Lilly Looks To Emgality Access, Injector And Data To Differentiate Its CGRP Inhibitor

The three US FDA-approved anti-CGRP antibodies for migraine prevention have similar efficacy and matching prices, but Lilly thinks access to Emgality – including through value-based arrangements – along with the biologic's ease of use and headache-free data will differentiate the product.

Eli Lilly & Co. has hit the ground running with a carefully crafted pitch to differentiate its third-to-market CGRP inhibitor Emgality (galcanezumab-gnlm), which the US FDA has now approved in a 120 mg monthly dose for the preventative treatment of migraine in adults.

The company revealed the approval late in the evening of Sept. 27 and immediately began making its pitch to gain patient, physician and payer preference in the newly competitive migraine market in which Amgen Inc.'s and Novartis AG's Aimovig (erenumab) was the first approved CGRP inhibitor in May followed by Teva Pharmaceutical Industries Ltd.'s Ajovy (fremanezumab) on Sept. 14. Lilly believes that it will be able to provide differentiating access to Emgality, and says the therapy's ease of use and clinical trial results should make the product stand apart from its competition.

Calcitonin gene-related peptide (CGRP) inhibition is the first new mechanism of action for the prevention and treatment of migraine headaches in about two decades, but the three approved anti-CGRP products have had similar efficacy in clinical trials and their list prices are exactly the same. Lilly, like Amgen/Novartis and Teva before it, priced Emgality at $575 per month or $6,900 per year.

But with millions of patients suffering from migraine attacks who are not being effectively treated, there's a lot of room in the market for multiple new therapies.

Amgen/Novartis' Aimovig, of course, had the distinction of being the first CGRP inhibitor approved to prevent migraine headaches in the US and it's the only one of the first three approved antibodies that targets the receptor instead of CGRP itself. (Also see "Amgen's Aimovig Aims To Capture As Many Migraine Patients As Possible With $6,900 Price" - Scrip, 17 May, 2018.) However, Teva's Ajovy is the only CGRP inhibitor approved in the US for both monthly and quarterly treatment.

But while Emgality is the third CGRP inhibitor approved by the FDA, it may be the second to reach the market in Europe. (Also see "Lilly Moves Into Migraine Race With CHMP Okay" - Scrip, 24 Sep, 2018.)

US Access Lilly's First Post-Approval Priority

Lilly estimates that only about 10% of the 30 million people in the US who experience migraines are using preventative therapies, and the company's primary focus with Emgality – according to Wei-Li Shao, vice president of Lilly's Neuroscience Business Unit – is making sure as many of those patients as possible can access the product.

For starters, Lilly has developed a cost savings program through which patients covered by commercial insurance can get Emgality for free for up to 12 months, essentially eliminating co-pays required under individual health plans.

As for what where Emgality will sit on payers' formularies and what co-pay requirements will look like, those negotiations are under way.

"We've been in, for a while, discussions with every major payer in the United States to ensure access to Emgality," Shao told Scrip. "They've been receptive, so hopefully they'll be making some decisions sooner rather than later."

He explained that many payers were waiting for Emgality to be approved, so that they could make reimbursement decisions based on the FDA-approved label.

But in addition to traditional reimbursement agreements that include discounts and rebates, Shao noted that Lilly also is talking to payers about value-based arrangements (VBAs) under which health plans will pay more or less for Emgality based on outcomes for patients and the health care system.

Given what Lilly sees as a "best-in-class data package" for its drug, which reduced the number of migraine headache days enough to improve patients' daily activities in clinical trials, he said, "we'd love to do these value-based arrangements and show that [kind of improvement] within a health system and within a [health] plan."

"Going at-risk around those types of outcomes is something we're keen to do, because we believe in our product," Shao added.

Analysts are tracking CGRP inhibitor prescriptions closely, because of the competitive nature of the nascent drug class, paying close attention as Lilly and its peers negotiate reimbursement agreements for their identically priced products.

"We look forward to 1) relative prescription uptake and sales performance and 2) payer coverage decisions on the three competing drugs over the next several months," Morgan Stanley analyst David Risinger wrote in a Sept. 28 note.

"Note that since all three drugs have similar profiles, we think some major PBMs/payers may try to limit preferred formulary positions to the one or two which offer the greatest rebates/discounts," Risinger said.

Migraine Freedom, Ease Of Use As Differentiators

In addition to trying to ensure patient access, Lilly is promoting the company's clinical trial results, including the number of migraine patients whose headaches were eliminated, and the Emgality injector's ease of use as differentiating factors.

"The efficacy and clinical data really revolves around this concept of migraine freedom and the benefit of being migraine free," Shao said. "For patients that had anywhere from four migraine attacks per month up to as many as 14 attacks per month, one in seven of them had complete migraine freedom where 100% of their migraines were wiped away. That is a substantial benefit for those patients."

Also, Lilly Senior Medical Fellow Eric Pearlman noted, "about a third of patients with episodic migraine in our trials had a 75% reduction."

"These patients started with around nine headache days per month, so a 75% reduction would bring them down to about two migraine headache days per month, or one every other week as opposed to more than two a week at baseline. If you think about that over the course of year, that's giving a patient almost three months back in migraine free days," Pearlman said.

In talking to clinicians at medical conferences where Emgality data has been presented, Shao said physicians and researchers have said the possibility of achieving migraine freedom is attractive. Patients also have said in market research that they were intrigued by the chance to potentially eliminate their headaches, he added.

Pearlman noted that cutting or eliminating the number of migraine headaches patients experience improves quality of life and productivity while also reducing the use of medicines for acute treatment of headaches and cutting health care costs, including doctor office and emergency room visits.

In terms of the potentially differentiating ease of use for Emgality, the CGRP inhibitor is administered with the same injector pen that's been used to deliver multiple other Lilly drugs to more than a million patients, so the company thinks its migraine therapy will be easy to for people to self-administer.

The product will be available in retail pharmacies within weeks, but Lilly also is making Emgality available in loading dose sample kits distributed to headache specialists' and general practitioners' offices. The doctor can administer the therapy or let the patient inject themselves to demonstrate they're capable of self-administering the drug.

"Our regimen starts with a loading dose, so patients will receive two injections to start and that's a 240 mg loading dose," Pearlman said. "That gets patients to steady-state blood levels that are effective after the first dose, so within the first month as opposed to three months or six months. We see that as a real advantage to therapy, plus the ability to have that first dose in your provider's office."

Just The Beginning For Lilly's Headache/Pain Franchise

Work already is ongoing to add another indication to Emgality's label and to expand Lilly's burgeoning headache and pain franchise. Clinical trials were completed this year for Emgality in cluster headaches – sometimes referred to as suicide headaches, because of pain so severe patients have contemplated suicide to thwart the next cluster headache attack.

Results from Phase III studies in episodic and chronic cluster headaches were mixed, but Lilly is talking to the FDA about a path toward approval in the US. (Also see "Can Lilly’s Cluster Headache Data Differentiate Its CGRP Inhibitor?" - Scrip, 15 May, 2018.)

"There is clearly significant physician and patient interest in the CGRP class, but we now wait to see how the pricing dynamics play out in a market with three close competitors," Credit Suisse analyst Vamil Divan wrote in a Sept. 28 note.

Lilly also is finishing up a Phase III program in the acute treatment of migraine – on-demand therapy when a headache occurs – for lasmiditan, which Pearlman said the company intends to submit to the FDA before the end of this year. The oral drug targets 5-HT1F in the trigeminal pathway and it is designed to do so without vasoconstrictor activity seen with other migraine therapies.

While in the migraine prevention market Amgen's CGRP inhibitor has the first-mover advantage and Teva has both monthly and quarterly dosing, Divan noted that "Lilly may have the advantage of being able to supplement their efforts on Emgality with lasmiditan (for the acute treatment of migraines) once that product is approved."

Lilly, with its partner Pfizer Inc., also is developing the nerve growth factor (NGF) inhibitor tanezumab for chronic low back pain, osteoarthritis pain and cancer pain. Positive Phase III results in osteoarthritis pain were reported in July, but safety questions associated with the NGF inhibitor class have not been completely eliminated. (Also see "Pfizer/Lilly's Tanezumab Reduces Osteoarthritis Pain, But Is It Safe?" - Scrip, 18 Jul, 2018.)