Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile.

Background: Biosimilar natalizumab (biosim-NTZ) is the first biosimilar monoclonal antibody of reference natalizumab (ref-NTZ) for treatment of relapsing forms of multiple sclerosis (MS). Within the totality of evidence for demonstration of biosimilarity, immunogenicity assessments were performed in healthy subjects and patients with relapsing-remitting MS (RRMS) to confirm a matching immunogenicity profile between biosim-NTZ and ref-NTZ.

Methods: Immunogenicity of biosim-NTZ versus ref-NTZ was evaluated in two pivotal clinical studies.

Follow-up Adherence After Teleretinal Screening for Diabetic Retinopathy.

Aim: Determine the follow-up rate for patients referred following an abnormal teleretinal imaging (TRI) screening and examine patient characteristics predictive of follow-up nonadherence.

Materials And Methods: A cross-sectional study of patients screened between August 2014 and July 2016 in the Harris Health System (HHS) in Houston, TX. All diabetic patients referred for in-person examination, who had data for all study variables, and who did not have established ophthalmic care in the HHS within the previous 2 years were included.

Accommodative behaviour and retinal defocus in highly myopic eyes fitted with a dual focus myopia control contact lens.

Purpose: To evaluate the myopic and hyperopic defocus delivered to the retina by a dual focus (DF) myopia control contact lens when myopia exceeds 6.00 D.

Methods: Individuals with high myopia were fitted bilaterally with high-powered DF lenses containing power profiles matching a Coopervision MiSight 1 day contact lens (omafilcon A) and a Coopervision Proclear 1 day single vision (SV) lens.

Intimidation against advocates and researchers in the tobacco, alcohol and ultra-processed food spaces: a review.

Unhealthy commodity industries (UCIs) engage in corporate political activity, using diverse practices, including intimidatory tactics, to thwart, delay and dilute regulations that threaten their businesses. While examples of such intimidation exist across multiple sectors, no attempt has been made to synthesize these. Furthermore, much of the literature focuses on intimidation of policy-makers.

Pharmacokinetic and pharmacodynamic similarity of biosimilar natalizumab (PB006) to its reference medicine: a randomized controlled trial.

Background: PB006 (Polpharma Biologics S.A; marketed as Tyruko®, Sandoz) is an approved biosimilar to natalizumab (Tysabri®; Biogen [ref-NTZ]). This multicenter, double-blind, randomized, single-dose study was conducted to demonstrate pharmacokinetic/pharmacodynamic (PK/PD) similarity between PB006 and ref-NTZ.

Six-year cumulative treatment effect and treatment efficacy of a dual focus myopia control contact lens.

Purpose: Accumulated axial growth observed during a 6-year clinical trial of a dual focus myopia control contact lens was used to explore different approaches to assess treatment efficacy.

Methods: Axial length measurements from 170 eyes in a 6-year clinical trial of a dual focus myopia control lens (MiSight 1 day, CooperVision) were analysed. Treatment groups comprised one having undergone 6 years of treatment and the other (the initial control group) having 3 years of treatment after 3 years of wearing a single vision control lens.

Six years of wearer experience in children participating in a myopia control study of MiSight® 1 day.

Purpose: To evaluate the experience of children wearing soft contact lenses (CLs) during a trial of MiSight® 1 day (omafilcon A, CooperVision, Inc.), a dual-focus myopia-control daily disposable CL.

Methods: A 3-year, double-masked, randomised trial (Part 1) comparing experiences with MiSight 1 day and a single-vision control (Proclear® 1 day, omafilcon A, CooperVision, Inc.

Myopia Control Dose Delivered to Treated Eyes by a Dual-focus Myopia-control Contact Lens.

Purpose: This study examined the optical impact of a DF contact lens during near viewing in a sample of habitual DF lens wearing children.

Methods: Seventeen myopic children aged 14 to 18 years who had completed 3 or 6 years of treatment with a DF contact lens (MiSight 1 Day; CooperVision, Inc., San Ramon, CA) were recruited and fit bilaterally with the DF and a single-vision (Proclear 1 Day; CooperVision, Inc.

A "willingness to be orchestrated": Why are UK diplomats working with tobacco companies?

Background: The tobacco epidemic is global and addressing it requires global collaboration. International and national policies have been adopted to promote collaboration for tobacco control, including an obligation on diplomatic missions to protect public health from the vested interests of the tobacco industry. However, incidents of diplomats engaging with the tobacco industry are still occurring despite these regulations.

An Integrative Data Analysis of Main and Moderated Crossover Effects of Parent-Mediated Interventions on Depression and Anxiety Symptoms in Youth in Foster Care.

Without preventative intervention, youth with a history of foster care (FC) involvement have a high likelihood of developing depression and anxiety (DA) symptoms. The current study used integrative data analysis to harmonize data across four foster and kinship parent-mediated interventions (and seven randomized control trials) designed to reduce youth externalizing and other problem behaviors to determine if, and for how long, these interventions may have crossover effects on youth DA symptoms. Moderation of intervention effects by youth biological sex, developmental period, number of prior placements, and race/ethnicity was also examined.

Molecular glue CELMoD compounds are regulators of cereblon conformation.

Cereblon (CRBN) is a ubiquitin ligase (E3) substrate receptor protein co-opted by CRBN E3 ligase modulatory drug (CELMoD) agents that target therapeutically relevant proteins for degradation. Prior crystallographic studies defined the drug-binding site within CRBN's thalidomide-binding domain (TBD), but the allostery of drug-induced neosubstrate binding remains unclear. We performed cryo-electron microscopy analyses of the DNA damage-binding protein 1 (DDB1)-CRBN apo complex and compared these structures with DDB1-CRBN in the presence of CELMoD compounds alone and complexed with neosubstrates.

Long-term Effect of Dual-focus Contact Lenses on Myopia Progression in Children: A 6-year Multicenter Clinical Trial.

Significance: Treatment of myopic children with a dual-focus soft contact lens (DFCL; MiSight 1 day) produced sustained slowing of myopia progression over a 6-year period. Significant slowing was also observed in children switched from a single vision control to treatment lenses (3 years in each lens).

Purpose: This study aimed to evaluate the effectiveness of DFCLs in sustaining slowed progression of juvenile-onset myopia over a 6-year treatment period and assess myopia progression in children who were switched to a DFCL at the end of year 3.

Anti-drug Antibody Validation Testing and Reporting Harmonization.

Evolving immunogenicity assay performance expectations and a lack of harmonized anti-drug antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. Following debate at the American Association of Pharmaceutical Sciences National Biotechnology Conference, a group was formed to address these gaps. Over the last 3 years, 44 members from 29 organizations (including 5 members from Europe and 10 members from FDA) discussed gaps in understanding immunogenicity assay requirements and have developed harmonization tools for use by industry scientists to facilitate filings to health authorities.

Structure of the human marker of self 5-transmembrane receptor CD47.

CD47 is the only 5-transmembrane (5-TM) spanning receptor of the immune system. Its extracellular domain (ECD) is a cell surface marker of self that binds SIRPα and inhibits macrophage phagocytosis, and cancer immuno-therapy approaches in clinical trials are focused on blocking CD47/SIRPα interaction. We present the crystal structure of full length CD47 bound to the function-blocking antibody B6H12.

Profiling CELMoD-Mediated Degradation of Cereblon Neosubstrates.

Targeted protein degradation is garnering increased attention as a therapeutic modality due in part to its promise of modulating targets previously considered undruggable. Cereblon E3 Ligase Modulating Drugs (CELMoDs) are one of the most well-characterized therapeutics employing this modality. CELMoDs hijack Cereblon E3 ligase activity causing neosubstrates to be ubiquitinated and degraded in the proteasome.

Avadomide induces degradation of ZMYM2 fusion oncoproteins in hematologic malignancies.

Thalidomide analogs exert their therapeutic effects by binding to the CRL4 E3 ubiquitin ligase, promoting ubiquitination and subsequent proteasomal degradation of specific protein substrates. Drug-induced degradation of IKZF1 and IKZF3 in B-cell malignancies demonstrates the clinical utility of targeting disease-relevant transcription factors for degradation. Here, we found that avadomide (CC-122) induces CRBN-dependent ubiquitination and proteasomal degradation of ZMYM2 (ZNF198), a transcription factor involved in balanced chromosomal rearrangements with and in aggressive forms of hematologic malignancies.

Axial length targets for myopia control.

Purpose: Both emmetropic and myopic eyes elongate throughout childhood. The goals of this study were to compare axial elongation among untreated progressing myopes, progressing myopes treated with a myopia control contact lens and emmetropes, in order to place axial elongation in the context of normal eye growth in emmetropic children, and to consider whether normal physiological eye growth places limits on what might be achieved with myopia control.

Methods: Axial elongation data were taken from the 3-year randomised clinical trial of a myopia control dual-focus (MiSight® 1 day) contact lens.

Optic nerve biopsy in leukemic infiltrative optic neuropathy: a case report and review of the literature.

Optic nerve infiltration is a rare but known complication of the central nervous system (CNS)-involving lymphoma and leukemic disorders. The diagnosis is often presumed and patients are empirically treated with systemic therapy and/or local radiation. Optic nerve biopsy is usually avoided due to the risk of permanent vision loss secondary to the procedure.