With the migraine prevention space heating up, Eli Lilly and Co.'s Eric Pearlman told BioWorld Today that "having multiple options available and multiple voices trying to convey [the] message is a good thing for the patients" happy to see late-stage candidates make their ways toward market.

Indianapolis-based Lilly said galcanezumab, its antibody targeting calcitonin gene-related peptide (CGRP) for preventing episodic and chronic migraine, met its primary endpoint in three phase III trials – EVOLVE-1, EVOLVE-2 and REGAIN – showing statistically significant reductions in the number of monthly migraine headache days compared to placebo at two studied doses.

In all three experiments, the most commonly reported adverse events were injection site reactions, including pain. The observed safety and tolerability profile was consistent with findings from previous studies of galcanezumab, Lilly said, and a BLA for the compound will be submitted to the FDA in the second half of this year.

Pearlman, a medical fellow at Indianapolis-based Lilly, heads the galcanezumab program. He said the pharma giant is "right now, just really excited [about] getting to understand our own data. There's a huge unmet need."

About 38 million people in the U.S. suffer migraines, with 40 percent of those prevention-eligible, yet only 13 percent are taking a preventive medicine. The World Health Organization calls migraine the sixth most disabling condition in the world, and it's one that "has its major impact on people during the time of life when they're in peak productivity," he said. "Being able to give them back four days a month translates to a significant number of days per year."

CGRP drugs, on which work began in the late 1980s and early 1990s, represent "the first class of medicines designed specifically to prevent migraines," Pearlman noted. "All of the other migraine-preventive medications that are used were developed for other indications. The efficacy and safety/tolerability profiles [of the new therapies] bear that out." Previously, researchers explored small-molecule CGRP antagonists – telcagepant is one of them – which showed efficacy in acute treatment and was being studied in preventive treatment and had safety concerns, and so never came to the market." Kenilworth, N.J.-based Merck & Co. Inc. discontinued telcagepant in 2011.

"There's been plenty of work in the space," he said, but "it takes a while to find a targeted molecule" that's safe and effective.

In Lilly's EVOLVE-1 and EVOLVE-2, over the six-month treatment period, patients with episodic migraine treated with galcanezumab 120-mg and 240-mg doses experienced a significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo. Specifically, in EVOLVE-1, the average reduction of 4.7 days for 120 mg and 4.6 days for 240 mg compared to an average reduction of 2.8 days for placebo (p<0.001 for both dosing groups). In EVOLVE-2, the average reduction of 4.3 days for 120 mg and 4.2 days for 240 mg compared to an average reduction of 2.3 days for placebo (p<0.001 for both dosing groups). Patients treated with galcanezumab turned up statistically significant improvement compared to placebo on several pre-specified secondary endpoints, including response rates and measures of daily activities.

Over the three-month REGAIN treatment period, patients with chronic migraine treated with galcanezumab 120-mg and 240-mg doses experienced a significantly greater decrease in the average number of monthly migraine headache days compared to patients treated with placebo (average reduction of 4.8 days for 120 mg and 4.6 days for 240 mg compared to an average reduction of 2.7 days for placebo; p<0.001 for both dosing groups).

More data from all three trials will roll out later at scientific meetings, Pearlman said. Full data could be presented at a medical meeting as early as the American Headache Society meeting in Boston in June, speculated Leerink analyst Seamus Fernandez.

Others in the CGRP migraine prevention space include Thousand Oaks, Calif.-based Amgen Inc. (partnered with Basel, Switzerland-based Novartis AG) with erenumab (AMG-334), which has shown positive phase III data in two trials; Alder Biopharmaceuticals Inc., of Bothell, Wash., with eptinezumab in phase III and results expected this quarter; and Petah Tikva, Israel-based Teva Pharmaceuticals Ltd., with TEV-48125 undergoing phase IIb trials.

An intellectual property dispute between Teva and Lilly/Alder is "coming to a head" in the EU, said Fernandez in a research report. "We believe settlement involving a royalty payment to Teva is a possibility." The Israeli firm "owns patents with the earliest priority of invention date around compositions binding broadly to CGRP ligand (vs. Lilly and Alder)," he wrote. "Teva's patent claims have survived the first round of the EU patent opposition process, but the decision could be reversed upon appeal. In our view, a mid-single-digit royalty on EU sales from Lilly and Alder to Teva seems the most likely scenario. Questions around the breadth of the patent claims by Teva remain and [the issue] is something Lilly highlighted to us. On balance, we believe galcanezumab is likely to get to market before Teva, limiting the risk that a launch is blocked."