AEON Biopharma Reports Disappointing Interim Phase 2 Results of Migraine Preventive ABP-450
ABP-450, a botulinum toxin type A complex agent, failed to meet either primary or secondary end points in a cohort of 325 patients with chronic migraine.
Marc Forth
Newly announced preliminary top-line results from a planned interim analysis of a phase 2 study (NCT04845178) showed that treatment with ABP-450 (AEON Biopharma) did not meet its primary end point, failing to distinguish itself from placebo in reducing monthly migraine days (MMD).1
Between weeks 13 and 24, those randomly assigned to either ABP-450 150 U or 195 U had a reduction of 8.5 and 7.7 MMDs, respectively, compared with a reduction of 8.4 days in the placebo arm. The data, which compiled 325 patients with chronic migraine, showed no statistically significant differences between active and placebo arms (150 U arm: P = .9132; 195 U arm: P = .3611).
"While we were surprised and disappointed that ABP-450 did not demonstrate statistically significant superiority over placebo in this interim readout, both active arms showed a reduction in monthly migraine days directly in-line with our expectations,” Marc Forth, president and chief executive officer at AEON, said in a statement.1 "We are conducting additional analyses of the interim data to understand the highly abnormal and unexpected placebo effect and further evaluate the results of this study to determine the best path forward in the development of ABP-450 for the preventive treatment of migraine."
None of the secondary outcome measures, which included percentage of patients with reduction in MMDs, mean change in Migraine-Specific-Quality of Life domains, and reductions in Migraine Physical Function Impact Diary, among others, were also not significant. The company did note though that reduction in MMDs observed in the placebo group was reportedly “much higher” than expected based on previous studies.
ABP-450, or prabotulinumtoxinA injection, is a 900-kDA botulinum toxin type A complex with proven safety profile. When injected at therapeutic doses, the agent works by blocking the release of acetylcholine, a neurotransmitter that signals muscles to contract. The thought behind ABP-450 is to reduce nerve and muscle activity in strategic areas, ultimately alleviating the symptoms of migraine, cervical dystonia, and other neuromuscular disorders.
The phase 2 trial featured adults with chronic migraine who have had at least a 1-year history of their condition and on average, at least 6 migraine or probable migraine days per month. Patients with chronic tension-type headache, new persistent daily headache, trigeminal autonomic cephalgia, or cranial neuropathy, are excluded. Individuals with a diagnosis of myasthenia gravis, Lambert-Eaton syndrome, amyotrophic lateral sclerosis, or any other significant neuromuscular disease that might interfere with the study, are also excluded.
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In October 2023, AEON announced topline results for the episodic migraine cohort of the phase 2 study, a group of 305 patients who also received either high or low-dose ABP-450, or placebo. On the primary end point, results showed that treatment with ABP-450 resulted in MMD reductions of 4.8 and 5.0 days in the 150 U and 195 U dose groups, respectively, compared with 4.2 days for those on placebo, during weeks 21-24. The therapy demonstrated a favorable safety profile; however, it effects on the primary end point ultimately did not meet statistical significance.
In the episodic migraine cohort, 69% of patients in the ABP-450 195 U dose group achieved at least a 50% reduction in MMD, which was statistically significant compared with the 52% observed on placebo (P = .0132). In addition, 37% and 34% of those in the 195 U and 150 U groups, respectively, had at least a 75% reduction, compared with 23% of those on placebo (P = .0245; and P = .0439). Using the Patient Global Impression of Severity scale, results showed statistically significant improvements of –0.9 in the 150 U group and –1.0 in the 195 U group, relative to –0.6 for placebo (P = .0436; and P = .0028).
Following the release of the results for the episodic cohort, the company noted it plans to request an end-of-phase 2 meeting with the FDA to discuss the protocol and study design for a phase 3 trial. At the time, Froth said in a statement that “We believe these robust topline data announced today from the Phase 2 trial fulfill our objectives for this study and support the decision to advance the program into a larger pivotal study."
