Differences in CGRP Inhibitors

With the approval of fremanezumab and emgality in September, the FDA has approved three CGRP inhibitors. All three drugs are administered by subcutaneous (subQ) injection, but differ in their dosage forms and injection frequency. 

Generic Name	Brand Name	Company	Dose	Dosage Form	Approval Date
Erenumab	Aimovig	Amgen, Novartis	70 or 140 mg* subQ monthly	70 mg auto-injector and ​70 mg pre-filled syringe	5/17/18
Fremanezumab	Ajovy	Teva	225 mg subQ monthly or 675 mg ** subQ every 3 months	225 mg pre-filled syringe	9/14/18
Galcanezumab	Emgality	Lilly	240 mg *** subQ initial dose, ​then 120 mg subQ monthly	120 mg auto-injector and ​120 mg pre-filled syringe	9/27/18

* 140 mg is administered as 2 consecutive 70 mg subQ injections
** Given as 3 consecutive 225 mg subQ injections
*** 240 mg is administered as 2 consecutive 70 mg subQ injections

Erenumab and galcanezumab are administered monthly and available as either an auto-injector or prefilled syringe. Fremanezumab can be given monthly or quarterly. Because the drug is more viscous, it is currently only available as a prefilled syringe, but Teva is working on an auto-injector. All three drugs are only available in a single strength. A higher dose (erenumab and fremanezumab), therefore require multiple injections.

All three drugs are well tolerated. The most common adverse effect with all three drugs is injection site reactions. Erenumab also lists constipation as a common adverse effect.

The Wholesale Acquisition Cost (WAC) for one syringe is $575 for all three drugs ($1,725 per quarterly dose of femanezumab) for an annual WAC of $6,900. Each company is also offering a program to cover the copay for patients with commercial insurance.

Express Scripts is pushing CGRP inhibitor manufacturers to set a lower price for their drug, rather than set a high price and offer a rebate. Express Scripts also wants to set up performance contract for the drugs based on efficacy on use of the drug in their patients. 

ICER released a final review of CGRP inhibitors on July 3, 2018. ICER found insufficient evidence to recommend erenumab or fremanezumab over oral preventative drugs or botulism toxin for prevention of migraine in untreated patients. ICER did find evidence of a benefit for use of erenumab or fremanezumab in patients that had previously failed preventative therapy for chronic migraine. Data was supportive  but inconclusive for prevention of episodic migraine. ICER found insufficient evidence for use of galcabezumab in either indication. The drugs were found to be safe with the most common ADR of injection site reactions and upper respiratory symptoms. CGRP inhibitors were estimated to improve quality of life years (QALY) for episodic and chronic migraine patients. With an announced WAC price of $6,900/year for erenumab, ICER estimates an annual cost of $5,000/year after discounts. ICER estimates a price of $3,700 to $5,300 per year to be cost effective. Erenumab or fremanezumab were found to be cost effective in QALY gained in patients that had failed at least one preventative therapy. The estimated cost per QALY were lower for chronic migraine compared to episodic migraine. ICER felt that insurers would be justified in setting limits or restrictions on CGRP inhibitors due to insufficient long-term safety data and high cost. 

With pricing equivalent month the three drugs, we can expect to see more aggressive marketing and pricing as they battle for market share. There are currently no comparative trials between the three new drugs or comparing an CGRP-inhibitor to older oral drugs.