Drugs of Today

Osteoporosis is a chronic disease with high unmet medical need. It is characterized by low bone mass and deteriorated bone architecture, leading to increased risk of fragility fractures, with vertebral and hip fractures representing the highest risk of morbidity and mortality. The baseline therapeutic approach to osteoporosis treatment has been based on adequate intake of calcium and supplementation of vitamin D. In this review, we focus on two approved monoclonal antibodies, romosozumab and denosumab, which have been shown to be efficient and safe options to prevent patient fractures...

On January 25, 2022, the U.S. Food and Drug Administration (FDA) approved the use of tebentafusp, a bispecific glycoprotein 100 (gp100) peptide-human leukocyte antigen (HLA)-directed CD3 T-cell activator, for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Pharmacodynamic data indicate that tebentafusp targets a specific HLA-A*02:01/gp100 complex, activating both CD4+/CD8+ effector and memory T cells that induce tumor cell death. Tebentafusp is administered to patients via intravenous infusion daily or weekly, depending on the indication...

Nearly two-thirds of patients with non-small cell lung cancer (NSCLC) have locally advanced or metastatic disease at the time of diagnosis, and many patients with early-stage disease will eventually experience metastatic recurrence. In the absence of a known driver alteration, treatment of metastatic NSCLC is limited to immunotherapy with or without cytotoxic chemotherapy. For most patients with locally advanced unresectable NSCLC, the standard of care involves concurrent chemoradiation followed by consolidative immunotherapy...

In recent years, the role of interleukin-17 (IL-17) in orchestrating and manipulating proinflammatory immune responses has received special attention. It has become apparent from murine studies and clinical trials that due to its inhibitory effect on immunoregulation and its stimulatory action on promoting proinflammatory responses, IL-17 is an ideal cytokine to target for drug development, in order to cease its induction or eliminate IL-17-producing cells of any kind. Several monoclonal antibodies have been developed and tested as potent inhibitors of IL-17 in various inflammatory diseases...

Mitapivat, an oral first-in-class activator of erythrocyte pyruvate kinase (PKR), was first investigated in patients with pyruvate kinase deficiency (PKD), where it was found to improve hemoglobin (Hb) concentrations in patients who did not regularly receive transfusions and to reduce transfusion burden in patients who receive regular transfusions. It was approved in 2022 for the treatment of PKD and is being explored in other hereditary chronic conditions that are associated with hemolytic mechanisms of anemia, such as sickle cell disease (SCD) and thalassemia...

Dry eye disease (DED) is the most common ocular surface disorder affecting millions of people worldwide. Due to its chronic nature, the management of DED still represents a challenge in the ophthalmic practice. Nerve growth factor (NGF), which is expressed along with its high-affinity TrkA receptor on the ocular surface complex, has been widely studied for the treatment of neurotrophic keratopathy, and a novel recombinant human NGF (rhNGF) has recently received full market authorization in this setting. Since NGF has shown in both in vitro and in vivo studies to promote corneal healing, to enhance conjunctival epithelium differentiation and mucin secretion, and to stimulate tear film production and functionality, it could provide potential benefits also in patients with DED...

On November 8, 2022, the United States Food and Drug Administration (FDA) issued an emergency use authorization for the interleukin-1 (IL-1) inhibitor anakinra for the treatment of patients with COVID-19 pneumonia. The authorization was specifically intended for patients requiring supplemental oxygen who are at risk of progression to respiratory failure and are likely to have an elevated plasma soluble urokinase plasminogen activator receptor. Anakinra is a modified, recombinant human IL-1 receptor antagonist used to treat rheumatoid arthritis, neonatal-onset multisystem inflammatory disease and other inflammatory diseases...

Melanoma is a highly lethal type of skin cancer. Although an early diagnosis, in combination with surgery for nonmetastatic melanomas, significantly increases the probability of survival, there are no efficacious treatments for metastatic melanoma. Nivolumab and relatlimab are monoclonal antibodies that selectively interact with and block the proteins programmed cell death protein 1 (PD-1) and lymphocyte activation protein 3 (LAG-3), respectively, and thus, their activation by their cognate ligands. The combination of these immunotherapy drugs was approved in 2022 by the United States Food and Drug Administration (FDA) for the treatment of melanoma...

Hepatocellular carcinoma (HCC) is a global healthcare problem, with a high prevalence in nonindustrialized countries and a rising incidence in industrialized countries. Sorafenib demonstrated its efficacy as the first therapeutic agent for unresectable HCC in 2007. Since then, other multitarget tyrosine kinase inhibitors have demonstrated efficacy in HCC patients. Still, the tolerability of these drugs remains an unsolved problem, with 5-20% of patients permanently discontinuing their therapies due to adverse events...

Clascoterone is a novel topical antiandrogen medication approved for the treatment of acne. Conventional oral antiandrogen treatments targeting acne such as combined oral contraceptives and spironolactone exert systemic hormonal effects which commonly preclude their usage in male patients while hampering their application in certain female patients. In contrast, clascoterone is a first-in-class antiandrogen proven to be both safe and effective for female and male patients above the age of 12. Outside of occasional localized skin irritation, clascoterone is usually well tolerated, however, some adolescents in a phase II clinical trial experienced biochemical evidence of HPA suppression, which resolved after discontinuing treatment...

Metachromatic leukodystrophy (MLD) is a rare autosomal recessive disorder of sphingolipid metabolism, due to a deficiency of the enzyme arylsulfatase A (ARSA). The main clinical signs of the disease are secondary to central and peripheral nervous system demyelination. MLD is subdivided into early- and late-onset subtypes based upon the onset of neurological disease. The early-onset subtype is associated with a more rapid progression of the disease that leads to death within the first decade of life. Until recently, no effective treatment was available for MLD...

Systemic lupus erythematosus is a complex autoimmune disease with variable disease presentation and progression. Hydroxychloroquine and corticosteroids are first-line therapies. Disease severity and organ system involvement guide escalation of immunomodulatory medications beyond these mainstays. Anifrolumab is a first-in-class global type 1 interferon inhibitor recently approved by the United States Food and Drug Administration (FDA) for systemic lupus erythematosus in addition to standard of care. This article reviews the role of type 1 interferons in lupus pathophysiology and the evidence leading to anifrolumab's approval with particular emphasis on the MUSE, TULIP-1 and TULIP-2 trials...

The Organization for Professionals in Regulatory Affairs (TOPRA) celebrated its 2022 Annual Symposium, which took place in Vienna, Austria, from October 17 to 19, 2022, to discuss most relevant current issues and debate the future of healthcare regulatory affairs for medicinal products, medical devices/in vitro diagnostics (IVDs) and veterinary medicines.

On March 23, 2022, the U.S. Food and Drug Administration (FDA) approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan), also known as 177Lu-PSMA-617, for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who have highly expressed prostate-specific membrane antigen (PSMA) and have at least one metastatic lesion. It is the first FDA-approved targeted radioligand therapy for eligible men with PSMA-positive mCRPC. Lutetium Lu 177 vipivotide tetraxetan is a radioligand that strongly binds to PSMA, making it ideal for treating cancers of the prostate by targeted radiation, resulting in DNA damage and cell death...

Savolitinib is a highly selective MET tyrosine kinase inhibitor. MET is involved in numerous cellular processes such as proliferation, differentiation and the formation of distant metastases. MET amplification and MET overexpression are quite common in many cancers, but MET exon 14 skipping alteration is most common in non-small cell lung cancer (NSCLC). The role of MET signaling as a bypass pathway in the development of acquired resistance to tyrosine kinase inhibitor (TKI) epidermal growth factor receptor (EGFR) therapy in cancer patients with EGFR gene mutation was documented...

While treatment options for multiple myeloma (MM) are continuing to expand, this disease remains one characterized by requiring multiple lines of therapy, with generally decreasing effectiveness of each subsequent line. The development of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy has proven an exception to this rule. In the trial that led to approval of the BCMA CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel) by the U.S. Food and Drug Administration (FDA), deep and durable response rates were observed in heavily pretreated patients...

The SARS-COV-2 pandemic has been a global public health problem since 2019, with over 400 million reported cases, 6 million deaths, and significant economic and social damage. Overlapping SARS-CoV-2 infection in patients with chronic diseases, such as multiple sclerosis (MS), causes management problems, especially in patients treated with disease-modifying therapies. Studies investigating COVID-19 vaccination effectiveness have shown variability in postvaccination immune response that depends on the patient's background treatment, and special attention is required for anti-CD20 therapies...

The epithelium, once simply considered a protective barrier against harmful agents, has in recent times gained considerable relevance as an entity that can promote and regulate inflammatory processes through the production of cytokines, namely interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP), known as "alarmins". TSLP, in particular, has been extensively studied as a possible therapeutic target in patients with severe asthma because it is involved in the inflammatory processes of both type 2-high and type 2-low inflammation...

Myelofibrosis is a rare progressive cancer of the bone marrow that disrupts the normal production of healthy blood cells, leading to bone marrow failure. Patients with myelofibrosis and severe thrombocytopenia (platelet count below 50 × 109 /L) have a wide range of unmet medical needs compared with those without thrombocytopenia. Usually, these patients have an increased disease burden, increased transfusion dependence, shorter overall survival, and limited treatment options. Pacritinib is a new oral kinase inhibitor specifically targeting Janus kinase 2 (JAK2), interleukin-1 receptor-associated kinase 1 (IRAK-1) and colony-stimulating factor 1 receptor (CSF-1R), and is indicated for the treatment of adults with moderate or high risk of primary or secondary myelofibrosis (post-polycythemia or post-primary thrombocytopenia) whose platelet count is less than 50 × 109 /L...

Cabotegravir, a novel HIV integrase inhibitor, shares structural similarity with dolutegravir and bictegravir. Its oral half-life is 32 hours, but cabotegravir nanosuspension for intramuscular injection yields half-lives ranging from 25 to 54 days, enabling extended interval dosing. Drug interactions are minimal, although oral doses require spacing from polyvalent cations, and potent uridine glucuronosyltransferase induction (e.g., rifampin, carbamazepine) requires avoidance due to anticipated subtherapeutic cabotegravir exposure through extended intervals...