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.

Press Release

More Information

HealthDay News — For adults with radiologically isolated syndrome (RIS), teriflunomide is associated with a reduction in the first clinical demyelinating event compared with placebo, according to a study presented at the annual meeting of the American Academy of Neurology, held from April 22 to 27 in Boston.

Christine Lebrun Frenay, MD, from the University Hospital of Nice in France, and colleagues randomly assigned 89 patients with RIS to teriflunomide or placebo in a phase III study. Participants underwent follow-up at weeks 48 and 96.

The researchers detected 28 clinical events during follow-up (20 with placebo; 8 with teriflunomide). The superiority of teriflunomide was demonstrated in unadjusted and adjusted analyses (hazard ratios, 0.38 and 0.34, respectively). The teriflunomide arm had a reduction in the number of patients with gadolinium+ lesions and the cumulative number of new or enlarging T2 lesions, although these results were not statistically significant.

“Our findings suggest that early intervention with teriflunomide may be beneficial to those diagnosed with radiologically isolated syndrome, the presymptomatic phase of multiple sclerosis,” Lebrun Frenay said in a statement. “However, more research is needed in larger groups of people to confirm our findings. Additionally, it is important that medical professionals are cautious when using MRI expertise to diagnose this condition, selecting only patients at risk of developing multiple sclerosis and not increasing MRI misdiagnoses.”

The study was funded by Sanofi, which manufactures teriflunomide.

Press Release

More Information

The Food and Drug Administration (FDA) has approved the Proclaim XR spinal cord stimulation (SCS) system for the treatment of painful diabetic peripheral neuropathy.

The Proclaim XR SCS system consists of an implantable pulse generator that delivers electrical pulses through leads to nerves along the spinal cord.  It was originally approved in 2019 for the treatment of chronic pain.

Clinical studies have shown that SCS treatment in patients with painful diabetic peripheral neuropathy (PDPN) can lead to significant reduction in pain and improved quality of life. When compared with conventional medical treatment alone, the addition of SCS reduced pain more effectively in patients with PDPN in the lower limbs.

Prior to implanting the SCS, a stimulation trial should be performed on a patient to confirm satisfactory pain relief. Patients who successfully complete the trial and undergo implantation of the Proclaim XR SCS device can then control their therapy using an Apple device. The system also pairs with Abbott’s NeuroSphere Virtual Clinic, allowing individuals to communicate with a clinician via a secure in-app video chat and receive remote programming adjustments.

Commenting on the expanded approval, Pedro Malha, vice president, neuromodulation, Abbott, said: “This new indication for Proclaim XR will drive meaningful change in the treatment of pain associated with diabetic peripheral neuropathy and will be an important tool for physicians and patients in managing this debilitating condition.”

Reference

FDA approves Abbott’s spinal cord stimulation for people living with painful diabetic peripheral neuropathy. News release. January 26, 2023. https://www.prnewswire.com/news-releases/fda-approves-abbotts-spinal-cord-stimulation-for-people-living-with-painful-diabetic-peripheral-neuropathy-301731127.html

The Food and Drug Administration (FDA) has cleared Abbott’s Liberta RC deep brain stimulation (DBS) system for individuals with movement disorders.

The Liberta RC DBS system is indicated for the following:

• Bilateral stimulation of the subthalamic nucleus or the internal globus pallidus as an adjunctive therapy to reduce some of the symptoms of advanced levodopa-responsive Parkinson disease that are not adequately controlled by medications.
• Unilateral or bilateral stimulation of the ventral intermediate nucleus of the thalamus for the suppression of disabling upper extremity tremor in adult essential tremor patients whose tremor is not adequately controlled by medications and where the tremor constitutes a significant functional disability.

According to Abbott, Liberta RC DBS is the smallest rechargeable DBS device on the market with remote programming, approximately the “height and width of a smartwatch face”. Under standard settings, the system requires the fewest recharges, at 10 recharge sessions a year, for most users using a wireless charger system that is placed over the device. For users who prefer a weekly charging schedule, the system needs 30 minutes to charge.

The Liberta RC DBS system works with Abbott’s NeuroSphere Virtual Clinic, which allows individuals to communicate remotely with physicians, ensure proper settings and functionality, and receive new treatment settings. 

Users will be able to control the system via an Abbott supplied patient controller or a secure, compatible iOS device. 

Xcopri tablets can now either be swallowed whole or be crushed. The crushed tablet can be mixed with water and either administered by mouth as an oral suspension or administered via a nasogastric tube. 

The labeling update is supported by data from an open-label, randomized, single-center, 3-period, 6-sequence, balanced crossover study. Findings showed the plasma Cmax and AUC for Xcopri crushed tablets mixed in water, administered either orally or through a nasogastric tube, were similar to whole tablets.

“The approval addresses the needs of patients living with epilepsy who are currently taking, or who may benefit from starting Xcopri, but are unable to swallow the tablets whole,” said Louis Ferrari, BS, RPh, MBA, vice president, Medical Affairs at SK Life Science. “In some patients, crushing tablets offers an additional option for dosing and administration by nasogastric tube. This label update addresses an unmet need for this patient population and offers administration alternatives to the health care providers managing their care.”

Xcopri is available as 12.5mg-, 25mg-, 50mg-, 100mg-, 150mg-, and 200mg-strength tablets.

HealthDay News — Neurodevelopment and growth in offspring is not negatively impacted by prenatal exposure to attention-deficit/hyperactivity disorder (ADHD) medication, according to a study published online February 9 in Molecular Psychiatry.

Kathrine Bang Madsen, PhD, from Aarhus University in Denmark, and colleagues assessed whether in utero exposure to ADHD medication was associated with adverse long-term neurodevelopmental and growth outcomes in offspring. The analysis included 898 children exposed to ADHD medication in utero and 1270 children whose mothers discontinued ADHD medication before pregnancy, who were born from 1998 to 2015 and followed through 2018.

After adjusting for demographic and psychiatric characteristics of the mother, the researchers observed no increased risk for any offspring developmental disorders for either combined (adjusted hazard ratio, 0.97; 95% CI, 0.81 to 1.17) or separate subcategories. In the negative control and sibling-controlled analyses, there was no increased risk seen for any subcategories of outcomes.

“We can see that the number of women of childbearing age who are medicated for ADHD is rapidly increasing, and therefore it is very important to garner more knowledge to be able to counsel these women,” a coauthor said in a statement. “There are still unknowns, but these results may contribute to women making informed decisions about using ADHD medication during pregnancy.”

Several authors disclosed financial ties to the pharmaceutical industry.

Abstract/Full Text (subscription or payment may be required)

Vamorolone is a novel corticosteroid that acts through the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The precise mechanism by which vamorolone exerts its effect in patients with DMD is unknown. 

The approval was based on data from the randomized, double-blind, placebo- and active-controlled phase 2b VISION-DMD study (ClinicalTrials.gov Identifier: NCT03439670), which evaluated the efficacy and safety of vamorolone in ambulant boys 4 to less than 7 years of age with DMD. Patients (N=121) were randomly assigned to receive vamorolone orally at daily doses of 2mg/kg or 6mg/kg, prednisone 0.75mg/kg/day, or placebo.

Treatment with vamorolone 6mg/kg/day met the primary endpoint demonstrating superiority in change from baseline in time to stand test (TTSTAND) velocity at 24 weeks vs placebo (treatment difference, 0.06 [95% CI, 0.023-0.098] rises/second from baseline [P =.002]). This corresponded to a clinically relevant improvement in TTSTAND in the vamorolone 6mg/kg/day arm (from 6.0 to 4.6 seconds) and deterioration in the placebo arm (from 5.4 to 5.5 seconds).

Vamorolone was also found to be superior to placebo across multiple secondary endpoints, including TTSTAND velocity for 2mg/kg/day (P =.02), 6-minute walk test (6MWT) for 6mg/kg/day (P =.002) and 2mg/kg/day (P =.004), and time to run/walk 10 meters (TTRW) for 6mg/kg/day (P =.002).

No statistically significant differences were observed between vamorolone 6mg/kg/day and prednisone across all endpoints. The analysis showed that height percentile declined in patients treated with prednisone but not among those who received vamorolone (P =.02).

The use of vamorolone in patients 2 years to less than 4 years of age and 7 to less than 18 years of age is supported by findings of efficacy and safety in patients 4 to less than 7 years of age with DMD and by pharmacokinetic and safety data.

The most common adverse reactions reported were cushingoid features, psychiatric disorders, vomiting, increased weight, and vitamin D deficiency. The prescribing information includes warnings and precautions related to alterations in endocrine function, immunosuppression and increased risk of infection, alterations in cardiovascular and renal function, gastrointestinal perforation, behavioral and mood disturbances, and effects on bones and eyes.

Agamree is supplied as a 40mg/mL oral suspension. The product is expected to be available in the first quarter of 2024. Prior to starting treatment, all age-appropriate immunizations should be administered.

HealthDay News — Xanthine dehydrogenase/oxidase blockers may reduce the risk for neurodegenerative diseases, according to a study published online May 17 in PLOS ONE.

Yizhe Song, from the Washington University School of Medicine in St. Louis, and colleagues conducted a population-based, case-control study of US Medicare beneficiaries in 2009 to identify prescription medications associated with a lower risk for 3 neurodegenerative diseases: Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. The analysis included 42,885 patients with neurodegenerative disease and 334,387 randomly selected controls. All filled medications were categorized according to their biological targets and mechanisms of action of those targets using medication data from 2006 to 2007. The odds ratios were estimated for 141 target-action pairs and each neurodegenerative disease. For target-action pairs inversely associated with diseases, replication was attempted in a cohort, including an active comparator group.

The researchers found that the most consistent inverse association across all 3 neurodegenerative diseases was for xanthine dehydrogenase/oxidase blockers, tied to the gout medication allopurinol. In multinomial regression, allopurinol was associated with a 13 to 34% lower risk for each neurodegenerative disease group and a mean reduction of 23% overall compared with those not using allopurinol. In the replication cohort, there was a 23% reduction for neurodegenerative diseases observed in the fifth year of follow-up comparing allopurinol users versus nonusers; with an active comparator group, more marked associations were seen.

“The medication associations we studied relate to disease risk,” a coauthor said in a statement. “Further research will be necessary to examine whether this mechanism slows progression of these diseases.”

Abstract/Full Text

Approved in September 2022, Relyvrio is an oral, fixed-dose coformulation of sodium phenylbutyrate and taurursodiol, also known as ursodoxicoltaurine. The approval was based on data from the phase 2 CENTAUR trial (ClinicalTrials.gov Identifier: NCT03127514), which showed Relyvrio significantly slowed the loss of physical function in patients with ALS compared with placebo.

However, topline results from the phase 3 PHOENIX trial (ClinicalTrials.gov Identifier: NCT05021536) showed the treatment was not associated with a statistically significant difference from baseline in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale total score at week 48 compared with placebo (primary endpoint). Moreover, statistically significant differences were not observed across secondary endpoints. Additional data from the trial will be presented at the American Academy of Neurology annual meeting this month.

The Company has decided to provide Relyvrio through a free drug program for those who wish to stay on therapy. It will no longer be available to new patients. The open-label extension portion of the PHOENIX trial remains ongoing.

“The decision to remove [Relyvrio] from the market and provide therapy free of charge for those who wish to continue was informed by the PHOENIX trial results, engagement with regulatory authorities, and discussions with the ALS community,” said Joshua Cohen and Justin Klee, Co-CEOs of Amylyx.

The Company has started the process with the Food and Drug Administration to discontinue marketing authorization for Relyvrio.

Alzheimer Dementia Treatments

HealthDay News — Amygdala and insula retraining (AIR), a neuroplasticity program, may be a viable means of reducing fatigue and increasing energy among patients with long COVID, according to a study published online July 17 in the Evidence-Based Complementary and Alternative Medicine Journal.

Loren L. Toussaint, PhD, from Luther College in Decorah, Iowa, and Alexandra J. Bratty, MBA, PhD, from AB Research Consulting in Las Vegas, randomly assigned 100 participants (aged 21 to 65 years) with postviral symptoms at least 3 months after an acute COVID-19 infection to AIR or control.

The researchers found a significant decrease in participants’ fatigue and a significant increase in their energy after the 3-month AIR intervention. Fatigue reduction was nearly 4 times higher in the AIR group vs the control group, while the absolute reduction in mean scores for the AIR group was more than double that of the control group. Similarly, the effect size in energy enhancement among AIR participants was twice that of the control group, and the absolute increase in energy mean scores for the AIR group was almost double that of the control group.

“These findings are both timely and pertinent, as so little is known about how to treat long COVID and so many patients suffer from it after the acute infection of COVID-19,” the authors write.

Bratty is the CEO of AB Research Consulting, which provides consulting services to The Gupta Program, the commercial version of the AIR intervention; Bratty’s company was compensated for this work by independent donors.

Abstract/Full Text

The Food and Drug Administration (FDA) has granted Fast Track designation to ACI-24.060, an anti-amyloid beta (Abeta) active immunotherapy candidate for the treatment of Alzheimer disease.

By enhancing the formation of polyclonal anti-Abeta antibodies, ACI-24.060 is expected to inhibit plaque accumulation and increase plaque clearance, thereby potentially reducing or preventing Alzheimer disease progression.

The designation was supported by initial interim safety and immunogenicity data from the phase 1b/2 ABATE trial (ClinicalTrials.gov Identifier: NCT05462106), a double-blind, placebo-controlled study assessing ACI-24.060 in patients with prodromal Alzheimer disease.

Results showed that ACI-24.060 elicited an anti-Abeta antibody response in the low-dose cohort. Treatment was found to be safe and well tolerated with no serious safety concerns reported.

The anti-Abeta vaccine candidate is currently being investigated at a higher dose. Initial data on amyloid plaque reduction measured by PET imaging are expected in the first half of 2024.

“By inducing a polyclonal response including antibodies against both oligomeric Abeta and pyroglutamate-Abeta, ACI-24.060 targets the same toxic species as disease modifying anti-Abeta monoclonal antibodies that slowed AD progression in phase 3 clinical trials,” said Dr Andrea Pfeifer, CEO of AC Immune SA. “As ACI-24.060, created using our SupraAntigen^® platform, specifically targets the most toxic forms of Abeta, we believe it may offer best-in-class efficacy with all the potential advantages in safety, administration and distribution that can be expected from a vaccine.”

The ABATE study will also assess the effects of ACI-24.060 in adults with Down syndrome.

The Food and Drug Administration (FDA) has granted Fast Track designation to AOC 1020 for the treatment of facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy is a rare, genetic muscle disorder caused by an abnormal expression of DUX4 (double homeobox 4) leading to skeletal muscle wasting and progressive muscle function loss. AOC 1020 is designed to reduce the expression of DUX4 mRNA and DUX4 protein in muscles. The investigational treatment consists of a monoclonal antibody that binds to the transferrin receptor 1 (TfR1) conjugated with a small interfering RNA targeting DUX4 mRNA.

The Company is currently investigating AOC 1020 in the phase 1/2 FORTITUDE study in adults with facioscapulohumeral muscular dystrophy. The double-blind, placebo-controlled study is evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AOC 1020 administered intravenously. Though the study is not powered to assess functional benefit, assessments of efficacy will be made using key biomarkers, including magnetic resonance imaging measures of muscle volume and composition. Mobility, muscle strength, patient reported outcomes, and quality of life measures will also be analyzed.

“The FDA Fast Track designation for AOC 1020 reinforces the importance of finding an effective treatment to help people living with FSHD, a devastating and debilitating muscular dystrophy disorder with no treatment options,” said Steve Hughes, MD, chief medical officer at Avidity. “AOC 1020 is designed to directly target the disease-causing gene, DUX4, to address the underlying cause of FSHD. We look forward to working collaboratively with the FDA to bring the first RNA therapy directly targeting DUX4 to patients as quickly as possible.”

Reference

Avidity Biosciences granted FDA Fast Track designation for AOC 1020 for the treatment of facioscapulohumeral muscular dystrophy. News release. Avidity Biosciences. Accessed January 18, 2023. https://www.prnewswire.com/news-releases/avidity-biosciences-granted-fda-fast-track-designation-for-aoc-1020-for-the-treatment-of-facioscapulohumeral-muscular-dystrophy-301724062.html.

Antiepileptic Drug Indications

HealthDay News — Antiepileptic drugs are associated with incident Parkinson disease, according to a study published online December 27 in JAMA Neurology.

Daniel Belete, M.B.Ch.B., from Queen Mary University of London, and colleagues investigated the association between antiepileptic drugs and incident Parkinson disease using data from 1433 individuals with a Parkinson disease diagnosis and 8598 matched controls. Routinely collected prescription data derived from primary care were used to define exposure to antiepileptic drugs (carbamazepine, lamotrigine, levetiracetam, and sodium valproate).

The researchers observed an association between antiepileptic drug prescriptions and incident Parkinson disease (odds ratio, 1.80) in a dose-response fashion, with a trend for a greater number of prescription issues and multiple antiepileptic drugs being associated with a greater risk for Parkinson disease.

“To the best of our knowledge, this is the first observational study to investigate a range of antiepileptic drugs and their association with incident Parkinson disease. As such, it sets the scene and highlights the need for further work to corroborate our findings in other large data sets because these findings could have important implications for clinical decision-making,” the authors write. “The underlying reasons for an association between antiepileptic drugs and Parkinson disease should be further explored.”

Two authors disclosed financial ties to the pharmaceutical industry.

Abstract/Full Text

HealthDay News — Antipsychotics are more often used by older adults receiving home health care (HHC) services with Alzheimer disease and related dementias (ADRD) vs those without ADRD, and their use is associated with worse functional outcomes, according to a study published online September 6 in the Journal of the American Geriatrics Society.

Jinjiao Wang, PhD, RN, from the University of Rochester in New York, and colleagues conducted a secondary analysis of 6684 adults aged 65 years and older, with and without ADRD, receiving care from an HHC agency in 2019 to examine the prevalence and predictors of antipsychotic use and its impact on outcomes among those living with ADRD. The change in the composite activities of daily living (ADL) score from HHC admission to HHC discharge (functional outcome) was measured in 5833 patients, where a positive score indicates improvement and a negative score indicates decline.

The researchers found that among patients with and without ADRD, the point prevalence of antipsychotic use was 17.2 and 6.6%, respectively. Predictors of antipsychotic use among patients living with ADRD included having greater ADL limitations, taking more medications, having behavioral and psychological symptoms, and living alone. Antipsychotic use was associated with having less ADL improvement at HHC discharge among patients living with ADRD.

“Antipsychotic use in persons with dementia is a serious patient safety issue, and it should be regularly reviewed for opportunities of deprescribing, such as dose reduction until discontinuation, whenever possible,” Wang said in a statement.

Abstract/Full Text