Bayer (New Zealand)

) is approved in the USA for the management of osteoarthritis (OA) pain of the knee and is administered as a single, 5 mL intra-articular (IA) injection. Although the therapeutic effects from IA corticosteroids are typically short-lived, triamcinolone acetonide ER is formulated in poly (lactic-co-glycolic acid) (PLGA) microspheres that slowly release triamcinolone acetonide in the synovium, enabling their prolonged presence in the joint. This reduces systemic exposure and lessens corticosteroid-related systemic adverse reactions, such as blood glucose elevations. In a 24-week, randomized, phase III clinical trial, triamcinolone acetonide ER 32 mg significantly improved mean average daily pain intensity in patients with knee OA relative to placebo, and pain, stiffness and physical function (according to WOMAC criteria) relative to placebo and triamcinolone acetonide crystalline suspension (CS). Triamcinolone acetonide ER was generally well tolerated, with a tolerability profile similar to that of triamcinolone acetonide CS and placebo. Findings from a single-arm phase IIIb study indicated that a repeat administration of triamcinolone acetonide ER may be similarly efficacious to an initial injection without having deleterious effects on cartilage or other aspects of joint structure. Thus, triamcinolone acetonide ER expands the treatment options available for the management of OA pain of the knee.

Eravacycline (Xerava™), a novel fully synthetic fluorocycline, consists of the tetracyclic core scaffold with unique modifications in the tetracyclic D ring; consequently, it exhibits potent in vitro activity against Gram-positive and -negative bacterial strains expressing certain common tetracycline-specific acquired resistance mechanisms. In vitro, eravacycline exhibits potent activity against a broad spectrum of clinically relevant Gram-positive and -negative aerobic and anaerobic bacteria. Intravenous eravacycline is approved in several countries for the treatment of complicated intra-abdominal infections (cIAIs) in adult patients. In two pivotal double-blind, multinational trials in this patient population, eravacycline (infusion ≈ 1 h) was noninferior to intravenous ertapenem or meropenem at the test-of-cure visit in terms of clinical response rates in all prespecified populations. Eravacycline had an acceptable tolerability profile, with infusion site reactions, nausea, vomiting and diarrhoea the most commonly reported adverse reactions, most of which were of mild to moderate severity. Given its broad spectrum of activity against common clinically relevant pathogens (including those expressing certain tetracycline- and other antibacterial-specific acquired resistance mechanisms) and its more potent in vitro activity and better tolerability profile than tigecycline, eravacycline provides a novel emerging option for the treatment of adult patients with cIAIs, especially as empirical therapy when coverage of resistant pathogens is required.

Elagolix (ORILISSA™), an orally bioavailable, second-generation, non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist, is being developed AbbVie and Neurocrine Biosciences for the treatment of reproductive hormone-dependent disorders in women. In July 2018, the US FDA approved elagolix tablets for the management of moderate to severe pain associated with endometriosis. This approval was based on positive results in two replicate phase III trials; additional phase III trials in the USA, Canada and Puerto Rico are currently evaluating elagolix as both monotherapy and in combination with low-dose hormone add-back therapy in the same indication. Elagolix with and without low-dose hormone add-back therapy is also undergoing phase III clinical development for heavy menstrual bleeding associated with uterine fibroids in the aforementioned locations. This article summarizes the milestones in the development of elagolix leading to its first approval for the management of moderate to severe pain associated with endometriosis.

), an orally administered kinase inhibitor, is being developed by Pfizer for the treatment of alopecia areata, vitiligo, ulcerative colitis and Crohn's disease. On 23 June 2023, ritlecitinib received approval in the USA for the treatment of severe alopecia areata in adults and adolescents 12 years and older. Ritlecitinib was approved in Japan on 26 June 2023 for the treatment of alopecia areata (limited to intractable cases involving widespread hair loss). Ritlecitinib has also received a positive opinion in the EU and is under regulatory review in the UK and China. This article summarizes the milestones in the development of ritlecitinib leading to this first approval for severe alopecia areata.

) is a long-acting capsid inhibitor of human immunodeficiency virus type 1 (HIV-1) being developed by Gilead Sciences Inc. It is available as an oral tablet and injectable solution, with the latter being a slow-release formulation to allow bi-annual subcutaneous administration. In August 2022, lenacapavir received its first approval in the EU for use in combination with other antiretroviral(s) in adults with multi-drug resistant HIV infection, for whom it is otherwise not possible to construct a suppressive anti-viral regimen. This article summarizes the milestones in the development of lenacapavir leading to this first approval for the treatment of HIV-1 infection.

The human-animal bond has been a fundamental feature of mankind's history for millennia. The first, and strongest of these, man's relationship with the dog, is believed to pre-date even agriculture, going back as far as 30,000 years. It remains at least as powerful today. Fed by the changing nature of the interactions between people and their dogs worldwide and the increasing tendency towards close domesticity, the health of dogs has never played a more important role in family life. Thanks to developments in scientific understanding and diagnostic techniques, as well as changing priorities of pet owners, veterinarians are now able, and indeed expected, to play a fundamental role in the prevention and treatment of canine disease, including canine vector-borne diseases (CVBDs).The CVBDs represent a varied and complex group of diseases, including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, leishmaniosis, rickettsiosis and thelaziosis, with new syndromes being uncovered every year. Many of these diseases can cause serious, even life-threatening clinical conditions in dogs, with a number having zoonotic potential, affecting the human population.Today, CVBDs pose a growing global threat as they continue their spread far from their traditional geographical and temporal restraints as a result of changes in both climatic conditions and pet dog travel patterns, exposing new populations to previously unknown infectious agents and posing unprecedented challenges to veterinarians.In response to this growing threat, the CVBD World Forum, a multidisciplinary group of experts in CVBDs from around the world which meets on an annual basis, gathered in Nice (France) in 2011 to share the latest research on CVBDs and discuss the best approaches to managing these diseases around the world.As a result of these discussions, we, the members of the CVBD Forum have developed the following recommendations to veterinarians for the management of CVBDs.

Ripretinib (QINLOCK™) is a novel type II tyrosine switch control inhibitor being developed by Deciphera Pharmaceuticals for the treatment of KIT proto-oncogene receptor tyrosine kinase (KIT)-driven and/or platelet derived growth factor receptor A (PDGFRA)-driven cancers, including gastrointestinal stromal tumour (GIST). Ripretinib inhibits KIT and PDGFRA kinase, including wild-type, primary and secondary mutations, as well as other kinases, such as PDGFRB, TIE2, VEGFR2 and BRAF. In May 2020, oral ripretinib received its first approval in the USA for the treatment of adult patients with advanced GIST who have received prior treatment with ≥ 3 kinase inhibitors, including imatinib. The US FDA, Health Canada and the Australian Therapeutic Goods Administration collaborated on the review of the ripretinib new drug application in this indication as part of Project Orbis; regulatory review in Australia and Canada is ongoing. Clinical development for GIST, solid tumours and systemic mastocytosis is underway in several countries worldwide. This article summarizes the milestones in the development of ripretinib leading to this first approval for the treatment of advanced GIST.

) is a non-replicating adenoviral vector-based gene therapy developed by Ferring Pharmaceuticals for the treatment of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). Nadofaragene firadenovec constitutes vector DNA that encodes for interferon (IFN)-α2b and is the first approved gene therapy in bladder cancer. The production of IFN-α2b by transfected urothelial cells is associated with anticancer activity, including immunostimulatory, antiangiogenic and apoptotic effects. In December 2022, nadofaragene firadenovec received its first global approval in the USA for the treatment of high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumours in adults. This article summarizes the milestones in the development of nadofaragene firadenovec leading to this first approval for this indication.

Cladribine is a deoxyadenosine analogue prodrug that preferentially depletes lymphocytes, key cells underlying multiple sclerosis (MS) pathogenesis. Cladribine tablets (Mavenclad®) represent the first short-course oral disease-modifying drug (DMD) for use in MS. The tablets, administered in two short courses 1 year apart, are indicated for the treatment of adults with highly active relapsing MS on the basis of data from pivotal clinical trials, including the phase 3 study CLARITY and its extension. A cumulative cladribine tablets dose of 3.5 mg/kg administered in this fashion in CLARITY reduced clinical relapse, disability progression and MRI-assessed disease activity and also improved some aspects of health-related quality of life (HR-QOL) versus placebo over 96 weeks in adults with relapsing-remitting MS (RRMS). Moreover, in the 96-week extension (plus 24 weeks’ supplemental follow-up), no additional clinical benefit was gained from continuing versus discontinuing cladribine tablets after the first two annual courses of therapy, although MRI activity was more notable in a subset of cladribine tablet recipients who discontinued the drug. In post hoc analyses of CLARITY and/or a phase 2b trial, benefits of cladribine tablets were seen in patients with high disease activity (HDA) relapsing MS that were sometimes greater than in patients without HDA. Cladribine tablets have an acceptable tolerability profile and do not appear to be associated with an increased risk of overall infection or with an increased risk of malignancy (vs. matched reference populations). Active comparisons and longer-term follow-up would be beneficial, although current data indicate that for adults with highly active relapsing MS, cladribine tablets are an effective treatment option with the convenience of low-burden, short-course, oral administration.

(USA)] is a second-generation, extracellular non-ionic macrocyclic gadolinium-based contrast agent (GBCA) that is approved for use in paediatric (including term neonates) and adult patients undergoing diagnostic contrast-enhanced (CE) MRI for visualization of pathological lesions in all body regions or for CE MRA to evaluate perfusion and flow-related abnormalities. Its unique physicochemical profile, including its high thermostability and proton relaxation times, means that gadobutrol is formulated at twice the gadolinium ion concentration of other GBCAs, resulting in a narrower bolus and consequently, improved dynamic image enhancement. Based on > 20 years of experience in the clinical trial and real-world settings (> 50 million doses) and its low risk for developing nephrogenic systemic fibrosis (NSF), gadobutrol represents an effective and safe diagnostic GBCA for use in CE MRI and MRA to visualize pathological lesions and vascular perfusion and flow-related abnormalities in all body regions in a broad spectrum of patients, including term neonates and other paediatric patients, young and elderly adult patients, and those with moderate or severe renal or hepatic impairment or cardiovascular (CV) disease.

Abstract Efforts to eradicate multiple mammal pests from offshore islands and fenced mainland ‘habitat islands’ often fail to remove mice, and such failures can result in a dramatic change in the food‐web whereby the removal of larger mammal pests facilitates a population explosion of mice through predator and competitor release. We investigated the ecological responses of house mice to the removal of mammalian predators from a 500‐ha fenced sanctuary at Tawharanui, northern New Zealand. Data on population structure and body condition of mice trapped in 2007, in four habitat types within the sanctuary, were compared with baseline data collected in 2001, before mammal control operations commenced. We hypothesized that: (i) in the absence of mammalian predators mouse densities would increase in all habitat types that provide vegetation cover, and (ii) in the absence of mammalian competitors mice would become heavier due to greater access to food resources. Mouse densities were significantly higher in 2007 than in 2001 in three habitat types. The high density of mice in forest – where none were trapped prior to control – suggests a competitive release, in which mice profited from the removal of ship rats. No mice were caught in the presence of ship rats on a forest trap‐line at a control site outside the sanctuary. Mice trapped in 2007 were significantly heavier than those trapped in 2001, and significantly heavier than mice trapped at the control site. Greater access to food in the absence of competing and predatory mammals probably explains the heavier body weight of Tawharanui mice. There has been a significant change in the mammalian food‐web at Tawharanui, such that the house mouse is now the primary pest. A rapid and dramatic increase in mouse numbers is likely to adversely impact invertebrates and seedling recruitment, which in turn could affect ecosystem functions.

One of the problems in planning cutaneous surgery is that human skin is anisotropic, or directionally dependent. Indeed, skin tension varies between individuals and at different body sites. Many a surgeon has tried to design different devices to measure skin tension to help plan excisional surgery, or to understand wound healing. However, many of the devices have been beset with problems due to many confounding variables - differences in technical ability, material (sutures) used and variability between different users. We describe the development of a new skin tensiometer that overcomes many historical technical issues. A new skin tension measuring device is presented here. It was designed to be less user-dependent, more reliable and usable on different bodily sites. The design and computational optimizations are discussed. Our skin tensiometer has helped understand the differences between incisional and excisional skin lines. Langer, who pioneered the concept of skin tension lines, created incisional lines that differ from lines caused by forces that need to be overcome when large wounds are closed surgically (excisional tension). The use of this innovative device has led to understanding of skin biomechanics and best excisional skin tension (BEST) lines.

Sparsentan (FILSPARI™) is an oral, dual endothelin angiotensin receptor antagonist that is being developed by Travere Therapeutics for the treatment of immunoglobulin A (IgA) nephropathy and focal segmental glomerulosclerosis (FSGS). In February 2023, sparsentan received accelerated approval in the USA for reducing proteinuria in adults with primary IgA nephropathy who are at risk of rapid disease progression. This article summarizes the milestones in the development of sparsentan leading to this first approval for IgA nephropathy.

Eplontersen (Wainua™) is a ligand-conjugated antisense oligonucleotide directed to TTR, which is being developed by Ionis Pharmaceuticals and AstraZeneca for the treatment of TTR-mediated amyloidosis (ATTR). Eplontersen, which is targeted to the liver by a ligand containing three N-acetyl galactosamine residues, binds to wild-type and variant TTR mRNA, thus reducing the levels of circulating TTR protein and amyloid deposition. Subcutaneous eplontersen reduced serum TTR levels, inhibited neuropathy progression and improved health-related quality of life in patients with polyneuropathy of hereditary ATTR (ATTRv-PN; v for variant) in a phase III trial. Based on these results, eplontersen was approved in the USA for the treatment of ATTRv-PN on 21 December 2023 and is currently undergoing regulatory review for a similar indication in the EU, the UK, Switzerland and Canada. Eplontersen is also undergoing phase III development for ATTR cardiomyopathy. This article summarizes the milestones in the development of eplontersen leading to this first approval for ATTRv-PN.

The human race has been exposed to the potential toxicity of hydrocarbons, whether by the inhaled or ingested route, for thousands of years and the consequent inflammatory reaction in the lungs depends on the degree of exposure, volatility and viscosity of the particular hydrocarbon in question. Heating, lighting, transportation, industry and nature all provide the potential for both inhalation and/or ingestion of hydrocarbons. Some forms, such as those related to petroleum products, e.g. diesel exhaust particles (DEP) and polycyclic aromatic hydrocarbons (PAH) have been shown to cause both malignant and non-malignant respiratory diseases. Accidental ingestion represents another significant exposure risk and we now have increasing evidence that pollutant particles may adsorb allergens to their surface and potentially enhance the allergic response. It seems unlikely that this potential will significantly decrease in the near future and depending on individual socio-economic circumstances, work environment and habitation, the risks of significant lung disease will vary. This review outlines the domestic, outdoor, occupational and natural sources of hydrocarbon exposure and considers the evidence relating to radiological and pathological lung changes in both animals and man. The acute effects of hydrocarbon toxicity are well recognised but the effects of longer term, lower exposure, and the mechanisms of their toxicity, require further research.

) is a high affinity humanized immunoglobulin G4 monoclonal antibody directed against human neonatal Fc receptor (FcRn). Administered subcutaneously, it is being developed by UCB Pharma for the treatment of autoimmune diseases and received its first approval on 27 June 2023 in the USA for the treatment of generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibody positive. Rozanolixizumab is the first agent to be approved in the USA for both anti-AChR and anti-MuSK antibody-positive gMG. A regulatory assessment of rozanolixizumab for the treatment of gMG is currently underway in the EU and Japan. Clinical development is ongoing for the treatment of leucine-rich glioma-inactivated 1 autoimmune encephalitis, myelin oligodendrocyte glycoprotein (MOG) antibody disease and severe fibromyalgia syndrome. This article summarizes the milestones in the development of rozanolixizumab leading to this first approval for the treatment of gMG in adults who are anti-AChR or anti-MuSK antibody positive.

Succinate dehydrogenase inhibitor (SDHI) fungicides are currently represented in New Zealand by eight active ingredients bixafen boscalid carboxin fluaxapyroxad fluopyram isopyrazam penthiopyrad and sedaxane They are either currently registered or undergoing development in New Zealand for use against a range of ascomycete and basiodiomycete pathogens in crops including cereals ryegrass seed apples pears grapes stonefruit cucurbits and kiwifruit These fungicides are considered to have medium to high risk of resistance development and resistance management is recommended by the Fungicide Resistance Action Committee (FRAC) in Europe Guidelines are presented for use of SDHI fungicides in New Zealand to help avoid or delay the development of resistance in the fungal pathogens that they target

; Servier) is an orally administered, first-in-class, highly brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes being developed for use in IDH-mutant diffuse glioma. Vorasidenib received its first approval on 6 August 2024, in the USA, for the treatment of adult and pediatric patients aged 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery, including biopsy, sub-total resection, or gross total resection. Approval was based on results from the multinational phase III INDIGO trial, in which vorasidenib significantly improved progression-free survival and time to the next anticancer intervention relative to placebo. In the EU and other countries worldwide, regulatory review of vorasidenib in IDH-mutant glioma is currently underway. This article summarizes the milestones in the development of vorasidenib leading to this first approval for glioma.

Surveillance for invading insect pests is costly and the trapper usually finds the traps empty of the target pest. Since the successful establishment of new pests is an uncommon event, multiple lures placed into one trap might increase the efficiency of the surveillance system. We investigated the effect of the combination of the Tephritidae male lures - trimedlure, cuelure, raspberry ketone and methyl eugenol - on catch of Ceratitis capitata, Zeugodacus cucurbitae, Bactrocera tryoni, B. dorsalis, B. aquilonis and B. tenuifascia in Australia and the USA (not all species are present in each country). The increase in trap density required to offset any reduction in catch due to the presence of lures for other Tephritidae was estimated. The effect of increasing trap density to maintain surveillance sensitivity was modelled for a hypothetical population of B. tryoni males, where the effective sampling area of cuelure traps for this species has been estimated. The 3-way combination significantly reduced the catch of the methyl eugenol-responsive B. dorsalis. Unexpectedly, we found that trimedlure-baited traps that contained methyl eugenol had ×3.1 lower catch of C. capitata than in trimedlure-only-baited traps in Australia, but not in Hawaii where no difference in catch was observed, we cannot satisfactorily explain this result. Based on the data presented here and from previous research, combinations of some male lures for the early detection of tephritid flies appear compatible and where there is any reduction in surveillance sensitivity observed, this can be offset by increasing the density of traps in the area.

Udder cleft dermatitis (UCD) is a well-known disorder in dairy cows. Veterinary literature about this subject, however, is scarce. The objectives of this study were to define a clinical scoring system for UCD, estimate the within-herd prevalence of UCD, and identify potential risk factors of UCD at cow and herd level. On 20 randomly selected dairy farms in the Netherlands, each lactating cow was photographed from a ventral, lateral, and caudal position. A scoring system with 6 categories of severity of UCD was proposed based on the ventral photographs. Cow measures such as udder width and depth, and front quarter attachment were determined from the lateral and caudal photographs. A questionnaire was conducted on each farm during farm visits. Udder cleft dermatitis, defined as a score 3 or higher, was detected in 5.2% of the 948 cows involved in this study. Within-herd prevalences of UCD ranged between 0 and 15% and UCD was found in 16 (80%) of the participating farms. Cows with a deep udder (relative to the hock), large front quarters, and a small angle between udder and abdominal wall were more likely to develop UCD. Production level and use of a footbath were identified as being positively associated with herd-level UCD prevalence. Herd size and average bulk milk somatic cell count did not seem to be associated with UCD prevalence. Because of the small herd sample size, no firm conclusions were drawn on herd-level risk factors. However, results from this study can be used in designing a future longitudinal UCD study. The prevalences of UCD found in the present study illustrate the current UCD situation in the Netherlands. Our results demonstrate that multiple potential risk factors of UCD could be identified at both the cow and herd level.