Physician Views: Do prescribers hold high hopes for Eli Lilly's one-two strategy in migraine treatment and prevention?

Last week, Eli Lilly announced positive Phase III data (across three trials) for its CGRP inhibitor galcanezumab for the prevention of episodic and chronic migraines. The results, which Eli Lilly will use to support a regulatory filing with the FDA later this year, appear broadly comparable with previously published Phase III and Phase II data for other drugs in the CGRP class; of which there are three in late-stage development – Amgen and Novartis' erenumab, Teva's TEV-48125 and Alder Biopharmaceuticals' eptinezumab. 

With the market for CGRP inhibitors widely forecast to support peak revenues of more than $5 billion – and some bullish projections suggesting it could be worth twice this amount – analysts and investors are keen to identify how each of these candidates can be differentiated. Eli Lilly's strategy, it would appear, is based largely around development of a broader migraine portfolio designed to comprise at least two products, where galcanezumab will be flanked by lasmiditan, a serotonin 1F agonist recently integrated into the company's late-stage pipeline through the billion-dollar acquisition of CoLucid Pharmaceuticals (technically lasmiditan has been re-integrated into Eli Lilly, whose scientists initially discovered and developed the compound before out-licensing it to CoLucid in 2005).

Prior to this acquisition, CoLucid announced positive data from the first of two Phase III trials last year, with results from the second study expected by the end of 2017. Importantly, lasmiditan does not cause vasoconstriction in the rabbit saphenous vein, a surrogate assay that predicts vasoconstriction in human coronary arteries. This means that in contrast to triptans, lasmiditan would not be contraindicated for use with medications that cause blood vessel constriction, a potentially important differentiating feature with cardiovascular risk patients estimated to account for up to 30 percent of the acute migraine population. In addition, lasmiditan could offer an alternative therapeutic option for patients who do not respond to triptans, although some KOLs have questioned its side-effect profile regarding, in particular, onset of dizziness. Although Phase III data demonstrates a more manageable side-effect profile, Phase II results showed a higher prevalence of adverse events.

To get a better understanding of how both galcanezumab and lasmiditan are viewed by potential prescribers based on currently available data, we are snap-polling US and EU5-based neurologists and primary care physicians with the following questions…

Eli Lilly has reported new Phase III results for its CGRP inhibitor galcanezumab in patients with both episodic and chronic migraine.

Patients enrolled in the EVOLVE-1 and EVOLVE-2 trials (episodic migraine) had an average of 9.1 migraine headache days per month at baseline. Over the six-month treatment period, patients treated with galcanezumab in EVOLVE-1 experienced average reductions of 4.7 monthly migraine days (120mg dose) and 4.6 monthly migraine days (240mg) versus an average 2.8 day reduction for placebo. In EVOLVE-2, patients treated with galcanezumab experienced average reductions of 4.3 monthly migraine days (120mg) and 4.2 monthly migraine days (240mg) versus an average 2.3 days reduction for placebo.

How clinically meaningful do you consider these results?

Not meaningful

Slightly meaningful

Moderately meaningful

Very meaningful

Extremely meaningful

Patients enrolled in the REGAIN trial (chronic migraine) had an average of 19.4 migraine headache days per month at baseline. Over the three-month treatment period, patients treated with galcanezumab experienced average reductions of 4.8 monthly migraine headache days (120mg) and 4.6 monthly migraine headache days (240mg) versus an average 2.7 day reduction for placebo.

How clinically meaningful do you consider these results?

Not meaningful

Slightly meaningful

Moderately meaningful

Very meaningful

Extremely meaningful

Assuming a number of CGRP inhibitors – such as the aforementioned galcanezumab – come to market with similar clinical profiles (in terms of efficacy and safety – safety to date has been largely clean) and excluding pricing/access considerations, which of the following strikes you as the factor most likely to prompt you to favour prescribing one particular product in favour of the others…

It is marketed by a company which has experience in the neuroscience market/a company I know well

It is well endorsed by key opinion leaders

It has the best medical affairs support

It has high profile clinical data (i.e. in terms of journal publication/conference presentation)

It has first-to-market status

It is self-injected once every three months (versus self-injection once or twice a month like the others)

It is intravenously administered (by a healthcare professional) every three months

It is intravenously administered (by a healthcare professional) every six months

Looking at the acute treatment of migraine in adults, initial Phase III data for lasmiditan shows that after two hours, 28.2% of patients treated with the 100mg dose and 32.2% of patients treated with the 200mg dose were migraine headache pain free at two hours versus 15.3% of patients in the placebo group. In addition, 40.9% of 100mg dose patients and 40.7% of 200mg dose patients were free from the most bothersome associated symptom of migraine (nausea, phonophobia or photophobia) two hours after dosing, versus 29.5% of patients in the placebo group.

Unlike treatment with triptans, lasmiditan would not be contraindicated from use with medications that cause blood vessel constriction. Taking this into account, its potential use in patients who don't respond to triptan therapy and the key data points above, how compelling do you perceive the commercial opportunity for lasmiditan to be?

Not compelling

Slightly compelling

Moderately compelling

Very compelling

Extremely compelling

Dizziness appears to be the most frequent side effect associated with lasmiditan. In the Phase III SAMURI trial, dizziness was reported as an adverse event in 11.9% of patients receiving the 100mg dose and 15.4% of patients the 200mg dose, versus 3.1% of patients in the placebo group. In an earlier Phase II trial, dizziness was reported in 23.2% of lasmiditan patients receiving a 50mg dose, 25.6% a 100mg dose, 38% a 200mg dose and 37.1% a 400mg dose of lasmiditan, compared to no patients in the placebo arm.

Assuming a second Phase III trial demonstrates a similar rate of dizziness to SAMURI (which is somewhat lower than the Phase II trial), how would you interpret these data and how would this impact your initial utilisation of lasmiditan.

I would base utilisation exclusively on Phase III data – no utilisation of lasmiditan

I would base utilisation exclusively on Phase III data – minimal utilisation of lasmiditan

I would base utilisation exclusively on Phase III data – moderate utilisation of lasmiditan

I would base utilisation exclusively on Phase III data – significant utilisation of lasmiditan

I would base utilisation exclusively on Phase III data – very significant utilisation of lasmiditan

I would base utilisation on Phase II/III data – no utilisation of lasmiditan

I would base utilisation on Phase II/III data – minimal utilisation of lasmiditan

I would base utilisation on Phase II/III data – moderate utilisation of lasmiditan

I would base utilisation on Phase II/III data – significant utilisation of lasmiditan

I would base utilisation on Phase II/III data – very significant utilisation of lasmiditan

Results and related analysis will shortly be published for FirstWord Pharma PLUS subscribers to read, with the opportunity for non-FirstWord Pharma PLUS subscribers to purchase these findings. To be notified when poll results and analysis become available, please click here.

As always, FirstWord would very much like to receive your feedback and suggestions. Note: FirstWord Polls are powered by MedePolls, a fast-turnaround service to conduct instant polls of up to five questions with guaranteed samples that include physicians from dozens of specialties and over 100 markets. To conduct this poll with a different audience, or an entirely different poll, contact us at info@firstwordpharma.com

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