With recent phase 3 results from both Teva Pharmaceutical Industries Ltd. and Eli Lilly & Co. in the migraine space, the heat is on for more than six companies aiming to bring headache treatments to the market in the next few years.
Teva's fremanezumab had "astonishing" results from two recent phase 3 trials, said Michael Hayden, the Israeli drugmaker's chief scientific officer and president of global research and development, at the Jefferies 2017 Global Healthcare Conference on June 7. On the same day, the company shared data for the medicine against episodic migraines before presenting it in full at the American Headache Society, or AHS, annual meeting.
With this and another recent chronic migraine study in hand, Teva expects to submit a biologics license application, or BLA, with the U.S. Food and Drug Administration by the end of 2017. They will be joined by Lilly, which also expects to seek approval in the second half of the year after presenting positive data for two phase 3 drugs at the AHS meeting.
Fremanezumab is one of a cluster of drugs aiming to launch within the next few years, all promising help prevent or fight migraines for the at least 10 million Americans who are thought to be severely affected. Four of the drugs are injectables that operate by blocking calcitonin gene-related peptide, or CGRPs, to help prevent migraines both chronic — those happening more than half the days in a month — and episodic — less than half a month but still relatively frequent. One drug, Amgen Inc.'s erenumab, can boast first-mover status, as it filed its BLA on May 18.
Excluding the approval of Allergan PLC's Botox for chronic migraine in 2010, there has not been a new preventative option accessible to patients for years, said Joanna Katzman, a neurologist, director of the University of New Mexico Pain Center and president of the Academy of Integrative Pain Management.
"It decreases the stigma [around pain] completely because it is showing that this is real; these medicines are blocking a real neurochemical in your brain," Katzman told S&P Global Market Intelligence.
Teva's entry in the field has already garnered predictions of blockbuster status down the line. Barclays analyst Douglas Tsao, who projects the drug's launch for both indications sometime in the first half of 2018, estimates $50 million in sales for 2019, $170 million in 2019 and peak sales of $1 billion, the blockbuster benchmark, at some point soon after.
This is despite it not making it to market first — and possibly not even second, depending on when Lilly's galcanezumab is filed and launched.
Yet analysts point to fremanezumab's quarterly dosage system, an advantage over the monthly injections of other CGRP blockers. Evercore's Umer Raffat said in a May 31 note that efficacy of the quarterly doses is the single most important datapoint for Teva's studies.
Yet Eric Pearlman, medical lead for headaches in the U.S. medical affairs group at Eli Lilly, suggested that the significance was in removing the need for daily doses. "When you look at their current treatment options, and their lack of use, we do know that migraine patients don't like taking daily medications," he told S&P Global Market Intelligence. "So anything that decreases that interval going to be beneficial, whether it's monthly or beyond."
Alder Biopharmaceuticals Inc. is also looking to test its eptinezumab in quarterly doses, Raffat noted. Washington state-based biopharma Alder is significantly smaller than the others vying for CGRP dominance; —Teva, the next smallest, has a market capitalization 35 times larger.
Zahid Bajwa, a neurologist, director of the Boston Headache Institute and director of clinical research at Boston PainCare, speculated that it could partner with a larger company when its drug is closer to launch.
Amgen, meanwhile, recently ceded more commercial rights for its drug to Novartis AG, leading some analysts to openly wonder whether the company was not optimistic about the product. CEO Robert Bradway said in the company's first-quarter earnings call that the decision was about Novartis' neurological background and the company's desire to maximize its launch in a competitive race.
Prepping for payer talks
While Amgen is in the lead, the CGRP category is likely to be a competitive and crowded market, leaving pricing and formulary prowess as the key factors to garnering market share, Barclays' Geoff Meacham said in a June 7 note. This is particularly true as efficacy and safety seem to be largely equal among the players, he added.
"We know they will be expensive treatments," Bajwa said. Insurance companies will play a heavy role in which ones actually get to patients, he added, though he expects that all four CGRP blockers will eventually become available on payers' covered-drugs lists.
"The one first to market will probably have a little advantage, but the rest will be determined by larger data," he said, noting that long-term safety has still not been fully studied.
All said, it is unlikely that these drugs will become first options in migraine treatment or push aside existing options anytime soon, both Katzman and Bajwa said.
"I don't think this is going to be the magic bullet," Katzman said, adding that she could see using CGRP blockers in combination with Botox. Determining which blocker will actually be best for different patients will be a two- to three-year learning curve, she predicted.
Last but not least
Three oral treatments for acute migraine pain, or to diminish pain once it has already started, are also vying to make it to market in the next two to three years.
Biohaven Pharmaceutical Holding Company Ltd. a Connecticut-based company particularly focused on neurological conditions, produced positive phase 2 data for acute migraine therapy rimegepant, with phase 3 results slated for early 2018.
Rimegepant's data suggested that it is more effective against pain than Allergan's ubrogepant and less prone to side effects than Lilly's lasmiditan, Morgan Stanley's Matthew Harrison said in a May 30 note. Estimating a 2020 launch, Harrison projected $150 million in sales that year and $1.4 billion peak sales reached by 2030 — which would also make rimegepant a blockbuster drug. The company also has BHV-3500, to treat the chronic variety, in its early stages.