Drugs

Veronese, Nicola; Cooper, Cyrus; Bruyère, Olivier; Al-Daghri, Nasser M.; Branco, Jaime; Cavalier, Etienne; Cheleschi, Sara; da Silva Rosa, Mario Coelho; Conaghan, Philip G.; Dennison, Elaine M.; de Wit, Maarten; Fioravanti, Antonella; Fuggle, Nicholas R.; Haugen, Ida K.; Herrero-Beaumont, Gabriel; Honvo, Germain; Laslop, Andrea; Matijevic, Radmila; Migliore, Alberto; Mobasheri, Ali; Pelletier, Jean-Pierre; Prieto Yerro, María Concepción; Radermecker, Régis Pierre; Rannou, François; Rizzoli, René; Reginster, Jean-Yves

doi: 10.1007/s40265-022-01773-5pmid: 36112341

Knee osteoarthritis (OA) is one of the most common and disabling medical conditions. In the case of moderate to severe pain, a single intervention may not be sufficient to allay symptoms and improve quality of life. Examples include first-line, background therapy with symptomatic slow-acting drugs for OA (SYSADOAs) or non-steroidal anti-inflammatory drugs (NSAIDs). Therefore, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) performed a review of a multimodal/multicomponent approach for knee OA therapy. This strategy is a particularly appropriate solution for the management of patients affected by knee OA, including those with pain and dysfunction reaching various thresholds at the different joints. The multimodal/multicomponent approach should be based, firstly, on different combinations of non-pharmacological and pharmacological interventions. Potential pharmacological combinations include SYSADOAs and NSAIDs, NSAIDs and weak opioids, and intra-articular treatments with SYSADOAs/NSAIDs. Based on the available evidence, most combined treatments provide benefit beyond single agents for the improvement of pain and other symptoms typical of knee OA, although further high-quality studies are required. In this work, we have therefore provided new, patient-centered perspectives for the management of knee OA, based on the concept that a multimodal, multicomponent, multidisciplinary approach, applied not only to non-pharmacological treatments but also to a combination of the currently available pharmacological options, will better meet the needs and expectations of patients with knee OA, who may present with various phenotypes and trajectories.

Mercadante, Sebastiano

doi: 10.1007/s40265-022-01780-6pmid: 36129661

Management of cancer pain is challenging. Despite the poor evidence, opioid therapy still remains the cornerstone for the management of cancer-related pain. Opioids should be given according to the clinical presentation in the different stages of disease. There is no drug of choice, as most opioids are effective. Thus, the choice should be based on the individual characteristics of patients. Optimization of opioid therapy may allow individual treatment according to the patient’s characteristics and pain syndromes, providing timely alternatives in the different stages of disease. While most patients respond to an appropriate treatment associated with a comprehensive assessment and symptom control, a high level of experience and knowledge is necessary in determining conditions to maximize the analgesic response, eventually adding adjuvants in some specific circumstances. Alternative opioids may improve the balance between analgesia and adverse effects in the presence of a poor response to the first opioid in a large number of patients. Finally, a selected population can benefit from some interventional procedures.

Johnson, Stephen A.; Fang, Ton; De Marchi, Fabiola; Neel, Dylan; Van Weehaeghe, Donatienne; Berry, James D.; Paganoni, Sabrina

doi: 10.1007/s40265-022-01769-1pmid: 36121612

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder involving loss of upper and lower motor neurons, with most cases ending in death within 3–5 years of onset. Several molecular and cellular pathways have been identified to cause ALS; however, treatments to stop or reverse disease progression are yet to be found. Riluzole, a neuroprotective agent offering only a modest survival benefit, has long been the sole disease-modifying therapy for ALS. Edaravone, which demonstrated statistically significant slowing of ALS disease progression, is gaining approval in an increasing number of countries since its first approval in 2015. Sodium phenylbutyrate and taurursodiol (PB-TURSO) was conditionally approved in Canada in 2022, having shown significant slowing of disease progression and prolonged survival. Most clinical trials have focused on testing small molecules affecting common cellular pathways in ALS: targeting glutamatergic, apoptotic, inflammatory, and oxidative stress mechanisms among others. More recently, clinical trials utilizing stem cell transplantation and other biologics have emerged. This rich and ever-growing pipeline of investigational products, along with innovative clinical trial designs, collaborative trial networks, and an engaged ALS community’, provide renewed hope to finding a cure for ALS. This article reviews existing ALS therapies and the current clinical drug development pipeline.

Li, Josephine H.; Florez, Jose C.

doi: 10.1007/s40265-022-01774-4pmid: 36123514

The epidemic of type 2 diabetes (T2D) is a significant global public health challenge and a major cause of morbidity and mortality. Despite the recent proliferation of pharmacological agents for the treatment of T2D, current therapies simply treat the symptom, i.e. hyperglycemia, and do not directly address the underlying disease process or modify the disease course. This article summarizes how genomic discovery has contributed to unraveling the heterogeneity in T2D, reviews relevant discoveries in the pharmacogenetics of five commonly prescribed glucose-lowering agents, presents evidence supporting how pharmacogenetics can be leveraged to advance precision medicine, and calls attention to important research gaps to its implementation to guide treatment choices.

Fung, Simon; Syed, Yahiya Y.

doi: 10.1007/s40265-022-01763-7pmid: 36018461

Triamcinolone acetonide injectable suspension for suprachoroidal use (Xipere®; SCS triamcinolone acetonide) is a corticosteroid approved in the USA for the treatment of macular edema associated with uveitis. Suprachoroidal injection of SCS triamcinolone acetonide results in preferential distribution into the posterior segment, which may reduce the risk of corticosteroid-related adverse events, such as cataracts and intraocular pressure (IOP) elevation. In a multicenter phase III trial in patients with non-infectious uveitic macular edema, SCS triamcinolone acetonide significantly and rapidly improved visual acuity and reduced signs of macular edema compared with sham treatment. SCS triamcinolone acetonide was generally well tolerated, with the most common adverse event being eye pain on the day of the procedure. The risk of corticosteroid-related IOP elevation appeared to be reduced in unrescued patients in the SCS triamcinolone acetonide group compared with patients in the sham control group who received rescue therapy. SCS triamcinolone acetonide is a novel and useful treatment option for uveitic macular edema.

Fung, Simon; Syed, Yahiya Y.

doi: 10.1007/s40265-022-01777-1pmid: 36074323

Hoy, Sheridan M.

doi: 10.1007/s40265-022-01764-6pmid: 35986838

Pimitespib (Jeselhy®) is an oral small molecule inhibitor of the α and β isoforms of heat shock protein 90 (HSP90). HSP90α and HSP90β regulate the stability and activity of a number of proteins that are crucial for tumour development. Pimitespib is being developed by Taiho Pharmaceutical for the treatment of solid tumours, including gastrointestinal stromal tumour (GIST), and in June 2022 it received its first approval in Japan for GIST that has progressed after chemotherapy. Pimitespib is undergoing phase I development for the treatment of solid tumours in the EU and the USA. This article summarizes the milestones in the development of pimitespib leading to this first approval for GIST that has progressed after chemotherapy.

Keam, Susan J.

doi: 10.1007/s40265-022-01765-5pmid: 35997942

Vutrisiran (AMVUTTRA™) is a subcutaneously administered transthyretin-directed small interfering ribonucleic acid (siRNA) therapeutic (also called RNA interference, or RNAi therapeutic) being developed by Alnylam Pharmaceuticals, Inc. for the treatment of amyloid transthyretin-mediated (ATTR) amyloidosis, including hereditary ATTR (hATTR) amyloidosis and wild-type ATTR (wtATTR) amyloidosis. Vutrisiran was approved in June 2022 in the USA for the treatment of the polyneuropathy of hATTR amyloidosis in adults and received a positive opinion in the EU in July 2022 for the treatment of hATTR amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy. Vutrisiran is also under regulatory review for the treatment of the polyneuropathy of hATTR amyloidosis in adults in Japan and Brazil. This article summarizes the milestones in the development of vutrisiran leading to this first approval in hATTR amyloidosis.

Keam, Susan J.

doi: 10.1007/s40265-022-01775-3pmid: 36103022

Eladocagene exuparvovec (Upstaza™) is a gene therapy developed by PTC Therapeutics for the treatment of human aromatic L-amino acid decarboxylase (AADC) deficiency. Eladocagene exuparvovec comprises an adeno-associated virus vector that delivers the dopa decarboxylase (DDC) gene, the gene for human AADC. Eladocagene exuparvovec was approved in July 2022 in the EU for the treatment of patients aged 18 months and older with a clinical, molecular, and genetically confirmed diagnosis of AADC deficiency with a severe phenotype (i.e. patients who cannot sit, stand or walk). This article summarizes the milestones in the development of eladocagene exuparvovec leading to this first approval for the treatment of patients aged 18 months and older with AADC deficiency.

Keam, Susan J.

doi: 10.1007/s40265-022-01771-7pmid: 36040637