Therapy focus – As CGRP race hots up the only headache could be paying for them

Last week’s unveiling of positive phase III data for Eli Lilly’s CGRP drug in migraine not only came earlier than expected, but significantly heated up the race to get the first antibody for migraine onto the market.

Anti-CGRPs work by inhibiting the calcitonin gene-related peptide, which is released during migraine and cluster headaches. But in a market where triptans are largely generic and the other go-to treatment, Botox, is still going strong, the marginal efficacy that is emering from this class heralds some difficult negotiations with payers.

Targeted market

Analysts at Leerink estimate there are more than 30 million people in the US suffering from both chronic and episodic migraine. Most of these are unlikely to turn to an injected antibody treatment, but the occasional migraine sufferer is not the market Lilly, Novartis and others are targeting with CGRPs.

Instead, the groups are hoping to tap into patients who can have over 15 migraine episodes per month and whose symptoms are not controlled with currently available treatments.

Even from this reduced pool of sufferers the sales of CGRP migraine drugs are forecast to reach $3.5bn by 2022, according to consensus data from EvaluatePharma. Leading sales in what will be a highly competitive field is Amgen and Novartis with their drug erenumab, formerly known as AMG 334. The drug is expected to be filed this quarter and reach the market in 2018.

However, Lilly’s latest set of data in the Evolve 1 and Evolve 2 trials, which improved migraine-free days by between 1.8 and 2 days over placebo in episodic migraine, gives it a slight edge over the efficacy shown by erenumab in the same setting. The two-day beat over placebo in chronic migraine was broadly similar to erenumab’s results.

CGRP Trial Readouts
Project Company Migraine type Efficacy vs placebo Study Next steps
Erenumab Amgen/Novartis Episodic 1.1 days Arise (phase III) Filing Q2 2017
Episodic 1.4-1.9 days Strive (phase III)
Chronic 2.4 days Phase II study
Galcanezumab  Lilly Episodic 1.8-1.9 days Evolve-1 (phase III) Filing H2 2017
Episodic 1.9-2 days Evolve-2 (phase III)
Chronic 2 days Regain (phase III)
Eptinezumab Alder Episodic 1.0 days Phase II study Phase III Promise 1 data due Q2 17
Chronic ~2-2.8 days* Phase II study Phase III Promise 2 data due H1 2018
TEV-48125 Teva Episodic 2.6-2.8 days Phase II study
Chronic 1.7-2.0 days Phase II study
*Estimates from data presentation

This narrow advantage could be enough to help 2022 sales forecasts for the drug, which have fallen from $788m in the last 12 months to $690m, rise again. Lilly has also focused some of its research efforts on patients with a prior history of treatment failure, a setting where it believes the drug works well. This could help position galcanezumab well with physicians.

Lilly is planning on submitting galcanezumab for filing in the second half of the year, potentially putting it only four to six months behind erenumab. However, the other two competitors in the CGRP space, Teva’s TEV-48125 and Alder’s eptinezumab, are expected to come to the market in quick succession.

Top anti-CGRP Mab products by 2022e
Product Company Global Sales ($m) 2022e First Launch  Dosing
Erenumab Amgen/Novartis 1,251 Jun 2018 Monthly
TEV-48125 Teva Pharmaceutical Industries 820 Dec 2018 Monthly
Galcanezumab Eli Lilly 690 Dec 2018 Monthly
Eptinezumab Alder BioPharmaceuticals 771 Dec 2019 Quarterly
Source: EvaluatePharma

The only obvious differentiator among the four CGRP programmes is their target. Alder, Eli Lilly and Teva are developing products that hit the CGRP ligand while Amgen’s erenumab binds directly to the CGRP receptor.

So far this had made little difference – even erenumab’s short half-life of 11 days, possibly a result of it binding to the receptor, has not prevented Amgen pushing on with monthly dosing. This puts it on par with Teva’s TEV-48125 and galcanezumab, which are also dosed every four weeks.

Alder’s eptinezumab (ALD403), however, has a half-life of 26 days and is expected to be dosed quarterly, but the payoff for this duration of response is IV delivery, compared with self-administered monthly injections for the rest of the class.

Alder is working on a subcutaneous version of eptinezumab , which so far appears to have a similar dosing schedule as the IV formulation, which could give it a competitive advantage, given that the market could be driven by convenience.

Safety first

The other driver for migraine MAbs could be their tolerability and, so far, favourable safety profile – particularly for chronic patients who have failed on, or cannot tolerate, cheap generic triptans.  But even with these positive attributes CGRPs will surely be restricted to a second-line, preventative setting, as payers are likely to try step therapy programmes, using cheaper therapies first. And even if payers agree the use of CGRPs it is unlikely this will be without clamping down on costs.

This is where those coming later to market could gain market share by levering pricing. In this scenario, the first to market is likely to set a high price bar in the knowledge that the products coming behind will use reductions to gain sales. Also new entrants will inevitably allow payers to play companies off against each other.

As such, in this type of market the winners will be those that can position themselves well to doctors, patients and most importantly payers. Groups such as Lilly, who can use their experience of launching into crowded markets – diabetes, psoriasis – or those with existing relationships with neurologists – Teva and Novartis – will have a distinct advantage in shaping the future of CGRPs.

To contact the writer of this story email Lisa Urquhart in London at lisau@epvantge.com or follow @LisaEPVantage on Twitter.

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