Patent Claim Scope and Biosimilar Competition in the US and EU.

The US has found it hard to establish competition in the market for biologics, which are therapeutics derived from living cells. In the case of small-molecule drugs, the emergence of direct competition from generic drugs at the end of the exclusivity period has provided the impetus for price competition, leading to lower spending. In 2010, to spur competition in the biologics market, Congress created a simplified pathway for the US Food and Drug Administration (FDA) to approve comparable versions of biologic drugs called biosimilars.

AI and biosecurity: The need for governance.

Governments should evaluate advanced models and if needed impose safety measures.

Comparing the Real-World and Clinical Trial Bleeding Rates Associated with Oral Anticoagulation Treatment for Atrial Fibrillation.

The prevention of stroke in patients with atrial fibrillation (AF) involves the use of oral anticoagulation, commonly in the form of direct oral anticoagulants (DOACs). However, it comes with an increased risk of bleeding, and therefore, counselling patients on their individual risks is important. Although the majority of patients initiated on DOACs have been represented within the clinical trials, some cohorts are under-represented in whom clinicians cannot practice evidence-based medicine.

One versus three weeks hypofractionated whole breast radiotherapy for early breast cancer treatment: the FAST-Forward phase III RCT.

Background: FAST-Forward aimed to identify a 5-fraction schedule of adjuvant radiotherapy delivered in 1 week that was non-inferior in terms of local cancer control and as safe as the standard 15-fraction regimen after primary surgery for early breast cancer. Published acute toxicity and 5-year results are presented here with other aspects of the trial.

Design: Multicentre phase III non-inferiority trial.

Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer (UK TACT2; CRUK/05/19): quality of life results from a multicentre, phase 3, open-label, randomised, controlled trial.

Background: Adjuvant chemotherapy for patients with early breast cancer improves outcomes but its toxicity affects patients' quality of life (QOL). The UK TACT2 trial investigated whether accelerated epirubicin improves time to recurrence and if oral capecitabine is non-inferior to cyclophosphamide, methotrexate, and fluorouracil (CMF) for efficacy with less toxicity. Results showed no benefit for accelerated epirubicin and capecitabine was non-inferior.

Patients' views and experiences on the supported self-management/patient-initiated follow up pathway for breast cancer.

Purpose: To explore patients' expectations and experience of Supportive Self-Management (SSM)/ Patient Initiated Follow Up (PIFU) following breast cancer treatments over a 12-month period.

Methods: In total, 32/110 (29%) patient participants in the PRAGMATIC (Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer) study were interviewed at baseline, 3, 6, 9 and 12 months. Interviews in this sub-study used a mix-methods approach to explore understanding of the pathway, confidence in self-management, triggers to seek help and/or re-engage with the clinical breast team and impact of the COVID-19 pandemic.

Patients' experiences of a suppoRted self-manAGeMent pAThway In breast Cancer (PRAGMATIC): quality of life and service use results.

Purpose: To describe trends and explore factors associated with quality of life (QoL) and psychological morbidity and assess breast cancer (BC) health service use over a 12-month period for patients joining the supported self-management (SSM)/patient-initiated follow-up (PIFU) pathway.

Methods: Participants completed questionnaires at baseline, 3, 6, 9 and 12 months that measured QoL (FACT-B, EQ 5D-5L), self-efficacy (GSE), psychological morbidity (GHQ-12), roles and responsibilities (PRRS) and service use (cost diary).

Results: 99/110 patients completed all timepoints; 32% (35/110) had received chemotherapy.

The SWAP Filter: A Simple Azimuthally Varying Radial Filter for Wide-Field EUV Solar Images.

Unlabelled: We present the SWAP Filter: an azimuthally varying, radial normalizing filter specifically developed for EUV images of the solar corona, named for the (SWAP) instrument on the (PROBA2) spacecraft. We discuss the origins of our technique, its implementation and key user-configurable parameters, and highlight its effects on data via a series of examples. We discuss the filter's strengths in a data environment in which wide field-of-view observations that specifically target the low signal-to-noise middle corona are newly available and expected to grow in the coming years.

Treatment of Cancer-Associated Thrombosis: Recent Advances, Unmet Needs, and Future Direction.

Cancer-associated thrombosis, with the incidence rising over the years, is associated with significant morbidity and mortality in patients with cancer. Recent advances in the treatment of cancer-associated venous thromboembolism (VTE) include the introduction of direct oral anticoagulants (DOACs), which provide a more convenient and effective option than low-molecular-weight heparin (LMWH). Nonetheless, important unmet needs remain including an increased risk of bleeding in certain patient subgroups such as those with gastroesophageal cancer, concerns about drug-drug interactions, and management of patients with severe renal impairment.

Brand-name market exclusivity for nebulizer therapy to treat asthma and COPD.

Nebulizer therapy is a cornerstone treatment for asthma and chronic obstructive pulmonary disease (COPD). We collected and analyzed all patents and regulatory exclusivities on brand-name nebulizer solutions approved for asthma and COPD from 1986–2020, quantified periods of protection from generic competition, and compared the patenting strategies employed by manufacturers of nebulizer versus inhaler therapy. The median duration of expected protection from generic competition for brand-name nebulizer solutions (n=13) was 7 years (after subtracting time lost to early generic entry), compared to 14 years for inhalers (n=53).

Patents And Regulatory Exclusivities On Inhalers For Asthma And COPD, 1986-2020.

Inhalers are the mainstay of treatment for asthma and chronic obstructive pulmonary disease (COPD). These products face limited generic competition in the US and remain expensive. To better understand the strategies that brand-name inhaler manufacturers have employed to preserve their market dominance, we analyzed all patents and regulatory exclusivities granted to inhalers approved by the Food and Drug Administration between 1986 and 2020.

Design, Synthesis, and Biological Characterization of Inhaled p38α/β MAPK Inhibitors for the Treatment of Lung Inflammatory Diseases.

The identification of novel inhaled p38α/β mitogen-activated protein kinases (MAPK) (MAPK14/11) inhibitors suitable for the treatment of pulmonary inflammatory conditions has been described. A rational drug design approach started from the identification of a novel tetrahydronaphthalene series, characterized by nanomolar inhibition of p38α with selectivity over p38γ and p38δ isoforms. SAR optimization of is outlined, where improvements in potency against p38α and ligand-enzyme dissociation kinetics led to several compounds showing pronounced anti-inflammatory effects (inhibition of TNFα release).

Discovery of a Novel Class of d-Amino Acid Oxidase Inhibitors Using the Schrödinger Computational Platform.

d-Serine is a coagonist of the -methyl d-aspartate (NMDA) receptor, a key excitatory neurotransmitter receptor. In the brain, d-serine is synthesized from its l-isomer by serine racemase and is metabolized by the D-amino acid oxidase (DAO, DAAO). Many studies have linked decreased d-serine concentration and/or increased DAO expression and enzyme activity to NMDA dysfunction and schizophrenia.

Early Utilization of Intravenous Immunoglobulin in Heparin-Induced Thrombocytopenia for Limb Salvaging Purposes.

We present a case of a 28-year-old diabetic female who presented with high-burden lower extremity deep vein thrombosis (DVT) after previous exposure to unfractionated heparin (UFH). Heparin was discontinued, and non-heparin parenteral anticoagulant, argatroban, was started based on a high clinical suspicion of heparin-induced thrombocytopenia with thrombosis (HITT). The diagnosis of HIT was later proven by positive immune and functional assays.

Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST).

Purpose: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital.

Characteristics of Clinical Trials Evaluating Biosimilars in the Treatment of Cancer: A Systematic Review and Meta-analysis.

Importance: Biologics account for almost half of US drug spending but may be subject to competitive pricing pressures by US Food and Drug Administration-approved biosimilars. The extent of the preapproval clinical testing that is needed and how these biosimilars compare with the originator biologic products remain critical issues in establishing a vibrant biosimilar market.

Objectives: To analyze the design of cancer biosimilar efficacy studies compared with the reference drug pivotal trials and provide summary risk ratio estimates for each cancer type drug subgroup.

Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa.

Background: Factor XI (FXI) inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of thromboembolic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI.

Objectives: To investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous and multiple dose subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively.

Impact of Hypofractionated Radiotherapy on Patient-reported Outcomes in Prostate Cancer: Results up to 5 yr in the CHHiP trial (CRUK/06/016).

Background: Moderate hypofractionation is the recommended standard of care for localised prostate cancer following the results of trials including Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP). Evaluation of long-term patient-reported outcomes (PROs) is important to confirm safety and enhance patient information.

Objective: To determine whether 5-yr PROs from the CHHiP quality of life (QoL) substudy confirm 2-yr findings and assess patterns over follow-up.

Factor XI Inhibition to Uncouple Thrombosis From Hemostasis: JACC Review Topic of the Week.

Hemostasis and thrombosis are believed to be so intricately linked that any strategies that reduce thrombosis will have an inevitable impact on hemostasis. Consequently, bleeding is viewed as an unavoidable side effect of anticoagulant therapy. Emerging evidence suggests that factor XI is important for thrombosis but has a minor role in hemostasis.

Abelacimab for Prevention of Venous Thromboembolism.

Background: The role of factor XI in the pathogenesis of postoperative venous thromboembolism is uncertain. Abelacimab is a monoclonal antibody that binds to factor XI and locks it in the zymogen (inactive precursor) conformation.

Methods: In this open-label, parallel-group trial, we randomly assigned 412 patients who were undergoing total knee arthroplasty to receive one of three regimens of abelacimab (30 mg, 75 mg, or 150 mg) administered postoperatively in a single intravenous dose or to receive 40 mg of enoxaparin administered subcutaneously once daily.