Approval of First Therapy to Counteract Muscle Loss in Spinal Muscular Atrophy

Introduction

The FDA has granted approval for apitegromab (Isembyld) injection, designed to treat spinal muscular atrophy (SMA) in both adults and pediatric patients aged 2 years and older who are currently receiving treatment targeting the SMN2 gene. This announcement was made by the agency recently.

This drug marks the first therapy approved specifically for SMA that directly addresses muscle loss.

Understanding SMA

Spinal muscular atrophy is a serious genetic condition affecting approximately one in 10,000 live births and is recognized as a leading genetic cause of infant mortality. It arises from reduced levels of the SMN protein, which is crucial for motor neuron health, due to deletions or mutations in the SMN1 gene. Another gene, SMN2, produces lower levels of functional SMN protein, which is insufficient for motor neuron maintenance.

Several existing treatments, like risdiplam (Evrysdi) and nusinersen (Spinraza), aim to enhance SMN protein production by correcting the underlying genetic defect.

Need for New Therapies

Although these available treatments have significantly improved outcomes for many patients, those with advanced SMA frequently face considerable motor limitations, underscoring the need for therapies that directly mitigate muscle loss.

Clinical Trials and Results

Apitegromab’s safety and efficacy have been evaluated in the SAPPHIRE trial, a 52-week double-blind, phase III study. This trial involved participants aged 2 to 21 who had non-ambulatory type 2 or type 3 SMA with documented genetic evidence, motor function scores of 10 to 45 on the Hammersmith Functional Motor Scale-Expanded, and a history of treatment with nusinersen or risdiplam.

Patients were randomized to receive apitegromab at doses of 10 mg/kg or 20 mg/kg, or a placebo, administered once every four weeks for about one year. The analysis revealed that participants receiving 10 mg/kg of apitegromab showed improvements in motor function, while those on placebo declined. The treatment group was more than twice as likely as the placebo group to show a clinically meaningful improvement (34.2% vs 13.5%).

Adverse Reactions

The incidence and severity of adverse events were comparable between the apitegromab and placebo groups, with common reactions including upper respiratory infections, vomiting, cough, and headache. It is important to note that patients treated with apitegromab experienced an increased risk of fractures, some of which were serious. Additionally, the FDA has cautioned that the drug may cause fetal harm and could affect reproductive function.

Supportive findings have also emerged from the phase II TOPAZ trial regarding apitegromab.

Dosing Information

The recommended dosage of apitegromab is 10 mg/kg, administered as an intravenous infusion every four weeks, lasting approximately 60 to 120 minutes, with an infusion rate no greater than 150 mL/hour. The drugmaker has announced that apitegromab will be shipped in the coming days.

Disclaimer: This content is for informational purposes only and does not substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.

Fuente: https://www.medpagetoday.com/neurology/generalneurology/122994