Canada approved its first generic version of semaglutide on April 28, 2026, 114 days after market exclusivity on the brand-name product expired and 26 months after the first generic company filed. Neither Health Canada nor the manufacturers appear to have missed a regulatory deadline. The delay arose because Health Canada had never set out how a manufacturer should establish that a fully synthetic semaglutide is the same drug as a semisynthetic reference product, so the agency and the companies settled that evidentiary standard one round of review at a time. Canadians paying out-of-pocket spent more than $160 extra per month across roughly 4 months, while public payers lost discounts that confidential rebate agreements make impossible to quantify. We argue that Health Canada should publish up-front equivalence standards for complex generic products, starting with synthetic peptides, so the next manufacturer can build the required evidence into its first submission. Any regulator that has not defined an equivalence standard for complex generics before the relevant exclusivities lapse may face similar delays, and a growing number of high-income countries will confront that question as peptide products lose protection.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination, and neurodegeneration, associated with a complex interplay between the innate and adaptive immune systems. Currently, no cure is available for MS, and personalized disease-modifying treatment remains largely limited, partially due to the lack of preclinical human models that can faithfully recapitulate disease pathology and evaluate treatment responses at the individual-patient level. Here, we report a human myelin microphysiological system (myelin MPS) platform that recaptures disease phenotype and treatment response for testing patient treatment response. By culturing neural organoids on 3D-printed devices containing directional microfibers, followed by coculture with oligodendrocyte progenitor cells, 96 myelin MPS models can be generated within a conventional well plate. Using this myelin MPS platform, autologous T cells and monocytes from MS patients induced substantially greater demyelination than those from healthy donors, accompanied by expansion of proinflammatory T-cell subsets and increased myelin uptake by monocytes/macrophages after coculture with these healthy myelinating neural tissues. Integration of imaging and flow-cytometric features distinguished healthy-donor, untreated-MS, responder, and nonresponder profiles following treatment with prednisone, glatiramer acetate, interferon β-1a, or dimethyl fumarate. Thus, the myelin MPS platform provides a scalable, human pathophysiology-relevant platform for functional phenotyping and individualized treatment-response evaluation in MS.

Disease-modifying therapies (DMTs) for multiple sclerosis (MS) can be either high- or low-intensity. This study aims to examine predictors associated with high-intensity MS treatment strategies using commercial claims data.

The multiple sclerosis (MS) therapeutic landscape has evolved over time. We conducted a knowledge graph-guided analysis of MS-specific disease-modifying therapy (DMT) prescription trends using longitudinal real-world clinical data. We analyzed registry-linked electronic health record (EHR) data from two large independent healthcare systems between 2004 and 2022, including both academic and community practices. We developed an unsupervised phenotyping algorithm that leverages a publicly available knowledge graph and informative EHR features to identify patients with MS. After identifying MS cases, we combined the two cohorts and constructed annual time-varying knowledge graphs that capture co-occurrence patterns between DMTs and MS diagnosis. For each year, we analyzed co-occurrence patterns between DMTs and MS diagnosis using Shifted Positive Pointwise Mutual Information transformation and singular value decomposition to generate embeddings. We computed patient-wise cosine similarities and confidence intervals to quantify MS-specific DMT usage patterns. The phenotyping algorithm achieved robust performance in predicting MS diagnosis (AUROC: MGB = 0.994, UPMC = 0.922), identifying 29,169 MS patients in the combined dataset. Among commonly used standard-effectiveness DMTs, MS-specific prescriptions declined after 2011 for interferon-beta (DMT-MS cosine similarity slope = -0.019 ± 0.011, p = 0.002) and glatiramer acetate (slope = -0.013 ± 0.012, p = 0.026), from 2013-2020 for fumarates (slope = -0.028 ± 0.015, p = 0.004), and after 2014 for S1P receptor modulators (slope = -0.026 ± 0.016, p = 0.005). Among commonly used higher-effectiveness DMTs, B-cell depletion therapies (slope = 0.051 ± 0.027, p = 0.001), particularly ocrelizumab (slope = 0.020 ± 0.016, p =0.032), showed a marked increase since 2018. Natalizumab usage peaked in 2011 (slopepre-2011 = 0.063 ± 0.013, ppre-2011 < 0.001; slopepost-2011= -0.027 ± 0.008, ppost-2011 < 0.001). Other DMT classes such as cell proliferation inhibitors and chemotherapy agents, showed low usage during follow-up. These findings provide real-world evidence from two large EHR-based MS cohorts, highlighting distinct temporal shifts in the complex MS therapeutic landscape toward higher-effectiveness DMTs, particularly B-cell depletion therapy.

Peripheral nerve injury (PNI) and spinal cord injury (SCI) impose a major burden of traumatic neurological disability worldwide. Autologous nerve grafting, the current gold standard, achieves meaningful recovery in only 81.6% of repairs (2023 meta-analysis, n = 1,559), while hollow nerve graft conduits achieve only 62.2% (p < 0.05), with performance declining sharply beyond 20-30 mm gaps. Passive scaffolds cannot counter the inhibitory post-injury microenvironment of reactive gliosis, chondroitin sulfate proteoglycan (CSPG) deposition, oxidative stress, and myelin-associated inhibitors, which actively collapse regenerating axon growth cones. This review traces the conceptual and developmental logic of a family of bioactive hydrogels, "neurogels", designed as active modulators of the regenerative microenvironment rather than passive bridges. We organize the review around the scientific problem: the biological barriers that passive scaffolds cannot address; the design rationale for a hyaluronic acid (HA)-based neurogel bearing a biomimetic laminin-derived peptide (LDP-916), an antioxidant, and an antigliotic immunomodulator; the formulation evolution from the original Guiding Regenerative Gel (GRG; HA + LDP-916 + recombinant superoxide dismutase 1, SOD1) to the current Antigliotic Guiding Regenerative Gel (AGRG; HA + LDP-916 + DL-α-tocopherol + glatiramer acetate); and the preclinical evidence base. An in vitro [35]S-glycosaminoglycan candidate-selection screen in activated astrocytes identified several antigliotic agents; translational barriers of the top-ranked biologics (bacterial origin and thermolability of chondroitinase ABC; blood-brain barrier impermeability of anti-NogoA antibody) motivated selection of glatiramer acetate, the active copolymer of Copaxone (a clinically validated multiple sclerosis drug), and replacement of SOD1 by DL-α-tocopherol for manufacturing and stability reasons. AGRG increased neurite length by approximately 78% in vitro relative to control, showed electrophysiological performance comparable to or exceeding autograft in a 25 mm chronic rabbit PNI model at 40 weeks, and promoted myelinated axon regrowth in acute and chronic rat SCI. A recently completed 15 mm rat sciatic critical-gap study comparing AGRG to autograft provides supportive internal data; because this dataset has not yet completed independent peer review, its findings are described in general terms and are not used as a basis for definitive efficacy claims. Regulatory-enabling studies are being pursued by Maxonis Ltd. in preparation for an FDA pre-IND interaction.

Glatiramer is the active portion of the drug, glatiramer acetate. No information is available on the excretion of glatiramer acetate into breastmilk. However, data from the manufacturer indicates that after subcutaneous injection, glatiramer undergoes rapid degradation to amino acids and shorter peptides and that it cannot be detected in the plasma, urine or feces.[1] Furthermore, any glatiramer that did reach the breastmilk would probably be destroyed in the infant's gastrointestinal tract and not absorbed, except perhaps in neonates. Follow-up of infants indicates that maternal use of glatiramer acetate does not appear to cause any adverse effects in breastfed infants. Glatiramer acetate is generally considered safe by most experts and appears to be one of the preferred disease-modifying agents for treating multiple sclerosis during breastfeeding.[2-7]