Laura Witt, from St. Joseph Hospital at Ruhr University in Bochum, Germany, and colleagues examined infant development during the first 36 months of life for infants of mothers receiving mAb for multiple sclerosis. A total of 183 mAb breastfed-exposed infants whose mothers had a diagnosis of multiple sclerosis or neuromyelitis optica spectrum disease were compared to 183 unexposed infants (controls). mAb exposure during breastfeeding started on a median of 19 days postpartum.

Breastfeeding participants most often received natalizumab, followed by ocrelizumab, rituximab, and ofatumumab (68.31, 18.58, 6.01, and 5.46%, respectively); while breastfeeding, 2 cases switched from natalizumab to ocrelizumab and one from rituximab to ocrelizumab. The researchers found that annual infant hospitalization, annual systemic antibiotic use, developmental delay, or weight at follow-up visits were not associated with mAb-exposed breastfeeding.

“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first three years of life,” coauthor Kerstin Hellwig, MD, also from St. Joseph Hospital, said in a statement.

The study was partly funded by pharmaceutical companies.

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Briumvi (ublituximab-xiiy) is now available for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

The CD20-directed cytolytic antibody therapy was approved based on data from two phase 3 trials that showed treatment with Briumvi led to a significant reduction in annualized relapse rate over a 96-week period compared with teriflunomide. The most common adverse reactions reported with treatment included infusion reactions and upper respiratory tract infections.

Briumvi is administered as an intravenous infusion under the close supervision of an experienced health care professional with access to appropriate medical support to manage severe reactions, such as serious infusion reactions. Prior to initiating therapy, patients should undergo hepatitis B virus screening and serum immunoglobulin testing. Any necessary vaccines should also be administered at least 4 weeks (for live or live-attenuated) or 2 weeks (nonlive) prior to starting Briumvi.

Additionally, patients should be assessed for active infection before every infusion and pregnancy testing is recommended for females of reproductive potential. Premedication with methylprednisolone (or an equivalent corticosteroid) and an antihistamine (eg, diphenhydramine) can help reduce the frequency and severity of infusion reactions.

Following the first infusion of Briumvi, a second infusion is administered 2 weeks later; a subsequent infusion is administered 24 weeks after the first infusion and then every 24 weeks thereafter. Patients should be monitored closely for at least 1 hour after completing the first 2 infusions; for subsequent infusions, monitoring is at physician discretion.

Briumvi is supplied as a 150mg/6mL single-dose vial containing a preservative-free solution for intravenous use.

To help patients gain access to treatment, TG Therapeutics has established the Briumvi Patient Support program.

References

1. TG Therapeutics announces commercial launch of Briumvi (ublituximab-xiiy) for the treatment of adult patients with relapsing forms of multiple sclerosis. News release. January 26, 2023. https://www.globenewswire.com/news-release/2023/01/26/2595890/8790/en/TG-Therapeutics-Announces-Commercial-Launch-of-BRIUMVI-ublituximab-xiiy-for-the-Treatment-of-Adult-Patients-with-Relapsing-Forms-of-Multiple-Sclerosis.html.
2. Briumvi. Package insert. TG Therapeutics; 2022. Accessed January 26, 2023. https://www.tgtherapeutics.com/label-prescribing-info/uspi-briumvi.pdf.

The Food and Drug Administration (FDA) has approved Tyruko^® (natalizumab-sztn), a biosimilar to Tysabri (natalizumab).

Tyruko is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. This is the first biosimilar product indicated for treating relapsing forms of MS.

The approval was based on a robust data package that included phase I and phase 3 clinical studies. Findings from the phase 3 Antelope study (ClinicalTrials.gov Identifier: NCT04115488) in RRMS patients showed that the biosimilar product was equivalent in efficacy, safety and immunogenicity to the reference product.

“Today’s approval of the first biosimilar product indicated to treat relapsing forms of multiple sclerosis furthers the FDA’s longstanding commitment to support a competitive marketplace for biological products and ultimately empowers patients by helping to increase access to safe, effective and high-quality medications at potentially lower cost,” said Sarah Yim, M, director of the Office of Therapeutic Biologics and Biosimilars in the FDA’s Center for Drug Evaluation and Research.

Tyruko is also approved for inducing and maintaining clinical response and remission in adult patients with moderately to severely active Crohn disease (CD) with evidence of inflammation who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-α.

Like the reference product, the prescribing information for Tyruko includes a Boxed Warning regarding the risk of progressive multifocal leukoencephalopathy (PML). Because of the risk of PML, Tyruko is only available through a restricted distribution program called the Tyruko REMS Program.  When initiating and continuing treatment, clinicians should consider whether the expected benefit of Tyruko is sufficient to offset the risk of PML.

Tyruko is supplied as a 300mg/15mL solution in a single-dose vial for dilution prior to infusion.

Acthar^® Gel is indicated:

• As monotherapy for the treatment of infantile spasms in infants and children under 2 years of age; 
• For the treatment of exacerbations of multiple sclerosis in adults; and
• May be used for the following disorders and diseases: rheumatic; collagen; dermatologic; allergic states; ophthalmic; respiratory; and edematous state.

According to the Company, the new injector device is intended to allow adults to self-administer Acthar Gel with fewer steps and designed to help patients with dexterity issues. The device is for subcutaneous administration only and features a hidden needle to prevent needlestick injuries in users.

Acthar Gel single-dose prefilled SelfJect Injector is supplied as 40 USP Units/0.5mL and 80 USP Units/mL dosage strengths in a 4-count carton and is expected to be available in the second half of 2024. Acthar Gel is currently available in a 5mL multi-dose vial (80 USP Units/mL).

“We’re excited to bring this innovation to US patients with chronic and acute inflammatory and autoimmune conditions,” said Peter Richardson, MRCP (UK), Executive Vice President and Chief Scientific Officer. “This approval reflects Mallinckrodt’s longstanding commitment to clinical research and therapeutic modernization efforts providing a new delivery device for patients, caregivers, and medical professionals managing these challenging conditions.” 

GA Depot 40mg is a long-acting version of FDA-approved Copaxone intended to be administered intramuscularly (IM) once every 4 weeks. Glatiramer acetate is thought to act by modifying immune processes that are believed to be responsible for the pathogenesis of MS.

The application included data from a randomized, double-blind phase 3 trial (ClinicalTrials.gov Identifier: NCT04121221) that evaluated the efficacy and safety of GA Depot 40mg in 1016 adults with RMS. Study participants were randomly assigned to receive either GA Depot 40mg or placebo via IM injection every 4 weeks for a total of 13 doses. 

Findings showed that treatment with GA Depot statistically significantly reduced annualized relapse rate (primary endpoint) by 30.1% compared with placebo (P =.0066). The most common adverse reaction reported with GA Depot was injection site reaction.

The CRL delays the decision on approval for GA Depot 40mg. The Companies are reviewing the letter to determine next steps.

KYV-101 is an autologous, fully human CD19 chimeric antigen receptor (CAR) T-cell therapy designed to deplete B cells, including autoreactive B cells, in patients with autoimmune diseases. The product will be evaluated in a phase 2, open-label trial (KYSA-7) that will enroll patients with treatment-refractory progressive MS.

“We appreciate the FDA’s support to accelerate the development of potentially life-changing CAR T-cell therapies that could greatly benefit patients living with severe and debilitating neurological autoimmune diseases,” said Peter Maag, PhD, CEO of Kyverna. “This marks another important milestone in our endeavor to change the treatment paradigm with KYV-101.”

The Company is investigating KYV-101 for the treatment of multiple autoimmune diseases including lupus nephritis, myasthenia gravis and scleroderma.

The FDA’s Fast Track designation helps to accelerate the development and review of products for serious and life-threatening conditions where no treatment exists or where the investigational therapy is likely to provide an advantage over currently available treatments.

Octave Guinebretiere, from Sorbonne Université in Paris, and colleagues examined the association between diseases and symptoms diagnosed in primary care and the risk for MS relative to controls and 2 other autoimmune inflammatory diseases (lupus and Crohn disease) in a case-control study. The study population included 20,174 patients with MS; 54,790 patients without MS; 30,477 patients with Crohn disease; and 7337 patients with lupus.

The researchers observed significant positive associations for 12 International Classification of Diseases, 10th Revision (ICD-10) codes with the risk for MS compared with controls without MS. Five codes remained significantly associated with MS after considering ICD-10 codes suggestive of neurological symptoms as the first diagnosis of MS: depression, sexual dysfunction, constipation, cystitis, and urinary tract infections of unspecified site (odds ratios, 1.22, 1.47, 1.50, 1.21, and 1.38, respectively). In comparisons with lupus and Crohn disease, none of these conditions was selectively associated with MS. During the 5 years after diagnosis, all 5 ICD-10 codes identified were still associated with MS.

“Due to the frequency of these symptoms in the general population and the nonspecificity regarding prodrome in other autoimmune diseases, we should not expect that the identification of a prodrome will dramatically change clinical care, at least in the general population,” the authors write.

Several authors disclosed ties to the pharmaceutical industry.

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Patrick Vermersch, MD, PhD, from the University of Lille in France, and colleagues conducted a phase 2, double-blind trial to examine frexalimab treatment for relapsing multiple sclerosis. Patients were assigned to receive 1200mg of frexalimab administered intravenously every 4 weeks, 300mg frexalimab administered subcutaneously every 2 weeks, or the matching placebos for each active treatment in a 4:4:1:1 ratio; 125 patients completed the 12-week double-blind period.

The researchers found that the adjusted mean number of new gadolinium-enhancing T1-weighted lesions was 0.2 and 0.3 in the groups that received 1200 and 300mg frexalimab, respectively, compared with 1.4 in the pooled placebo group. Compared with placebo, the rate ratios were 0.11 and 0.21 in the 1200 and 300mg frexalimab groups, respectively. For secondary imaging end points, the results were generally in the same direction as those for the primary analysis. COVID-19 and headaches were the most common adverse events.

“Treatment with the anti-CD40L monoclonal antibody frexalimab had a generally favorable effect, as compared with placebo, on the number of new gadolinium-enhancing T1-weighted lesions at week 12,” the authors write. “Larger and longer trials are needed to determine the long-term efficacy and safety of frexalimab in persons with relapsing multiple sclerosis.”

The study was funded by Sanofi, which is developing frexalimab.

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Sifat Sharmin, PhD, from the University of Melbourne in Australia, and colleagues examined how high-efficacy therapies influence transition across 5 disability states in individuals with pediatric-onset multiple sclerosis. Data were included from 151 centers across 41 countries. People with onset of multiple sclerosis symptoms at younger than 18 years were included if they had a confirmed diagnosis of relapsing-remitting multiple sclerosis and at least 4 Expanded Disability Status Scale scores recorded. Overall, 5224 patients were included.

The researchers observed a reduction in the risk for disability worsening across the disability states with high-efficacy therapies. Compared with those who remained untreated, those treated with high-efficacy therapies while in the minimal disability state had the largest reduction (hazard ratio, 0.41). There was a decline seen in the benefit of high-efficacy therapies with increasing disability. Compared with those who remained untreated, young people with minimal disability who received low-efficacy therapy also experienced a reduced risk for transitioning to mild disability (hazard ratio, 0.65).

“The new perspective presented here on the effect of early high-efficacy therapies for preserving neurological function among people with pediatric-onset multiple sclerosis provides a useful addition to the information guiding policy governing access to disease-modifying therapies in children with multiple sclerosis,” the authors write.

Several authors disclosed ties to the biopharmaceutical industry.

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Positive data were announced from a phase 3 trial evaluating an investigational subcutaneous (SC) formulation of ocrelizumab in patients with multiple sclerosis.

Ocrelizumab, a CD20-directed cytolytic antibody, is currently marketed under the brand name Ocrevus^® as a solution for IV infusion. The global, multicenter, randomized, open-label, parallel group OCARINA II study (ClinicalTrials.gov Identifier: NCT05232825) compared the efficacy and safety of a 10-minute SC injection of ocrelizumab to IV infusion of ocrelizumab in 236 adults with relapsing MS or primary progressive MS. 

The primary endpoint of the study was noninferiority in serum area under the curve (AUC) from day 1 to 12 weeks after SC injection compared with IV infusion. Secondary endpoints included maximum serum concentration of ocrelizumab, the total number of active, gadolinium-enhancing T1 lesions at 8 and 12 weeks, and new or enlarging T2 lesions at 12 and 24 weeks.

Findings showed that SC injection of ocrelizumab was noninferior to ocrelizumab administered by IV infusion for AUC over 12 weeks. Additionally, the 2 formulations were found to be similar with regard to controlling magnetic resonance imaging (MRI) lesion activity in the brain over 12 weeks. Adverse events were observed to be consistent across both groups.

“These results give people living with MS the possibility to receive the transformational benefits of Ocrevus in the way best suited to their lives while freeing up time and healthcare resources,” said Levi Garraway, MD, PhD, Genentech’s chief medical officer and head of Global Product Development. “This new subcutaneous injection will allow Ocrevus to be administered in 10 minutes twice a year, helping people living with MS to spend less time in treatment for this disease.’’

The table below is a review of notable updates that occurred in July 2023 for investigational products in development (not an inclusive list). Click on the status to view our full coverage.

The Food and Drug Administration (FDA) has accepted for review the New Drug Application for glatiramer acetate (GA) Depot 40mg for the treatment of relapsing forms of multiple sclerosis (RMS).

GA Depot 40mg is a long-acting version of FDA-approved Copaxone intended to be administered intramuscularly (IM) once every 4 weeks. The application is supported by data from a randomized, double-blind phase 3 trial (ClinicalTrials.gov Identifier: NCT04121221), which evaluated the efficacy and safety of GA Depot 40mg in 1016 adults with RMS. Study participants were randomly assigned to receive either GA Depot 40mg or placebo via IM injection every 4 weeks for a total of 13 doses.

Results showed that treatment with GA Depot statistically significantly reduced annualized relapse rate (primary endpoint) by 30.1% compared with placebo (P =.0066). Key secondary endpoints were also met with a 28.5% reduction in cumulative T1 new enhancing lesions (P =.0083); a 17.3% reduction in cumulative new or newly enlarging hyperintense T2 lesions at week 52 (P =.0305); and a significant reduction in mean expanded disability status scale score (P =.0193). The most common adverse reaction reported with GA Depot was injection site reaction.

“We are confident that GA Depot, when approved, will represent an important advancement in MS care by offering a convenient once-monthly option for patients which may potentially improve compliance and adherence, and the medicine is well positioned to deliver on this important unmet need,” said Ehud Marom, CEO and Chairman, Mapi Pharma.

A regulatory decision is expected on March 8, 2024.