FDA Approves sBLA for IncobotulinumtoxinA for Blepharospasm in Adults

The FDA has approved the supplemental biologics license application (sBLA) for incobotulinumtoxinA (XEOMIN, Merz) as first-line treatment for blepharospasm in adults.

The decision to approve the expanded indication was backed by data from a phase 3, randomized, placebo-controlled trial (NCT01896895) that examined the efficacy and safety of 2 different doses of incobotulinumtoxinA in patients with bilateral blepharospasm.

“Merz is proud to offer a first-line treatment option for blepharospasm, a devastating condition that has no cure and affects up to 50,000 patients in the U.S.,” Kevin O’Brien, vice president, U.S. head of neurosciences, Merz, said in a statement.¹ “This milestone, along with the July 2018 approval of XEOMIN for the treatment of chronic sialorrhea (drooling) in adults, reinforces our commitment to providing comprehensive care for patients living with movement disorders.”

The trial enrolled 61 treatment-naïve study participants, of which 55 completed the double-blind main period, who were diagnosed with blepharospasm with a baseline Jankovic Rating Scale (JRS) Severity subscore ≥2. Participants were defined as treatment-naïve if at least 12 months had passed since their last toxin treatment. Of the 55 participants that completed the main period, 39 participants entered the open-label extension period and completed the study.

Study participants were randomized 1:1:1 in a double-blind manner to single intramuscular injections of incobotulinumtoxinA 25 units (12.5 units per eye), 50 units (25 units per eye) or placebo; subjects that needed reinjection were eligible for the open-label extension period and received a second injection session of up to 70 units (35 units per eye).

The primary efficacy endpoint was the change from baseline in JRS Severity subscore determined at week 6 after injection, while secondary outcome measures included the change from baseline in blepharospasm disability index and the patient evaluation of global response at final visit.

At week 6, JRS Severity scores significantly improved from baseline with incobotulinumtoxinA 50 units versus placebo with a difference of -1.2 (P =.0004) and numerically improved with incobotulinumtoxinA 25 units versus placebo. Improvements were also reported with incobotulinumtoxinA 70 units (P <.0001).

Most of the adverse effects were of mild to moderate severity. More adverse effects were reported with incobotulinumtoxinA 50 unit (42.1%) compared to 25 unit (31.8%) or placebo (30%).² The most common adverse effects reported with use of incobotulinumtoxinA include drooping of the eyelid, dry eye, dry mouth, diarrhea, headache, vision problems, shortness of breath, respiratory infection, and nasal congestion, sore throat, and runny nose. It is not known if incobotulinumtoxinA is safe and effective in children under 18 years of age.

The FDA previously approved incobotulinumtoxinA for the treatment of blepharospasm and cervical dystonia in adults in 2010, and added indications for upper limb spasticity in adults in 2015 and chronic sialorrhea in adults in 2018.

REFERENCE

1.FDA Approves Broadened Indication for XEOMIN (IncobotulinumtoxinA) as First-Line Treatment for Blepharospasam (Involuntary Blinking) in Adult Patients [news release]. Raleigh, N.C.: Merz Americas; May 13, 2019. merzusa.com/news/fda-approves-broadened-indication-for-xeomin-incobotulinumtoxina-as-first-line-treatment-for-blepharospasm-involuntary-blinking-in-adult-patients/. Accessed May 13, 2019.

2. Mitsikostas DD, Dekundy A, Sternberg K, et al. Long-term Safety and Efficacy of IncobotulinumtoxinA for the Treatment of Blepharospasm in Botulinum Toxin-naïve Subjects: Results of a Phase III Study. Neurology. 2019;92.