after participating at this FDA led patient meeting (see Box 1).&lt;/p&gt;&lt;p&gt;My FDA patient testimony blog on living with Parkinson's disease has since been circulated to many leading neuroscientists, including Dr. Billy Dunn and others. Subsequently I have been invited to participate in numerous drug development workshops including those sponsored by Critical Path, the FDA and industry to provide the patient lived experience.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; I even pivoted my own career to lead patient engagement activities with a previous employer by incorporating patient perspectives in developing their select programs. I have personally witnessed Patient Focused Drug Development (PFDD) evolve from being a token afterthought implemented at late stages of clinical development to participating on panels","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 7","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}