Bimekizumab: A Review in Psoriatic Arthritis.

Although several biological disease-modifying antirheumatic drugs (bDMARDs), including interleukin (IL)-17A inhibitors, are approved for psoriatic arthritis, the treatment of this disease remains suboptimal. Bimekizumab (Bimzelx®), a dual IL-17A and IL-17F inhibitor, is approved in the EU, Great Britain and Japan for the treatment of psoriatic arthritis. In pivotal phase 3 clinical trials in patients who were bDMARD-naïve or previously had an inadequate response or intolerance to tumour necrosis factor (TNF) α inhibitors, bimekizumab improved the signs and symptoms of psoriatic arthritis across a range of joint, skin, radiographic and patient-reported outcomes compared with placebo, including the proportion of patients achieving a ≥ 50% response in the American College of Rheumatology criteria. Phase 2 clinical trial data have shown that responses are maintained up to 3 years. Bimekizumab was generally well tolerated in patients with psoriatic arthritis, with a safety profile consistent with that in other approved indications. The most common adverse events included nasopharyngitis, upper respiratory tract infection, oral candidiasis, headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis.

Psoriatic arthritis is a chronic, painful, inflammatory condition that can involve peripheral and axial joints, skin and nails, and can lead to structural joint damage. Several disease-modifying antirheumatic drugs (DMARDs), including biologicals (bDMARDs) that target various inflammatory cytokines, are approved for psoriatic arthritis. However, many patients do not respond or lose response to these treatments. Bimekizumab (Bimzelx^®), an inhibitor of both interleukin (IL)-17A and IL-17F, is approved for the treatment of psoriatic arthritis in the EU, Great Britain and Japan. In clinical trials, bimekizumab improved the signs and symptoms of psoriatic arthritis across key disease domains compared with placebo, including the proportion of patients achieving ≥ 50% response in the American College of Rheumatology criteria. Bimekizumab was efficacious whether patients were naïve to bDMARDs or previously had an inadequate response to or did not tolerate tumour necrosis factor (TNF) α inhibitors. Clinical responses were sustained long-term (up to 3 years). Bimekizumab was generally well tolerated, with the most common adverse events being infections (such as nasopharyngitis, upper respiratory tract infection and oral candidiasis), headache and diarrhoea. In conclusion, bimekizumab extends the treatment options available to patients with psoriatic arthritis.

PB006: A Natalizumab Biosimilar.

PB006 (Tyruko®) is the first biosimilar of the reference monoclonal anti-α4-integrin antibody natalizumab. It is approved for use in the same indications for which reference natalizumab is approved, as a single disease-modifying therapy in adults with highly active relapsing-remitting multiple sclerosis (RRMS). PB006 has similar physicochemical and pharmacodynamic properties to those of reference natalizumab, and the pharmacokinetic similarity of the agents has been demonstrated in a study in healthy subjects. PB006 demonstrated clinical efficacy similar to that of reference natalizumab in patients with RRMS, and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of PB006 were similar to those of reference natalizumab, and switching from reference natalizumab to PB006 appeared to have no impact on tolerability or immunogenicity. The role of reference natalizumab in the management of RRMS is well established and PB006 provides an effective biosimilar alternative for patients requiring natalizumab therapy.

Vonoprazan: A Review in Helicobacter pylori Infection.

Treatment for the eradication of Helicobacter pylori infection, a leading cause of peptic ulcer disease and an important risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma, is indicated whenever infection is identified. However, treatment success rates with current guideline-recommended proton-pump inhibitor (PPI)-based regimens remain suboptimal, with one potential factor associated with treatment failure being inadequate acid suppression. Vonoprazan (Voquezna®) is a first-in-class potassium-competitive acid blocker with the potential to provide potent and sustained acid suppression. Following clinical trials conducted mainly in Asia (supported by post-marketing experience from Asia) and the phase III PHALCON-HP trial conducted in the USA and Europe, vonoprazan is now approved in the USA for use in combination with amoxicillin (dual therapy) or amoxicillin and clarithromycin (triple therapy) for the treatment of H. pylori infection in adults. The vonoprazan-based dual and triple therapy regimens were generally well tolerated in PHALCON-HP. In addition, vonoprazan has advantages including a rapid onset of action and no food effect, making vonoprazan-based dual and triple therapy regimens valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.

Infection with the bacterium Helicobacter pylori is a leading cause of peptic ulcer disease and has been identified as an important risk factor for gastric cancer. Current recommended treatments for H. pylori infection generally involve a combination of antibiotics together with an acid suppressant, such as a proton-pump inhibitor (PPI). However, treatment success rates with current guideline-recommended PPI-based regimens remain suboptimal. Vonoprazan (Voquezna^®), from a new class of drugs known as potassium-competitive acid blockers, has the potential to provide potent and sustained acid suppression. Based on the findings of a pivotal trial (PHALCON-HP) conducted in the USA and Europe, vonoprazan is now approved in the USA for the treatment of H. pylori infection in adults when used in combination with amoxicillin, or amoxicillin and clarithromycin. Alongside the demonstrated efficacy and tolerability of the vonoprazan-based regimens, vonoprazan has a rapid onset of action and can be taken with or without food. Thus, vonoprazan-based dual and triple therapy regimens present valuable alternatives to standard PPI-based triple therapy in the treatment of H. pylori infection.

Etrasimod: First Approval.

Etrasimod (VELSIPITY™) is an orally available, small-molecule selective sphingosine-1-phosphate (S1P) receptor modulator being developed by Pfizer for the treatment of ulcerative colitis and other immune-mediated inflammatory disorders. Etrasimod is selective for S1P receptor subtypes S1P1, S1P4 and S1P5 while having minimal activity on S1P3 and no activity on S1P2. Etrasimod received its first approval, in the USA, in October 2023 for the treatment of moderately to severely active ulcerative colitis in adults. Subsequently, the European Medicines Agency adopted a positive opinion in December 2023, recommending the granting of marketing authorisation for etrasimod for the treatment of patients aged ≥ 16 years with moderately to severely active ulcerative colitis who have had an inadequate response, lost response, or were intolerant to either conventional therapy, or a biological agent. Etrasimod is also under regulatory review for the treatment of ulcerative colitis in several other countries. Clinical development of etrasimod for use in the treatment of Crohn's disease, atopic dermatitis, eosinophilic oesophagitis and alopecia areata is ongoing worldwide. This article summarises the milestones in the development of etrasimod leading to this first approval for the treatment of ulcerative colitis in adults.

Capivasertib: First Approval.

Capivasertib (Truqap™) is an orally available, small-molecule pan-AKT inhibitor being developed by AstraZeneca for the treatment of various cancers, including breast and prostate cancers. Capivasertib received its first approval, in the USA, in November 2023 for use in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy. Capivasertib is also under regulatory review for HR-positive, HER2-negative breast cancer in the EU and several other countries, and in phase III clinical development for use (in combination with other anti-cancer agents) in the treatment of triple-negative breast cancer, castration-resistant prostate cancer, and hormone-sensitive prostate cancer. This article summarizes the milestones in the development of capivasertib leading to this first approval for HR-positive, HER2-negative, locally advanced or metastatic breast cancer.

Zilucoplan: First Approval.

Zilucoplan (Zilbrysq®) is a subcutaneously administered macrocyclic peptide inhibitor of complement component 5 (C5 inhibitor) being developed by UCB for the treatment of generalised myasthenia gravis (gMG). Zilucoplan received its first approval, in Japan, in September 2023 for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants and are positive for anti-acetylcholine receptor (AChR) antibodies. Subsequently, zilucoplan was approved in the USA in October 2023 for the treatment of gMG in adult patients who are anti-AChR antibody positive and in the EU in December 2023 as an add-on to standard therapy for the treatment of gMG in adult patients who are anti-AChR antibody positive. Zilucoplan is also currently under regulatory review in Australia and Canada for use in the treatment of gMG. This article summarises the milestones in the development of zilucoplan leading to this first approval for gMG.

Mitapivat: A Review in Pyruvate Kinase Deficiency in Adults.

Mitapivat (Pyrukynd®), an oral, allosteric activator of pyruvate kinase (PK), is approved in the USA for the treatment of haemolytic anaemia in adults with PK deficiency and in the EU and UK for the treatment of PK deficiency in adults. Mitapivat acts by restoring activity of the red blood cell (RBC) PK enzyme, which is dysfunctional due to genetic mutations in the PKLR gene in patients with PK deficiency. In the double-blind placebo-controlled phase III ACTIVATE trial in adults with PK deficiency who were not regularly RBC transfused, mitapivat was superior to placebo in improving haemoglobin levels. In the single-arm phase III ACTIVATE-T trial in adults with PK deficiency who were regularly RBC transfused, a reduction in RBC transfusion burden was observed with mitapivat. In both trials, mitapivat improved other clinical parameters of haemolysis and patient-reported health-related quality of life. At the approved twice-daily dosage range, mitapivat was generally well tolerated, with adverse events generally being mild to moderate in severity. Results from an ongoing extension study in previously enrolled phase III trial patients will be of interest. Currently available data indicate that mitapivat, the first approved disease-modifying drug for PK deficiency in adults, is a valuable treatment option for this rare disease.

Pyruvate kinase (PK) deficiency is a rare hereditary disease caused by mutations affecting the function of the PK enzyme in red blood cells (RBCs) and is characterized by chronic haemolytic anaemia. Treatment options for adults with PK deficiency have historically been limited to supportive care and are themselves associated with potentially serious complications. Oral mitapivat (Pyrukynd^®) is the first disease-modifying drug to be approved for use in adults with PK deficiency and acts by restoring activity of the dysfunctional RBC PK enzyme. Based on findings from two phase III clinical trials, twice-daily oral mitapivat provided clinical benefit in adults with PK deficiency, both in patients not requiring, and requiring, regular RBC transfusions. Improvements in disease-specific health-related quality of life were observed in adults with PK deficiency treated with mitapivat. Mitapivat was generally well tolerated, with most adverse events being mild to moderate in severity. In conclusion, current evidence indicates that mitapivat is a valuable treatment option for adults with PK deficiency.

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis.

Silencing the transthyretin (TTR) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra®), an RNA interference (RNAi) therapeutic targeting TTR mRNA, is approved in the USA and EU for the treatment of adults with polyneuropathy of hATTR amyloidosis. N-acetylgalactosamine conjugation and enhanced stabilisation chemistry are utilised to target vutrisiran to the liver and increase stability, respectively, allowing for subcutaneous administration once every 3 months. In a pivotal phase 3 study in patients with hATTR amyloidosis with polyneuropathy, subcutaneous vutrisiran 25 mg every 3 months significantly reduced neuropathy impairment versus external placebo. Vutrisiran was also associated with significant improvements in neuropathy-specific quality of life, gait speed, nutritional status and disability scores. Vutrisiran was generally well tolerated; the only common adverse events to occur at a greater incidence than with external placebo were pain in extremity and arthralgia. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is recommended. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, which has the potential advantage of infrequent subcutaneous dosage.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive and disabling disease caused by variants in the transthyretin (TTR) gene, which cause destabilisation and misfolding of the TTR protein. Deposition of misfolded TTR protein (amyloid) around nerves causes a range of neuropathic symptoms. Vutrisiran (Amvuttra^®) silences the TTR gene via RNA interference (RNAi). Vutrisiran, administered subcutaneously once every 3 months, is approved in the USA and EU for the treatment of polyneuropathy of hATTR amyloidosis in adults. In a phase 3 study in patients with hATTR amyloidosis with polyneuropathy, vutrisiran significantly reduced neuropathy impairment and improved other disease-related outcomes versus external placebo. Vutrisiran was generally well tolerated, with most adverse events being mild or moderate in severity. As vutrisiran decreases vitamin A levels, patients undergoing vutrisiran treatment should supplement with vitamin A. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, with a convenient dosage regimen.

20­Valent Pneumococcal Conjugate Vaccine: Pediatric First Approval.

20­valent pneumococcal conjugate vaccine (PCV20; Prevnar 20®; Apexxnar®) is a pneumococcal conjugate vaccine (PCV) developed by Pfizer for active immunization for the prevention of pneumococcal infections. PCV20 has a similar structure and formulation to Pfizer's 13-valent PCV (PCV13; Prevnar 13®; Prevenar 13®), with the addition of polysaccharides to target seven further Streptococcus pneumoniae serotypes (8, 10A, 11A, 12F, 15B, 22F and 33F). PCV20 has been approved for active immunization for the prevention of pneumonia and invasive disease caused by S. pneumoniae in adults since June 2021 in the USA and since February 2022 in the EU. Following further evaluation of its safety, immunogenicity, and effectiveness in pediatric populations, in April 2023 PCV20 received its first pediatric approval, in the USA, for active immunization for the prevention of invasive pneumococcal disease (IPD) caused by S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 6 weeks to 17 years of age and for the prevention of otitis media caused by S. pneumoniae serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F in individuals 6 weeks to 5 years of age. This article summarizes the milestones in the development of PCV20 leading to this first pediatric approval for active immunization for the prevention of IPD and otitis media caused by S. pneumoniae.

Glofitamab: First Approval.

Glofitamab (Columvi®) is a CD20 × CD3 T-cell-engaging bispecific monoclonal antibody being developed by Roche for the treatment of B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma (DLBCL). Glofitamab received its first approval (with conditions) on 25 March 2023, in Canada, for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, DLBCL arising from follicular lymphoma, or primary mediastinal B-cell lymphoma, who have received two or more lines of systemic therapy and are ineligible to receive or cannot receive CAR T-cell therapy or have previously received CAR T-cell therapy. Glofitamab is also under regulatory review for relapsed or refractory DLBCL in the EU and USA and in April 2023 received a positive opinion recommending the granting of a conditional marketing authorization in the EU. Clinical development of glofitamab, as a monotherapy and in combination with other agents for the treatment of non-Hodgkin lymphomas, is continuing worldwide. This article summarizes the milestones in the development of glofitamab leading to this first approval for relapsed or refractory DLBCL.

Baricitinib: A Review in Severe Alopecia Areata.

Baricitinib (Olumiant®), a Janus kinase (JAK) inhibitor, is the first drug approved for the treatment of severe alopecia areata in the USA and the EU. Severe alopecia areata is usually difficult to treat and relapse is common. Patients with this disorder are more likely to suffer from anxiety and depression. In two pivotal placebo-controlled phase 3 clinical trials in adults with severe alopecia areata, oral baricitinib once daily was associated with clinically meaningful scalp, eyebrow, and eyelash hair regrowth over 36 weeks. Baricitinib was generally well tolerated with the most common adverse events being infections, headaches, acne, and elevated levels of creatine phosphokinase. While longer-term data will be necessary to more fully understand the benefits and risks of the drug, currently available data suggest that baricitinib is a useful treatment for patients with severe alopecia areata.

Alopecia areata is a disorder in which an autoimmune attack is mounted against hair follicles, resulting in hair loss ranging from patches of hair loss through to complete hair loss. Alopecia areata can recur throughout an individual's lifetime and can cause significant psychological distress, with patients more likely to experience anxiety or depressive disorders within their lifetime. Baricitinib (Olumiant^®) is a drug that blocks the signaling of immune messengers to halt autoimmune attack and allow hair regrowth. In two clinical trials, adults with severe alopecia areata receiving baricitinib were more likely to recover from an episode of alopecia areata (achieve 80% or more scalp coverage) than those receiving placebo. Eyebrow and eyelash regrowth was also more common in patients receiving baricitinib than placebo. Baricitinib was generally well tolerated, with infections being the most common adverse events. While longer-term data will be of interest, baricitinib appears to be a useful treatment for patients with severe alopecia areata.

Satralizumab: A Review in Neuromyelitis Optica Spectrum Disorder.

Satralizumab (Enspryng®) is a monoclonal antibody that blocks the interleukin-6 (IL-6) receptor and is approved for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in patients who are aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive. Patients with NMOSD are at risk of recurrent autoimmune attacks that primarily target the optic nerves and spinal cord but may also target other regions of the central nervous system; these attacks can lead to life-long disability. In the randomized, placebo-controlled phase III SAkuraSky and SAkuraStar trials, subcutaneous satralizumab as an add-on to immunosuppressive therapy or as a monotherapy, respectively, significantly reduced the risk of relapse compared with placebo in patients who were AQP4-IgG seropositive with NMOSD. Satralizumab was well tolerated; the most common adverse events were infection, headache, arthralgia, decreased white blood cell count, hyperlipidaemia and injection-related reactions. In the EU, satralizumab is the first IL-6 receptor blocker to be approved for treatment of AQP4-IgG-seropositive patients with NMOSD, has the potential advantage of subcutaneous administration, and is the only targeted treatment approved for adolescent patients with this disorder. Thus, satralizumab is a valuable treatment option for patients with NMOSD.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder, in which recurrent attacks by the body's own immune system can cause severe morbidity and disability. Immunoglobulin G antibodies targeting the aquaporin-4 (AQP4-IgG) water channel in cells of the central nervous system can be detected in the majority of patients with NMOSD. Satralizumab (Enspryng^®), which is designed to suppress autoantibody production by blocking the interleukin-6 (IL-6) receptor, was found to significantly reduce the rate of immune attack recurrence compared with placebo when used as an add-on to standard immunosuppressive therapy (SAkuraSky trial) or when used alone (SAkuraStar trial). Satralizumab was well tolerated in the SAkuraSky and SAkuraStar trials, with infections (e.g. nasopharyngitis, upper respiratory tract infections) being the most common associated adverse event. In the EU, satralizumab is the first IL-6 receptor blocker approved for AQP4-IgG-seropositive patients with NMOSD and is the only subcutaneously administration targeted drug approved for NMOSD. Therefore, satralizumab represents a valuable treatment option for NMOSD.

Relugolix: A Review in Advanced Prostate Cancer.

Relugolix (Orgovyx®), an orally active nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist that provides rapid testosterone suppression, is indicated in the USA for the treatment of advanced prostate cancer and in the EU for advanced hormone-sensitive prostate cancer. In the pivotal phase III HERO trial in men with advanced prostate cancer, once-daily oral relugolix (with a loading dose on day 1) led to a sustained castration rate over 48 weeks of treatment of > 90%, a rate that was non-inferior to that provided by intramuscular leuprolide depot every 3 months (with an exploratory analysis further indicating the superiority of relugolix over leuprolide). Relugolix was generally well tolerated, having an adverse event profile that is consistent with testosterone suppression. Furthermore, there is evidence that relugolix may be associated with a lower risk of major adverse cardiac events compared with leuprolide. With the ability to provide the rapid testosterone suppression (with no initial surge in testosterone upon treatment initiation) combined with the benefits of oral administration and potentially improved cardiac safety, relugolix presents a valuable treatment option for men with advanced prostate cancer where androgen deprivation therapy is indicated.

Androgen deprivation therapy (ADT), a key component of prostate cancer treatment, reduces testosterone production to slow disease progression. Relugolix (Orgovyx^®), from a class of drugs known as gonadotropin-releasing hormone (GnRH) receptor antagonists, is approved for the treatment of advanced prostate cancer. Whereas some ADT agents (i.e. GnRH agonists) produce an initial surge in testosterone levels (with the potential to cause a flare in disease symptoms), GnRH receptor antagonists, of which relugolix is the first available as an oral medication, provide rapid testosterone suppression with no initial surge. In a key clinical trial in men with advanced prostate cancer, once-daily relugolix provided sustained castration in > 90% of patients, with a sustained castration rate that was non-inferior to that of a comparator agent (leuprolide) administered by intramuscular injection every 3 months. Relugolix was generally well tolerated and may be associated with a lower risk of major adverse cardiac events than leuprolide. Providing rapid and sustained testosterone suppression, combined with the benefits of oral administration and potentially improved cardiac safety, relugolix presents a valuable treatment option for ADT in men with advanced prostate cancer.

Ripretinib: A Review in Gastrointestinal Stromal Tumours as Fourth-or Later-Line of Therapy.

Ripretinib (Qinlock®) is a small molecule inhibitor of the receptor tyrosine kinases KIT and platelet-derived growth factor receptor α (PDGFRA) and is approved for the treatment of gastrointestinal stromal tumours as a fourth-line of therapy. After successive cycles of treatment, gastrointestinal stromal tumours can carry a wide array of mutations, which makes resistance to treatment more likely. Ripretinib has a dual mechanism of action that allows it to target a broad spectrum of mutations in KIT or PDGFRA. The pivotal phase III INVICTUS trial demonstrated an increase of progression-free survival in patients receiving ripretinib compared with placebo, with efficacy being maintained across patients with KIT exon 9, 11, 13 and 17 mutations. Ripretinib has acceptable tolerability, with the most common drug-related grade 3 or 4 adverse events being lipase increases, hypertension, fatigue and hypophosphataemia. Ripretinib is therefore a valuable additional line of therapy available for the management of gastrointestinal stromal tumours.

The receptor tyrosine kinases KIT and platelet-derived growth factor receptor α (PDGFRA) regulate cell growth and survival; mutations in the genes of these proteins are the most common causes of gastrointestinal stromal tumours. Drugs that target kinases are a mainstay in the treatment of these cancers; however, new mutations often occur that make tumours resistant to kinase inhibitors. Ripretinib (Qinlock^®) is approved for patients with gastrointestinal stromal tumours after the tumour has become resistant to three or more other kinase inhibitors. In a pivotal phase III clinical trial in patients with gastrointestinal stromal tumours and who had failure with three or more prior treatments, ripretinib significantly delayed disease progression compared with placebo. Ripretinib has an acceptable side effect profile, with the most common drug-related side effects being alopecia, muscle pain and nausea. Thus, ripretinib is a valuable treatment option in the management of advanced gastrointestinal stromal tumours.

20-Valent Pneumococcal Conjugate Vaccine: A Review of Its Use in Adults.

The introduction of multi-valent pneumococcal vaccines around the world, such as the 13-valent pneumococcal conjugate vaccine (PCV13), has had a significant effect in reducing the burden of disease caused by Streptococcus pneumoniae infection globally. However, S. pneumoniae serotypes not covered by PCV13 still cause significant disease. A 20-valent pneumococcal conjugate vaccine (PCV20; Prevnar20®; Apexxnar®) has recently been licensed for active immunisation for the prevention of invasive disease and pneumonia caused by S. pneumoniae in adults. PCV20 contains all components of PCV13 with the addition of polysaccharide conjugates of seven more serotypes, selected based on their generalised geographic distribution and relative prevalence as a cause of pneumococcal disease. The immunogenicity of PCV20 in adults has been demonstrated in a well-designed program of clinical trials which showed that PCV20 administered as a single dose by intramuscular injection induced robust immune responses to all 20 S. pneumoniae serotypes covered by the vaccine. PCV20 was well tolerated, with a tolerability and safety profile similar to that for PCV13. By expanding the coverage of disease-causing S. pneumoniae serotypes relative to other PCVs, PCV20 presents a valuable new tool with the potential to further reduce the impact of pneumococcal disease.

Pneumonia and other diseases caused by infection with the bacterium Streptococcus pneumoniae are a significant health concern. The introduction of vaccines targeting multiple S. pneumoniae serotypes [such as the 13-valent pneumococcal conjugate vaccine (PCV13)] has had a significant effect in reducing pneumococcal disease; however, serotypes not covered by PCV13 still cause significant disease. Recently, a new vaccine [20-valent pneumococcal conjugate vaccine (PCV20; Prevnar20^®; Apexxnar^®)] has been developed and licensed for use in immunisation for the prevention of invasive disease and pneumonia caused by S. pneumoniae in adults. The ability of PCV20 (administered as a single dose by intramuscular injection) to elicit strong immune responses to all 20 serotypes covered by the vaccine was demonstrated in a well-designed program of clinical trials. PCV20 is well tolerated, with pain at the injection site and muscle pain being the most common adverse reactions. By expanding the coverage of disease-causing S. pneumoniae serotypes, PCV20 presents a valuable new tool with the potential to further reduce the impact of pneumococcal disease.

Delafloxacin: A Review in Community-Acquired Pneumonia.

Delafloxacin (BAXDELA® in the USA; Quofenix® in the EU) is an anionic fluoroquinolone antibacterial that is approved for the treatment of community-acquired pneumonia (CAP) and acute bacterial skin and skin structure infections in adults. Delafloxacin demonstrated in vitro activity against Gram-positive and Gram-negative pathogens, including drug-resistant isolates. In a phase III trial in adults with CAP, delafloxacin was noninferior to moxifloxacin when assessed against FDA- and EMA-defined primary endpoints, with both fluoroquinolones achieving high treatment success rates. A prespecified subgroup analysis suggested that delafloxacin may be more efficacious than moxifloxacin in patients with a history of asthma or chronic obstructive pulmonary disease (COPD). Delafloxacin was generally well tolerated in patients with CAP, with most treatment-emergent adverse events graded as mild or moderate in severity. Fluoroquinolone-associated adverse events of special interest occurred infrequently, with no events of QT prolongation or phototoxicity reported with delafloxacin. Delafloxacin is an effective and generally well-tolerated treatment that increases the number of available treatments for CAP and, although further research is required, may be a useful option for patients with CAP and comorbid asthma or COPD.

Community-acquired pneumonia (CAP) can be caused by bacterial infection of the lungs, and is a common cause of infection-related deaths. As drug-resistant bacteria are becoming more common, new antibacterial drugs are needed. Delafloxacin (BAXDELA^® in the USA; Quofenix^® in the EU) is a fluoroquinolone antibacterial that inhibits bacterial enzymes required for DNA repair and replication. Delafloxacin kills a wide range of bacteria, including some drug-resistant variants. During a trial in adults with CAP, delafloxacin was as effective as moxifloxacin (also a fluoroquinolone antibacterial). Delafloxacin may be more effective than moxifloxacin in patients with a history of asthma or chronic obstructive pulmonary disease (COPD), although further research is needed. Most adverse events with delafloxacin were mild or moderate in severity, with diarrhoea being the most commonly occurring treatment-related adverse event (experienced by < 4% of recipients). Furthermore, the adverse effects of delafloxacin were generally consistent with those previously observed in patients with skin infections. Delafloxacin expands the range of treatments for CAP, and is potentially useful for patients with comorbid asthma or COPD.

Faricimab: First Approval.

Faricimab (faricimab-svoa; Vabysmo™) is a bispecific antibody that binds to and inhibits both vascular endothelial growth factor (VEGF)-A and angiopoietin-2 (Ang-2). Administered by intravitreal injection, faricimab is being developed by Roche/Genentech for use in the treatment of retinal vascular diseases. In January 2022 faricimab received its first approvals, in the USA, for use in the treatment of patients with neovascular (wet) age-related macular degeneration (nAMD) or diabetic macular edema (DME). Faricimab has also recently been approved in Japan, and is currently under regulatory review in the EU, for use in nAMD and DME. Phase III clinical development of faricimab for use in the treatment of nAMD, DME, and macular edema due to retinal vein occlusion is continuing in multiple other countries worldwide. This article summarizes the milestones in the development of faricimab leading to these first approvals for nAMD and DME in the USA.