The FDA Approved a New Oral, As-Needed Tablet for Acute Migraine Treatment

The Food and Drug Administration (FDA) has approved Symbravo (meloxicam and rizatriptan; Axsome Therapeutics, New York, NY) for the acute treatment of adults diagnosed with migraine with or without aura. Symbravo, previously known as AXS-07, is a single-dose, oral medication for use as-needed. Axsome Therapeutics announced that it expects Symbravo to become commercially available in the United States in approximately 4 months.

Symbravo is composed of rizatriptan, a 5-HT1B/1D agonist, and meloxicam, COX-2, a preferential nonsteroidal anti-inflammatory drug (NSAID). Symbravo was developed using the Molecular Solubility Enhanced Inclusion Complex (MoSEIC) technology, which enables rapid absorption of the meloxicam component of Symbravo without impacting its extended plasma half-life.

Symbravo’s approval was based on positive data from the MOMENTUM (NCT03896009), INTERCEPT (NCT04163185), and MOVEMENT (NCT04068051) phase 3 clinical trials, which evaluated the safety and efficacy of the medication for the acute treatment of people with migraine with and without aura. In INTERCEPT, 302 participants were randomized to receive, at the earliest onset of migraine, either Symbravo (n=152) or placebo (n=150). The study’s coprimary endpoints were the percentage of participants reporting headache pain freedom and absence of most bothersome symptoms (defined at migraine onset) at 2 hours after treatment.

Compared with placebo:

• More people who received Symbravo experienced headache pain freedom (32.6% vs 16.3%; P=.002) at hour 2.
• More people who received Symbravo experienced absence most bothersome symptoms (43.9% vs 26.7%; P=.003) at hour 2.
• More people who received Symbravo experienced freedom of pain progression (73.5% vs 47.4%; P<.001) between 2 and 24 hours after treatment.
• Within 24 hours of treatment, rescue medication was not required for 85% of individuals who received Symbravo.

The MOMENTUM study included 1594 participants with migraine with or without aura who experienced inadequate response after using other acute treatments. Participants were randomized 2:2:2:1 to receive either Symbravo, rizatriptan 10 mg, meloxicam 20 mg, or placebo. MOMENTUM had the same coprimary endpoints as INTERCEPT.

• Compared with placebo, more people who received Symbravo experienced headache pain freedom (19.9% vs 6.7%; P<.001) at hour 2.
• Compared with placebo, more people who received Symbravo experienced absence of most bothersome symptoms (36.6% vs 24.4%; P=.002) at hour 2.
• Symbravo was shown to be significantly superior for achieving sustained pain freedom from 2 to 24 hours after treatment as compared with rizatriptan alone.
• Within 24 hours of treatment, rescue medication was not required for 77% of individuals who received Symbravo.

The MOVEMENT study included 706 individuals who previously participated in the MOMENTUM or INTERCEPT clinical trials. All participants received Symbravo for acute treatment of migraine, with a primary endpoint of long-term safety up to 12 months.

• 293 participants experienced treatment-emergent adverse events (TEAEs), with 8 serious TEAEs
• 118 participants had suspected drug-related TEAEs.
• 10 participants stopped taking Symbravo due to TEAEs.
• 13 participants withdrew from the study due to TEAEs.

“Results of multiple clinical trials demonstrate that SYMBRAVO can provide rapid and long-lasting freedom from migraine pain, whether treatment is taken early in the attack while the pain is mild, or later in the attack when the pain may be severe,” said Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Cetner of the Albert Einstein College of Medicine. “The approval of SYMBRAVO is a long awaited and much welcomed advancement for clinicians and our patients, providing a new, meaningful treatment option.”

Across the INTERCEPT, MOMENTUM, and MOVEMENT studies, dizziness and somnolence were the most common reported adverse events. Symbravo’s label contains a Boxed Warning for risk of serious cardiovascular and gastrointestinal events.