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Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by providing updates on new and anticipated novel drug approvals., Summary: Selected drug approvals anticipated in the 12-month period covering the fourth quarter of 2024 through the third quarter of 2025 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics, as selected from among 51 novel drugs awaiting US Food and Drug Administration approval. New drugs for severe rare diseases, cancers, autoimmune diseases, acute pain, and reversal of anticoagulation are being developed. Additionally, a new cell therapy for treatment of graft-versus-host disease joined the group of novel targeted therapies for various diseases awaiting approval., Conclusion: Novel therapies for treating rare diseases and cancers continue to strengthen the current drug pipeline., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by sharing new and anticipated novel drug approvals., Summary: Selected drug approvals anticipated in the 12-month period covering the third quarter of 2024 through the second quarter of 2025 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics selected from 54 novel drugs awaiting US Food and Drug Administration approval. New cell therapies for treating cancers continue to enter the drug pipeline, while novel targeted therapies for biliary tract, gastric, pancreatic, and breast cancers, as well as 3 subcutaneous versions of already approved drugs given intravenously, are awaiting approval. Additionally, many novel drugs are being developed for treatment of rare and ultra-rare diseases such as hereditary angioedema, macular telangiectasia, congenital adrenal hyperplasia, and Barth syndrome. Two new subcutaneous drugs for hemophilia, a new oral medication for hereditary angioedema, a novel monoclonal antibody for atopic dermatitis, and the first oral penem antibiotic are also in the pipeline., Conclusion: New drugs with various indications for cancers and rare diseases continue to strengthen the drug pipeline., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by providing periodic updates on new and anticipated novel drug approvals., Summary: Selected drug approvals anticipated in the 12-month period covering the second quarter of 2024 through the first quarter of 2025 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics, as selected from 52 novel drugs awaiting US Food and Drug Administration approval. New cellular and gene therapies for cancers continued to strengthen the pipeline, in addition to new drugs targeting previously untreatable conditions. Several novel drugs are being developed for rare and ultra-rare diseases such as hemophilia, Niemann-Pick disease type C, hereditary angioedema, and aromatic l-amino acid decarboxylase deficiency., Conclusion: The current drug pipeline includes new drugs with various indications for cancers and rare diseases as well as diabetes, acute coronary syndrome, chronic skin disorder, and chronic obstructive pulmonary disease., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Artificial intelligence tools promise transformative impacts in drug development. Regulatory agencies face challenges in integrating AI while ensuring reliability and safety in clinical trial approvals, drug marketing authorizations, and post-market surveillance. Incorporating these technologies into the existing regulatory framework and agency practices poses notable challenges, particularly in evaluating the data and models employed for these purposes. Rapid adaptation of regulations and internal processes is essential for agencies to keep pace with innovation, though achieving this requires collective stakeholder collaboration. This article thus delves into the need for adaptations of regulations throughout the drug development lifecycle, as well as the utilization of AI within internal processes of medicine agencies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Oualikene-Gonin, Jaulent, Thierry, Oliveira-Martins, Belgodère, Maison, Ankri and The Scientific Advisory Board of ANSM.)

Purpose: Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by providing periodic updates on new and anticipated novel drug approvals., Summary: Selected drug approvals anticipated in the 12-month period covering the first quarter of 2024 through the fourth quarter of 2024 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics, as selected from 59 novel drugs awaiting US Food and Drug Administration approval. This year's pipeline includes recently added drugs with various indications including oncology, infectious diseases, genetic disorders, and rare diseases. New cellular and gene therapies are rapidly evolving and being studied for several rare diseases and cancers., Conclusion: More oncology agents, including gene therapies, oral agents, and monoclonal antibodies, are in the pipeline this year. Additional diseases targeted by new novel drugs, including cellular and gene therapies, are hemophilia, nonalcoholic steatohepatitis, Alzheimer's disease, and rare diseases such as galactosemia and epidermolysis bullosa., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: About one-fifth of cannabis users, the most commonly used illicit substance, have cannabis use disorder (CUD). Psychiatric disorders and suicide are more common in these patients, and the disability-adjusted life years were reported to be 0.69 million. Pharmacotherapy for CUD is an unmet public health need, as current evidence-based therapies have limited efficacy., Areas Covered: After explaining the pathophysiology of CUD, the effects of emerging pharmacological interventions in its treatment obtained from randomized controlled trials were reviewed in light of mechanisms of action. Superiority over control of cannabidiol, gabapentin, galantamine, nabilone plus zolpidem, nabiximols, naltrexone, PF-04457845, quetiapine, varenicline, and topiramate were observed through the cannabinoid, glutamatergic, γ-aminobutyric acidergic, serotonergic, noradrenergic, dopaminergic, opioidergic, and cholinergic systems. All medications were reported to be safe and tolerable., Expert Opinion: Adding pharmacotherapy to psychotherapy is the optimal treatment for CUD on a case-by-case basis. Drug development to add to psychotherapy is the main path, but time and cost suggest repurposing and repositioning existing drugs. Considering sample size, follow-up, and effect size, further studies using objective tools are necessary. The future of CUD treatment is promising.

Purpose: Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by providing updates on new and anticipated novel drug approvals., Summary: Selected drug approvals anticipated in the 12-month period covering the fourth quarter of 2023 through the third quarter of 2024 are reviewed. The analysis emphasizes drugs selected from 58 novel drugs awaiting FDA approval that are expected to have significant clinical and financial impact in hospitals and clinics. The pipeline includes recently added drugs with various indications, including oncology, infectious diseases such as complicated urinary tract infection and pneumonia, and rare diseases., Conclusion: Cellular and gene therapies continue to strengthen the pipeline as potential new treatment options for genetic disorders, rare diseases, and cancer. Additional diseases treated by new agents include pulmonary arterial hypertension, chronic obstructive pulmonary disease, diabetes, and obesity., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient., Areas Covered: After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action., Expert Opinion: Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

Purpose: Health-system pharmacists play a crucial role in monitoring the pharmaceutical pipeline to manage formularies, allocate resources, and optimize clinical programs for new therapies. This article aims to support pharmacists by sharing new and anticipated novel drug approvals., Summary: Selected drug approvals anticipated in the 12-month period covering the second quarter of 2023 through the first quarter of 2024 are reviewed. The analysis emphasizes drugs expected to have significant clinical and financial impact in hospitals and clinics, as selected from 58 novel drugs awaiting Food and Drug Administration (FDA) approval at the time of data extraction. The pipeline includes drugs with various indications, such as oncology, inflammatory conditions, and rare diseases. Key developments in oncology are highlighted along with notable advancements in treating myelofibrosis, metastatic colorectal cancer, and low-grade gliomas. Cellular and gene therapies are anticipated to emerge prominently as treatment options for severe hemophilia A and sickle cell disease. Several monoclonal antibodies targeting autoimmune diseases are awaiting FDA approval., Conclusion: Several new novel drugs in the pipeline are intended for use in treating cancers, autoimmune conditions, and rare diseases such as sickle cell disease., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The approval process for pharmaceuticals has always included a consideration of the trade-offs between benefits and risks. Until recently, these trade-offs have been made in panel discussions without using a decision model to explicitly consider what these trade-offs might be. Recently, the EMA and the FDA have embraced Multi-Criteria Decision Analysis (MCDA) as a methodology for making approval decisions. MCDA offers an approach for improving the quality of these decisions and, in particular, by using quantitative and qualitative data in a structured decision model to make trade-offs in a logical, transparent and auditable way. This paper will review the recent use of MCDA by the FDA and EMA and recommend its wider adoption by other National Regulatory Authorities (NRAs) and the pharmaceutical industry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chisholm, Sharry and Phillips.)

Aims: The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) produce guidelines for the design of pivotal psychiatric drug trials used in new drug applications. It is unknown who are involved in the guideline development and what specific trial design recommendations they give., Methods: Cross-sectional study of EMA Clinical Efficacy and Safety Guidelines and FDA Guidance Documents. Study outcomes: (1) guideline committee members and declared conflicts of interest; (2) guideline development and organisation of commenting phases; (3) categorisation of stakeholders who comment on draft and final guidelines according to conflicts of interest ('industry', 'not-industry but with industry-related conflicts', 'independent', 'unclear'); and (4) trial design recommendations (trial duration, psychiatric comorbidity, 'enriched design', efficacy outcomes, comparator choice). Protocol registration https://doi.org/10.1101/2020.01.22.20018499 (27 January 2020)., Results: We included 13 EMA and five FDA guidelines covering 15 psychiatric indications. Eleven months after submission, the EMA had not processed our request regarding committee member disclosures. FDA offices draft the Guidance Documents, but the Agency is not in possession of employee conflicts of interest declarations because FDA employees generally may not hold financial interests (although some employees may hold interests up to $15,000). The EMA and FDA guideline development phases are similar; drafts and final versions are publicly announced and everybody can submit comments. Seventy stakeholders commented on ten guidelines: 38 (54%) 'industry', 18 (26%) 'not-industry but with industry-related conflicts', six (9%) 'independent' and eight (11%) 'unclear'. They submitted 1014 comments: 640 (68%) 'industry', 243 (26%) 'not-industry but with industry-related conflicts', 44 (5%) 'independent' and 20 (2%) 'unclear' (67 could not be assigned to a specific stakeholder). The recommended designs were generally for trials of short duration; with restricted trial populations; allowing previous exposure to the drug; and often recommending rating scale efficacy outcomes. EMA mainly recommended three arm designs (both placebo and active comparators), whereas FDA mainly recommended placebo-controlled designs. There were also other important differences and FDA's recommendations regarding the exclusion of psychiatric comorbidity seemed less restrictive., Conclusions: The EMA and FDA clinical research guidelines for psychiatric pivotal trials recommend designs that tend to have limited generalisability. Independent and non-conflicted stakeholders are underrepresented in the guideline development. It seems warranted with more active involvement of scientists and independent organisations without conflicts of interest in the guideline development process.

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation., Methods: Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM ® MarketScan ® Commercial and Medicare Supplemental US insurance claims databases (March 2016-October 2018). Second, using data collected in the Corrona US RA Registry (February 2016-August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions., Results: In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses., Conclusion: These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA., Trial Registration: Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020.

Today's surge of big data coming from multiple sources is raising the stakes that pharmacovigilance has to win, making evidence synthesis a more and more robust approach in the field. In this scenario, many scholars believe that new computational methods derived from data mining will effectively enhance the detection of early warning signals for adverse drug reactions, solving the gauntlets that post-marketing surveillance requires. This article highlights the need for a philosophical approach in order to fully realize a pharmacovigilance 2.0 revolution. A state of the art on evidence synthesis is presented, followed by the illustration of E-Synthesis , a Bayesian framework for causal assessment. Computational results regarding dose-response evidence are shown at the end of this article.

Cell-based medicinal products (CBMPs), a category of advanced-therapy medicinal products (ATMPs), are authorised for the European market by the European Commission by means of the centralized marketing authorisation. By conforming to the German Medicinal Products Act (Sec. 4b AMG), national authorisation can be granted by the Paul-Ehrlich-Institut in Germany exclusively for ATMPs not based on a routine manufacturing procedure. In both procedures, quality, efficacy, and safety are evaluated and the risk-benefit balance is assessed. For the centralised procedure, mainly controlled clinical trial data must be submitted, whereas the requirements for national procedures could be modified corresponding to the stage of development of the ATMP. After marketing authorization, the marketing authorization/license holder is obligated to report all serious adverse reactions to the competent authority and to provide periodic safety update reports. If necessary, post-authorization safety studies could be imposed. On the basis of these regulatory measures, the safety of advanced therapies can be monitored and improved.

Introduction: Prior studies suggested that holding preinvestigational new drug application (PIND) meetings with FDA has a positive effect on clinical development time (CDT)., Methods: New product marketing applications submitted to FDA CDER during fiscal years 2008-2012 were assessed for whether a PIND meeting was held and, if so, a qualitative assessment of meeting content was performed., Results: Discussions contained in the PIND meeting minutes tended to reflect topics appropriate to an early phase of drug development, including chemistry, manufacturing, and controls (CMC) and safety topics (eg, nonclinical and clinical domains). Additionally, FDA commonly provided additional advice most often in the clinical and CMC domains. Applications for which a PIND meeting was held during drug development had shorter CDTs than those that did not., Conclusions: This analysis showed the importance of early communication with FDA during development, and small companies with limited regulatory experience may gain the greatest benefit from early communication with FDA.

The goal of this article is to help practitioners understand the regulatory framework and basis for the approval of new animal drugs, the terminology and specific meaning of terms related to drug approval, and the marketing and use of veterinary drugs in companion animal practice. Understanding the differences between approved versus unapproved drugs and their use helps practitioners make the appropriate clinical decisions on their patients' treatment. Only when buying approved animal drugs can clinicians be assured of product safety, effectiveness, and manufacturing to the strict standards for quality, purity, and potency, as well as truthful and complete labeling., (Published by Elsevier Inc.)