While those large drugmakers elbow for commercial advantage, a small biotech in the Pacific Northwest has been planning a fourth-to-market launch that could add a new competitive wrinkle.
The odds are stacked against Alder BioPharmaceuticals, a company of about 200 based in Bothell, Washington. This February, Alder filed an application for U.S. approval of its drug eptinezumab, which blocks a protein called CGRP that's also the target of the therapies from its three would-be pharma rivals.
Alder is planning for an early 2020 launch, a timeline that even if all went right would put eptinezumab more than a year behind. Its competitors are also industry-leading giants, with employees by the tens of thousands.
But Alder doesn't think it would need a large salesforce to compete, according to Robert Azelby, who joined Alder last June as its CEO. He predicted a specialty launch, tailored to a specific group of prescribers, would yield success if eptinezumab were to win approval.
"I would anticipate that Alder goes it alone in the U.S.," Azelby said in an interview with BioPharma Dive, adding Alder would consider an ex-U.S. commercial partnership.
Instead, Azelby expects a salesforce of 75 to 100 people that will focus on a small group of specialist doctors who do most of the prescribing for these migraine therapies. Per market research done by the company, roughly 3,000 doctors are writing 80% of the prescriptions for CGRP inhibitors, and 800 of those doctors account for half of all anti-CGRP prescriptions.
"We don't need armies of people going out and calling primary care because these patients are being seen by this concentrated group of physicians," said Azelby, previously an executive for Amgen and Juno Therapeutics.
That Alder thinks it can make a mark with eptinezumab speaks to the blockbuster sales expectations for the preventive migraine market overall. Sales of the three approved drugs have been modest to date, but prescription numbers suggest continued uptake of the drug class.
For better or worse, eptinezumab carries a clinical difference from the anti-CGRPs developed by Amgen, Lilly and Teva. While those three are administered subcutaneously once a month, Alder's drug is given through a quarterly IV infusion. Teva's drug, Ajovy (fremanezumab), also has quarterly subcutaneous dosing.
"There's no advantage of being an IV because patients are going to choose what they can get," Andrew Hershey, a headache medicine specialist at Cincinnati Children's Hospital said in an interview with BioPharma Dive. The migraine expert added CGRP choice has really been determined by the insurance companies, and believes the IV requirement could make it a less attractive option. Hershey has previously disclosed consulting ties to Amgen and Lilly.
Azelby, on the other hand, spins the IV requirement as a perk, requiring less frequent treatment than the other options and associated with a rapid reduction in migraine risk in the first 24 hours after infusion.
Paul Matteis, an analyst with Stifel, shares Azelby's view, arguing in a recent note to investors that payers are likely to bucket all three subcutaneous drugs together, potentially helping boost coverage of eptinezumab. Still, Matteis believes Alder's drug will command only a "meaningful minority share."
In addition to whether doctors will be convinced of eptinezumab's benefit, another question hangs over Alder.
As a regulatory decision and potential launch nears, it relates to M&A, something perhaps made more relevant given Azelby's background.
The exec was last at Juno, which was bought out by Celgene in a multi-billion dollar deal in 2018. He also sits on the board of Clovis Oncology, whose own chief executive has not been shy about his desire to be bought.
Some Wall Street analysts have wondered of a similar ending to Alder's story. Cowen & Co.'s Ken Cacciatore, for one, noted a sale would remove from Alder the burden of building a commercial presence.
"We are hopeful that Alder will be sold and therefore not have to add another salesforce and promotional effort into this category," Cacciatore wrote in February in a note to investors.
When asked directly on the company's M&A attitude, Azelby demurred, saying his Juno experience taught him to not think much about the M&A side.
"That's going to be a determinant of a third party that would like to acquire us and their engagement with the board," he said, adding his focus is on executing the launch well. "If we do those things, it's going to bring shareholder value as well as benefit to patients in either scenario, whether we stay it alone as an independent or if we are acquired."
The company has moved forward with preparations to launch by itself, naming a chief commercial officer earlier this week in Nadia Dac, previously AbbVie's vice president of global specialty commercial development.
Alder also raised $170 million in February through a public offering, adding to the $407 million in cash and equivalents it held as of Dec. 31, 2018. All told, Alder says it has enough cash to operate through the end of 2020 — accounting for the $300 million Azelby says Alder will spend this year on pre-launch preparations, such as building inventory and hiring sales representatives.
But a potential buyout could remain on investors' minds. According to a Credit Suisse investor survey from January, Alder was listed third among biotechs most likely to be acquired this year, trailing Clovis Oncology and Sarepta Therapeutics and tied with Incyte.
That said, any buyer would need to consider an intensely competitive therapeutics market that looks likely to put a ceiling on Alder's commercial prospects.
Correction: A previous version of this article misspelled Robert Azelby.