dm+d

Unassigned

Lactation Safety Information

Propranolol; Metoprolol
For prophylaxis of migraine
No published evidence of safety
Low levels anticipated in milk due to the drug’s properties and likely to be degraded in infant’s GI tract, although very long half-life increases risk of accumulation in breastfed infant
Although large protein molecules may appear in colostrum, risk to preterm infants and neonates is considered to be small and unproven
22 January 2020

New Medicines

EmgalityPrevention of chronic or episodic migraine in adults

Information

Emgality
New molecular entity
Eli Lilly
Eli Lilly

Development and Regulatory status

Launched
Launched
Launched
July 2019
Jul 19Launched in the UK. Pack size 1 x single pen. Price £386.50 per single pen [19].
Mar 19Launched in Europe; countries not stated & has not yet been launched in the UK [18].
Nov 18Launched in the US [17]
Nov 18Approved in the EU [16].
Sep 18Approved in the US with a list price of $575 once-monthly, or $6,900 annually [14,15].
Sep 18Recommended for EU approval by CHMP - the full indication is "for the prophylaxis of migraine in adults who have at least 4 migraine days per month”. It is proposed that it be prescribed by physicians experienced in the treatment of migraine [13].
Dec 17Filed in US [12].
Nov 17Filed in EU via centralised procedure [11].
May 17US filing (but not EU) planned for 2017 [9].
Jan 16Lilly reports that PIII development is underway [5].
Jun 15CGRP is a potent vasodilator and is involved in neurogenic inflammation and pain signalling. It is released from neurons and acts locally on smooth muscle in blood vessels causing with the headache associated with migraine. The CGRP antibody is a humanised monoclonal antibody that selectively binds to and inhibits the activity of CGRP [1,2].

Category

Humanised monoclonal antibody that selectively binds to and inhibits the activity of calcitonin gene-related peptide (CGRP) [1,2].
Migraine affects about 6% of men and 18% of women [4]. The World Health Organization places migraine as one of the 20 most disabling illnesses. It is estimated that 13% of migraine sufferers (in the US) report using a daily preventive migraine medication [2].
Prevention of chronic or episodic migraine in adults
Subcutaneous

Further information

Yes
November 2020

Trial or other data

Jun 21Eli Lilly announce start of a PIV head-to-head study comparing galcanezumab-gnlm (120mg once-monthly with 240mg loading dose) with oral rimegepant 75mg taken every other day. The multi-site, randomised, double-blind, double-dummy, parallel-group study will include pts who meet the International Classification of Headache Disorders (ICHD) criteria for a diagnosis of episodic migraine with or without aura. The primary endpoint is 50% reduction in monthly migraine headache days and enrollment will begin later this year.[21]
Aug 19In a PIII study by Lily, galcanezumab met primary and all key secondary outcomes for efficacy and safety in patients with previous failures on two to four different standard-of-care migraine preventive medication categories. Galcanezumab cut the number of days patients experienced migraines per month by 4.1. The drug showed a 3.1-day improvement over placebo. [20]
Oct 18Four CGRP inhibitors are in development - galcanezumab, erenumab, fremanezumab (TEV-48125) and eptinezumab (ALD403). Data presented at the American Headache Society conference indicates they offer similar activity, so their developers will have to rely on factors other than their clinical profiles if and when they come to market [10].
May 18Results of EVOLVE-1 (NCT02614183) published in JAMA [13].
Jun 17Lilly presents more detail from PIII studies. In EVOLVE-1 and EVOLVE-2, a 50% reduction was seen in around 60% of patients on galcanezumab versus 36%-39% of placebo users, with all migraine attacks eliminated in 12%-15% and 6%, respectively. Similarly, the REGAIN study in chronic migraine saw the drug hit the 50% reduction threshold in around 28% of patients, compared to 15% of the placebo group [10].
May 17EVOLVE-1 & 2 and REGAIN are on-going but have all completed recruitment with completion expected Q2/3 17 [7].
May 17In the two six-month PIII trials patients with episodic migraine treated with galcanezumab (120 mg or 240 mg) experienced a greater decrease in the number of monthly migraine headache days compared to those treated with placebo. In EVOLVE-1 there was a mean reduction of 4.7 days for 120 mg and 4.6 days for 240 mg compared to an average reduction of 2.8 days for placebo, (p < 0.001, both groups). In EVOLVE-2: there was a mean reduction of 4.3 days, 4.2 days for the two doses and 2.3 days for placebo (p < 0.001). In the REGAIN study the figures were 4.8, 4.6 and 2.7 days respectively [8].
Dec 15PIII EVOLVE-2 study (NCT026141960 starts. The main purpose of this study is to evaluate the efficacy of LY2951742 in 825 adults with episodic migraine. Patients will be recruited in Argentina, Brazil, Czech Republic, Germany, Spain, UK, Israel, South Korea, Mexico, Netherlands, Taiwan & US. Collection of primary outcome data (change in number of monthly migraine headache days) is expected to complete in Jun 17 [6].
Nov 15A PIII safety study (NCT02614287) begins, & will involve 250 adults. Collection of data should be complete Sep 17 [6].
Nov 15PIII EVOLVE-1 study (NCT02614183) starts. The main purpose of this study is to evaluate the efficacy of LY2951742 in 825 participants with episodic migraine, recruited in the US & Canada. The primary outcome is change in number of monthly migraine headache days; collection of these data should complete Feb 17 [6].
Nov 15PIII REGAIN study (NCT02614261) begins. The main purpose of this study is to evaluate the efficacy of LY2951742 in 825 adults with chronic migraine. Patients will be recruited in US, Argentina, Brazil, Canada, Czech Republic, Germany, Italy, UK, Israel, Mexico, Netherlands, Taiwan & Spain. Collection of primary outcome data (change in number of monthly migraine headache days) is expected to complete in Feb 17 [6].
Jun 15LY2951742, a CGRP neutralizing antibody, for prevention of migraine met the primary endpoint in a PIIb study to prevent episodic migraine (4-14 headache days/month). The randomised, double-blind, placebo-controlled study (NCT02163993) evaluated the efficacy and safety of four doses of LY2951742 or placebo given in a once-monthly as a SC injection to 402 pts in the US with episodic migraine for 3 months. The study is objective was to assess superiority over placebo and the primary endpoint will be the mean change from baseline in the number of migraine days during the last 28-day period of the 3 month treatment phase. Eli Lilly and Company announced that LY2951742 met the primary endpoint in episodic migraine. LY2951742 demonstrated a statistically significant reduction in migraine headache days and a good safety and tolerability profile. Lilly will present data from this trial in a late-breaking session at the 57th Annual American Headache Society meeting on June 20th 2015. Full results are expected after August 2015 [1-3].

Evidence based evaluations

EmgalityChronic or episodic migraine in children and adolescents aged 6 to 17 years

Information

Emgality
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

LY2951742 is a humanised monoclonal antibody that selectively binds to and inhibits the activity of calcitonin gene-related peptide (CGRP)
Migraine is the most important cause of headache leading to a decrease in the quality of life in children and adolescents. It is more common in boys than in girls until after the menarche, when it becomes more common in girls. Chronic migraine affects 0.8-1.8% of adolescents and 0.6% of children [1].
Chronic or episodic migraine in children and adolescents aged 6 to 17 years
Subcutaneous injection

EmgalityPrevention of chronic or episodic cluster headache

Information

Emgality
Licence extension / variation
Eli Lilly
Eli Lilly

Development and Regulatory status

Not recommended for approval (Negative opinion)
Not recommended for approval (Negative opinion)
Launched
Feb 20CHMP has recommended refusal of the change to marketing authorisation (Negative opinion). The Committee considered that the results of the single study presented to support the extension did not show clearly that the medicine was effective in this indication; therefore the benefits were not considered to outweigh the risks. The company may appeal this decision and ask for a re-examination of the opinion within 15 days, but cannot present new data at this stage [13].
Jun 19Approved in US [11].
Jun 19Currently pre-registration in EU [10].
Mar 19Lilly announce US FDA acceptance of sBLA for priority review [10].
Nov 18Has been awarded breakthrough therapy status in US. Lilly plans to submit an sBLA to the FDA for Emgality for preventive treatment of episodic cluster headache in adults by the end of the year [7].
Jun 15Based on the unmet medical need and significance of this disorder, Lilly has been granted Fast Track Designation from the US FDA for cluster headache [1].
Jun 15CGRP is a potent vasodilator and is involved in neurogenic inflammation and pain signalling. It is released from neurons and acts locally on smooth muscle in blood vessels causing with the headache associated with migraine. The CGRP antibody is a humanised monoclonal antibody that selectively binds to and inhibits the activity of CGRP [1,2].

Category

LY2951742 is a humanised monoclonal antibody that selectively binds to and inhibits the activity of CGRP [1,2].
About 1 in 1,000 people suffer from cluster headache and more men than women are affected. The condition usually begins between the ages of 20 and 40 years but can start at any age [3].
Prevention of chronic or episodic cluster headache
Subcutaneous

Further information

Yes
To be confirmed

Trial or other data

Jul 19PIII RCT (NCT023974730 was terminated early due to slow recruitment (n=106 of 162 planned); however it found subcutaneous galcanezumab 300mg monthly reduced weekly frequency of attacks of episodic cluster headache across weeks 1 through 3 after initial injection vs. placebo (reduction of 8.7 vs 5.2; p=0.04) [12].
Jul 18PIII trial (NCT02397473), double blind RCT comparing drug LY2951742 (galcanezumab) to placebo for prevention of episodic cluster headache in adults completed in June 2018. Data not yet filed [8].
Nov 17Two PIII studies (NCT02438826 and NCT02397473) are still recruiting patients. Due to complete Mar 18 and Feb 18, respectively [6].
Jan 17NCT02797951 is an open-label long-term safety and tolerability study of galcanezumab administered up to once monthly in 300 participants with episodic or chronic cluster headache who have completed studies NCT02397473 or NCT02438826. The study stared Jul 16 and is due to complete Aug 20. NCT02397473 is on-going with a primary completion date of Dec 17; NCT02438826 is also on-going with a primary completion date of Jan 18 [5].
Dec 15Two ongoing PIII studies are still recruiting patients. NCT02438826 in patients with chronic cluster headaches incorporates an open-label 12 month extension period and is due to complete Dec 17; NCT02397473 in patients with episodic cluster headache is an 8-week study due to complete Aug 16 [4].
Jun 15Lilly has initiated a PIII trial programme with LY2951742 in 162 pts suffering from cluster headache. A randomised, double-blind, placebo-controlled phase III trial will investigate the efficacy of LY 2951742 or placebo (administered SC every 30 days for 12 wks) followed by a long term open-label extension phase of 12 months (NCT02438826). The trial will enrol pts in US, Belgium, Canada, Denmark, Finland, France, Germany, Italy, Spain and the UK and it will report results from August 2015 [1,2].

Evidence based evaluations