Donanemab: First Approval.

Donanemab (donanemab-azbt; KisunlaTM) is an amyloid ß-directed antibody developed by Eli Lilly and Company for the treatment of Alzheimer's disease. Donanemab recently received approval in the USA for the treatment of adults with early symptomatic Alzheimer's disease (patients with mild cognitive impairment or mild dementia stage of disease). This article summarizes the milestones in the development of donanemab leading to this first approval for Alzheimer's disease.

Sotatercept: First Approval.

Sotatercept (sotatercept-csrk; WINREVAIRTM) is an activin signalling inhibitor that is being developed by Merck and Co., Inc. (Rahway, NJ, USA) for the treatment of pulmonary arterial hypertension. Sotatercept recently received approval in the USA for the treatment of adults with pulmonary arterial hypertension [World Health Organisation (WHO) Group 1] to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events. This article summarizes the milestones in the development of sotatercept leading to this first approval for pulmonary arterial hypertension.

Alirocumab: Pediatric First Approval.

Alirocumab (Praluent®), a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor that has been co-developed by Regeneron Pharmaceuticals, Inc. and Sanofi (formerly sanofi-aventis), is approved globally for use in adults with established cardiovascular disease, primary hyperlipidemia [including heterozygous familial hypercholesterolemia (HeFH) or homozygous familial hypercholesterolemia (HoFH)]. In November 2023, based on clinical data in patients aged 8-17 years, alirocumab received its first pediatric approval in the EU as an adjunct to diet alone, or in combination with a statin and/or other low-density lipoprotein cholesterol (LDL-C)-lowering therapies, in pediatric patients aged ≥ 8 years with HeFH. Alirocumab was approved a few months later in the US for use as an adjunct to diet and other LDL-C-lowering therapies in pediatric patients aged ≥ 8 years with HeFH to reduce LDL-C. This article summarizes the milestones in the development of alirocumab leading to this first pediatric approval for HeFH.

Impact of a Mock OSCE on Student Confidence in Applying the Pharmacists' Patient Care Process.

The Medical and Pharmacy Student Collaboration (MAPSC) student organization at the University of Southern California, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, created an extracurricular, peer-led, virtual group mock objective structured clinical examination (MOSCE) to expose first-year pharmacy students (P1s) to the Pharmacists' Patient Care Process (PPCP). The purpose of this study is to evaluate the impact of a MAPSC MOSCE on P1s self-reported confidence in applying the PPCP and on patient communication, medication knowledge, and clinical skills. An anonymous, optional, self-reported survey was administered to P1s before and after the event, where they rated their confidence on a scale of 0-100 (0 = not confident, 100 = certainly confident). The statistical analysis was a paired two-tailed t-test with a significance level of p < 0.05. A total of 152 P1s and 30 facilitators attended the MOSCE. One hundred thirty-nine students met the inclusion criteria and were included in the data analysis. There was a statistically significant difference in the change in self-reported confidence for all PPCP components and learning outcomes. The results of our study strongly indicate that introducing P1 students to the PPCP through a MAPSC MOSCE format is a valuable experience.

Ruxolitinib Cream 1.5%: A Review in Non-Segmental Vitiligo.

Topical ruxolitinib 1.5% cream (Opzelura®), a Janus kinase (JAK) inhibitor, is the first treatment to be approved in several countries for use in patients aged ≥ 12 years with non-segmental vitiligo. In the identical phase III TRuE-V1 and TRuE-V2 trials, significantly more ruxolitinib cream recipients were able to achieve statistically significant and clinically meaningful facial and total body repigmentation, as well as reductions in vitiligo noticeability, compared with vehicle recipients. Efficacy was sustained in longer-term analyses to week 104 of treatment. Ruxolitinib 1.5% cream was generally tolerable in these trials; the most common treatment-related adverse events were acne, pruritus and exfoliation, all at the application site. As with orally administered JAK inhibitors, topical ruxolitinib carries boxed warnings in the USA for serious infections, mortality, malignancy, major adverse cardiovascular events (MACE) and thrombosis, although the incidences were low with topical application. Thus, topical ruxolitinib 1.5% cream is an effective and generally tolerable treatment option for patients aged ≥ 12 years with non-segmental vitiligo.

Non-segmental vitiligo is a chronic autoimmune disease where the skin throughout the body loses its pigmentation, and is usually managed with topical therapies, light therapy or surgery. Topical ruxolitinib 1.5% cream (Opzelura^®) is the first treatment approved in several countries for patients aged ≥ 12 years with non-segmental vitiligo. It inhibits Janus kinase (JAK) proteins, reducing the destruction of skin pigment-producing cells. In two clinical trials, significantly more ruxolitinib cream recipients achieved significant and meaningful skin repigmentation compared with patients who received a non-medicated cream; these results were sustained to week 104 of treatment. Ruxolitinib 1.5% cream was generally tolerable; the most common treatment-related adverse events were acne, itchiness and exfoliation, all at the application site. Topical ruxolitinib has special warnings in the USA for major adverse cardiovascular events (MACE), blood clots, serious infections, death and cancer (associated with the use of oral JAK inhibitors), although incidence rates for these adverse events were low in the clinical trials. Topical ruxolitinib 1.5% cream is an effective and generally tolerable treatment option for patients aged ≥ 12 years with non-segmental vitiligo.

Sacituzumab Govitecan: A Review in Unresectable or Metastatic HR+/HER2- Breast Cancer.

Sacituzumab govitecan (TRODELVY®) is a first-in-class trophoblast cell-surface antigen 2 (Trop-2)-directed antibody and topoisomerase I inhibitor conjugate that is approved globally as monotherapy for the treatment of adults with unresectable locally advanced or metastatic, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-; defined as immunohistochemistry 0, 1+ or 2+ and in situ hybridization-negative) breast cancer who have received endocrine-based therapy and ≥ 2 additional systemic therapies in the advanced setting. In the phase III TROPiCS-02 trial, intravenous sacituzumab govitecan demonstrated statistically significant and clinically meaningful improvements in progression-free survival and overall survival compared with physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) in adults with metastatic HR+/HER2- breast cancer. Sacituzumab govitecan had a generally manageable tolerability profile in these patients; the most common treatment-related grade ≥ 3 adverse events included neutropenia, diarrhoea, leukopenia, anaemia, fatigue and febrile neutropenia. Sacituzumab govitecan carries regulatory warnings for severe neutropenia and severe diarrhoea. Sacituzumab govitecan demonstrated an overall benefit in terms of health-related quality of life. Current evidence indicates that sacituzumab govitecan is an effective treatment option, with a generally manageable tolerability profile, for patients with pre-treated, unresectable locally advanced or metastatic HR+/HER2- breast cancer.

The most common type of breast cancer is hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−), and management of metastatic (spread to areas near the breast or to other areas) HR+/HER2− breast cancer eventually requires chemotherapy or surgery if resistance develops. Intravenous sacituzumab govitecan (TRODELVY^®) is approved globally for adults with inoperable or metastatic HR+/HER2− breast cancer who have previously received endocrine therapy and ≥ 2 additional systemic therapies for advanced disease. In a clinical trial, sacituzumab govitecan therapy significantly improved the duration adults with metastatic HR+/HER2− breast cancer survived without their disease progressing, along with overall survival time, versus standard chemotherapy. The tolerability profile of sacituzumab govitecan was generally manageable; the most common side effects were decreased neutrophil count, diarrhoea and decreased white blood cell count. Sacituzumab govitecan can severely reduce neutrophil count and cause severe diarrhoea. Sacituzumab govitecan demonstrated an overall benefit in terms of health-related quality of life. Current evidence indicates that sacituzumab govitecan is an effective treatment option, with a generally manageable tolerability profile, for patients with pre-treated, inoperable or metastatic HR+/HER2− breast cancer.

Danicopan: First Approval.

Danicopan (Voydeya®) is an oral complement factor D inhibitor that is being developed by Alexion AstraZeneca Rare Disease as add-on treatment to ravulizumab or eculizumab for patients with clinically significant extravascular haemolysis. Danicopan recently received approval in Japan for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH) when used in addition to a complement component 5 (C5) inhibitor. Subsequently, the European Medicines Agency adopted a positive opinion recommending the granting of marketing authorisation for danicopan for the treatment of patients with PNH who continue to have residual haemolytic anaemia despite treatment with a complement C5 inhibitor. This article summarizes the milestones in the development of danicopan leading to this first approval for PNH.

Lumasiran: A Review in Primary Hyperoxaluria Type 1.

Lumasiran (Oxlumo®), a first-in-class synthetic, double-stranded, ribonucleic acid (RNA) interference molecule targeting glycolate oxidase through silencing HAO1 mRNA, is approved in several countries for patients of any age and stage of kidney function with primary hyperoxaluria type 1 (PH1). Approval was based on results from the phase III ILLUMINATE trials. In the double-blind, placebo-controlled, ILLUMINATE-A trial, subcutaneous lumasiran was significantly more effective than placebo in reducing 24-h urinary oxalate excretion in patients aged ≥ 6 years with PH1; this effect was sustained for ≥ 36 months in ongoing longer-term analyses. In the single-arm ILLUMINATE-B trial, lumasiran reduced urinary oxalate:creatinine ratios and plasma oxalate levels in patients aged < 6 years with PH1. In the single-arm ILLUMINATE-C trial, lumasiran reduced plasma oxalate levels in patients with PH1 receiving dialysis as well as those not receiving dialysis. In secondary and exploratory analyses of these trials, nephrocalcinosis grade, kidney stone event rates and estimated glomerular filtration rates were either stable or improved with lumasiran. Lumasiran had an acceptable tolerability profile that remained consistent in longer-term analyses; the most common adverse events were mild and transient injection-site reactions. Thus, lumasiran is an effective treatment option, with an acceptable tolerability profile, in patients with PH1.

Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder that leads to excess oxalate in urine or plasma requiring removal by the kidneys. This overproduction is damaging and can lead to kidney failure. Management of PH1 is typically not curative, eventually ending in kidney and/or liver transplantation. Lumasiran (Oxlumo^®) is the first medicine to be approved in several countries for use in patients with PH1, regardless of their age or level of kidney function. It reduces liver oxalate production, lessening damage to the kidneys and potentially reducing the need for organ transplantation. In clinical trials, lumasiran was effective in reducing oxalate levels (in urine and/or plasma) in patients of all ages with PH1, and irrespective of whether they were receiving dialysis or not. Lumasiran either improved or stabilized the severity of calcium deposition in the kidneys, number of kidney stone events and kidney function. Lumasiran had an acceptable tolerability profile; the most common side effects were mild injection-site reactions that resolved quickly. Thus, lumasiran is an effective treatment option, with an acceptable tolerability profile, in patients with PH1.

Trastuzumab Deruxtecan: A Review in Gastric or Gastro-Oesophageal Junction Adenocarcinoma.

Trastuzumab deruxtecan (Enhertu®) is a human epidermal growth factor receptor type 2 (HER2)-directed antibody-drug conjugate that is approved in several countries globally for adults with advanced HER2-positive gastric or gastro-oesophageal junction (GOJ) adenocarcinoma who have received a prior trastuzumab-based regime. In the phase II DESTINY-Gastric01 trial, intravenous trastuzumab deruxtecan was significantly more effective than standard chemotherapy (physician's choice of intravenous irinotecan or paclitaxel) in achieving objective response and improving overall survival in Japanese or South Korean adults with advanced HER2-positive gastric or GOJ adenocarcinoma who had received two or more previous therapies. In the phase II DESTINY-Gastric02 trial, trastuzumab deruxtecan was able to induce durable response in adults from the USA or Europe with unresectable or metastatic HER2-positive gastric or GOJ adenocarcinoma. Trastuzumab deruxtecan was generally tolerable in these patients; the most common adverse events included nausea, neutropenia, fatigue and decreased appetite. Trastuzumab deruxtecan carries regulatory warnings (including boxed warnings in the USA) for interstitial lung disease/pneumonitis and embryo-foetal toxicity. Current evidence indicates that trastuzumab deruxtecan is an effective treatment option, and is generally tolerable, in previously treated adults with advanced HER2-positive gastric or GOJ adenocarcinoma.

Gastric or gastro-oesophageal junction (GOJ) adenocarcinomas are types of stomach cancer, which is one of the leading causes of cancer-related deaths globally. Some gastric cancers overexpress human epidermal growth factor receptor 2 (HER2), a predictor of relapse and poor survival. Management can involve several options, including surgery, chemotherapy, radiation and other systemic therapies as the first line of treatment. Trastuzumab plus chemotherapy is the standard treatment for patients with HER2-positive (HER2+) gastric or GOJ adenocarcinoma. Intravenously administered trastuzumab deruxtecan (Enhertu^®) is approved in several countries for adults with advanced (spread to areas near the stomach or to other parts of the body) HER2+ gastric or GOJ adenocarcinoma who have previously received a trastuzumab-based treatment. Trastuzumab deruxtecan is cytotoxic and targets HER2-expressing tumour cells. In the DESTINY-Gastric01 trial, trastuzumab deruxtecan was significantly more effective than standard chemotherapy in achieving complete or partial responses and improving overall survival in Japanese or South Korean adults with advanced gastric or GOJ adenocarcinoma. In the DESTINY-Gastric02 trial, trastuzumab deruxtecan was able to induce confirmed (4 weeks after the initial response) complete or partial responses in adults from the USA or Europe with advanced gastric or GOJ adenocarcinoma. Trastuzumab deruxtecan was generally tolerable; the most common adverse events included nausea, decreased neutrophil count, fatigue and decreased appetite. Treatment with trastuzumab deruxtecan can lead to interstitial lung disease/lung inflammation and embryo-foetal toxicity. Current evidence indicates that trastuzumab deruxtecan is an effective treatment option, and is generally tolerable, in previously treated adults with advanced HER2+ gastric or GOJ adenocarcinoma.

Avacincaptad Pegol: First Approval.

Avacincaptad pegol (IZERVAY™; formerly Zimura®) is a complement C5 inhibitor that is being developed by IVERIC Bio, an Astellas company, for the treatment of geographic atrophy secondary to age-related macular degeneration. Avacincaptad pegol recently received approval for the treatment of adults with geographic atrophy secondary to age-related macular degeneration. This article summarizes the milestones in the development of avacincaptad pegol leading to this first approval for geographic atrophy secondary to age-related macular degeneration.

Prescribing Practices for Agitation Medication in Obese Patients Admitted to the Emergency Department.

INTRODUCTION: Weight is a factor that influences the dosages of many medications, although no clinical studies have evaluated this factor in the use of agitation medications in the obese population. The objectives of this study were to assess the need for weight considerations in dosing antipsychotics and benzodiazepines for patients with agitation and to assess prescribing patterns in agitated patients. METHODS: This retrospective cohort study compared outcomes between obese and nonobese adult patients who received at least one parenteral administration of an antipsychotic or benzodiazepine for agitation in the emergency department. The primary outcomes were total antipsychotic and benzodiazepine doses within 24 hours (in chlorpromazine equivalents and lorazepam equivalents, respectively). Key secondary outcomes included antipsychotic and benzodiazepine doses used for first administration, incidence of repeat emergency medication administration within 24 hours, time to next administration, and number of repeat administrations within 24 hours. RESULTS: The study examined 115 patient encounters in each cohort of patients in the study. The baseline characteristics of the 2 study cohorts were similar. Both groups had similar mean 24-hour antipsychotic usage [272.7 chlorpromazine equivalents (nonobese cohort), 313.5 chlorpromazine equivalents (obese cohort); P=0.157] and mean 24-hour benzodiazepine usage [0.9 lorazepam equivalents (both cohorts); P=0.750]. Differences between the study cohorts on all of the secondary outcomes were also not statistically significant (P>0.05). DISCUSSION: This study did not find the use of higher dosages of agitation medication in the obese compared with the nonobese population. Future prospective trials, with possible emphasis on individual medications, specific etiologies of agitation, or morbid obesity, are required to confirm this finding or to elucidate potential differences in optimal medication dosages for the obese population.

Retifanlimab: First Approval.

Retifanlimab (retifanlimab-dlwr; ZYNYZTM) is a programmed cell death 1 receptor-blocking antibody that is being developed by Incyte Corporation for the treatment of solid tumours, both as monotherapy and in combination with other agents. Retifanlimab recently received accelerated approval for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma. This article summarizes the milestones in the development of retifanlimab leading to this first approval for Merkel cell carcinoma.

Ravulizumab: A Review in Generalised Myasthenia Gravis.

Ravulizumab (ULTOMIRIS®) is the first long-acting complement C5 inhibitor (administered intravenously every 8 weeks) to be approved in several countries globally, for adults with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor antibody-positive (AChR Ab+). In the phase III CHAMPION MG trial, intravenous ravulizumab was associated with statistically significant improvements in the MG-Activities of Daily Living scale at week 26 of treatment compared with placebo in adults with AChR Ab+ gMG. Improvements in the Quantitative MG scale total score were also statistically significantly higher in ravulizumab than placebo recipients. These improvements were sustained to week 26 of treatment. Ravulizumab was generally well tolerated; the most common treatment-emergent adverse events were headache, diarrhoea and nausea. Efficacy and tolerability data for up to 1 year from the ongoing open-label extension phase are consistent with those from the randomized, placebo-controlled phase; further results are awaited with interest. Thus, ravulizumab is an efficacious, generally well tolerated and convenient treatment option in adults with AChR Ab+ gMG, expanding the options available for gMG management.

Generalised myasthenia gravis (gMG) is a rare chronic condition that affects the muscles, making them become abnormally tired and weak after use. Prevalence can vary (5.3­35 per 100,000 people) and is steadily rising. Management of gMG can involve modifying or suppressing the immune system, symptom management and/or surgical removal of the thymus gland. Complement C5 inhibitors are another treatment option for patients with gMG. Ravulizumab (ULTOMIRIS^®) is the first long-acting complement C5 inhibitor (administered intravenously every 8 weeks) to be approved in several countries globally for the treatment of adults with gMG who are anti-acetylcholine receptor antibody-positive (AChR Ab+). Ravulizumab is associated with long-lasting improvements in activities of daily living and disease status in adults with AChR Ab+ gMG, as demonstrated in a phase III clinical trial. In this trial, ravulizumab was generally well tolerated; headache, diarrhoea and nausea were the most common adverse events. Although there is a potential risk for adverse reactions with ravulizumab treatment, including serious meningococcal infections, other infections and infusion-related reactions, no meningococcal infections occurred and the incidence of infusion-related reactions was low in patients with gMG. The efficacy and tolerability of ravulizumab were sustained for up to 1 year of treatment; further results are awaited with interest. Thus, ravulizumab is an efficacious, generally well tolerated and convenient treatment option in adults with AChR Ab+ gMG, expanding the options available for gMG management.

Keverprazan Hydrochloride: First Approval.

Keverprazan hydrochloride () is a potassium ion competitive acid blocker that is being developed by Jiangsu Carephar Pharmaceuticals for the treatment of acid-related disease. Keverprazan hydrochloride was recently approved in China for the treatment of adults with reflux oesophagitis or duodenal ulcer. This article summarizes the milestones in the development of keverprazan hydrochloride leading to this first approval for reflux oesophagitis and duodenal ulcer.

Clozapine is the approved option in treatment-resistant schizophrenia and requires careful management.

Clozapine is the only agent approved for treatment-resistant schizophrenia, but is underprescribed. Its adverse drug event (ADE) profile and patient monitoring requirements can discourage its use, but the benefits of clozapine generally outweigh its risks, as most ADEs are manageable. Careful patient assessment, gradual titration, minimum effective dosages, therapeutic drug monitoring and checks of neutrophils, cardiac enzymes and ADE symptoms are recommended. Neutropenia is common but does not necessarily warrant permanent clozapine cessation.

Olutasidenib: First Approval.

Olutasidenib (REZLIDHIATM), an isocitrate dehydrogenase-1 (IDH1) inhibitor, is being developed by Rigel Pharmaceuticals for the treatment of relapsed or refractory (R/R) acute myeloid leukaemia (AML). Olutasidenib was recently approved in the USA for the treatment of adults with R/R AML with a susceptible IDH1 mutation as detected by a US Food and Drug Administration-approved test. This article summarizes the milestones in the development of olutasidenib leading to this first approval for R/R AML.

Teclistamab: First Approval.

Teclistamab (TECVAYLI®), a bispecific antibody that targets CD3 and B cell maturation antigen (BCMA), is being developed by Janssen Research and Development for the treatment of relapsed or refractory multiple myeloma. Teclistamab was recently granted conditional approval in the EU for the treatment of adult patients with relapsed and refractory multiple myeloma who have received three or more prior therapies (including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody) and have demonstrated disease progression on the last therapy. Teclistamab was subsequently approved in the US for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy (including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody). This article summarizes the milestones in the development of teclistamab leading to this first approval for relapsed or refractory multiple myeloma.