Ubrogepant, erenumab, fremanezumab, and galcanezumab are monoclonal antibodies that target CGRP for the treatment of migraines. Ubrogepant is approved for acute treatment while the others are approved for prevention. Clinical trials showed they significantly reduced monthly migraine days compared to placebo. Common side effects include pain or redness at the injection site. They were approved by the FDA between 2018-2019 and cost approximately $6,000-7,000 per year.

1. Recent Advances In Migraine
Management
Dr.Satyabrata Sahoo
Pdt 1st Yr
Clinical And Experimental Pharmacology
School Of Tropical Medicine ,Kolkata

2. Ubrogepant
 MOA- Block CGRP a protein thought to play a
role in pain transmission.
FDA approved for migraine without a black
box warning.
The most common side effects are nausea,
tiredness and dry mouth.

4.  In ACHIEVE I, Ubrogepant was administered to treat a single
migraine attack in comparison with placebo (n = 456) at doses
of 50 mg (n = 423) and 100 mg (n = 448) in 1327 patients.
 The study met its primary end points, with both doses
showing a larger, statistically significant percentage of patients
achieving pain freedom at 2 hours after the initial dose
compared to placebo.
 In ACHIEVE II, the therapy was examined in 1686 patients
randomized 1:1:1 to 25-mg (n = 435) or 50-mg (n = 464)
ubrogepant, or placebo (n = 456).
• In December 2019, the U.S. Food and Drug
Administration approved Ubrogepant produced by Allergan
USA, Inc. for treatment of migraine after onset.

7. Erenumab
Erenumab is a medication which targets
the CGRPR for the prevention of migraine.
It was the first of the group of CGRPR
antagonists to be FDA approved in 2018.
It is a form of monoclonal antibody therapy in
which antibodies are used to block
the receptors for the protein CGRP.
It is administered by subcutaneous injection of
70 or 140 mg once a month.

8. In the phase III STRIVE clinical trial 955 patients
were divided into three groups in a 1:1:1 ratio.
Each group was injected subcutaneously monthly
with 0, 70 or 140 mg erenumab over a period of 6
months. The results were measured as mean
monthly migraine days in months 4, 5, and 6.
Approval and marketing
The United States Food and Drug
Administration approved the medication for the
preventive treatment of migraine in adults on
May 17, 2018. The list price was reported to
be US$6,900 per year.

9. Fremanezumab
• Fremanezumab is a fully humanized monoclonal antibody directed
against calcitonin gene-related peptides (CGRP) alpha and beta. The
precise mechanism of action is unknown.
• It is the only approved anti-CGRP monoclonal antibody that can be
given with a quarterly interval to prevent migraine.
• It is given by injection under the skin.
• The most common side effect is pain and redness at the site of
injection.
• It was approved for medical use in the United States in 2018.
• The wholesale cost in the United States as of 2019 is $US 369.90
per month.

10. • It is degraded by proteolysis to
small peptides and amino acids, which are reused
or excreted via the kidney.
• Fremanezumab was discovered and developed
by Rinat Neuroscience, was acquired by Pfizer in
2006, and was then licensed to Teva.
• It was approved by the US Food and Drug
Administration in September 2018.In April 2019,
fremanezumab was approved for marketing and
use in the European Union.

11. Galcanezumab
• Galcanezumab is a humanized monoclonal
antibody used for the prevention of migraine. It is also
used for cluster headaches.
• Common side effects include pain or redness at the site
of injection. Other side effects may
include hypersensitivity reactions.
• It is directed against calcitonin-related
polypeptides alpha and beta.
• This drug was developed by Eli Lilly. It was approved for
medical use in the United States in 2018.
• Costs about 7,000 USD per year in the United States as
of 2019.

12. • In September 2018, galcanezumab was
approved in the United States for the
preventive treatment of migraine in adults.
• The U.S. Food and Drug administration (FDA)
approved galcanezumab based on evidence
from three clinical trials :Trial 1/NCT02614183,
Trial 2/NCT02614196, and Trial
3/NCT02614261.

13. • Trial three enrolled patients with a history of
chronic migraine headaches. Patients were
assigned to receive galcanezumab or placebo
injection once a month for three months.
• The benefit of galcanezumab was assessed based
on the change from baseline in the number of
migraine days per month during the three-month
treatment period, comparing the galcanezumab
and placebo groups.
• In June 2019, galcanezumab was approved in the
United States for the treatment of episodic
cluster headache in adults.

14. Management of Migraine
Drugs for acute attack: Paracetamol or NSAIDs
If not controlled Triptans(or ergotamine+caffeine) If not
controlled Opiods or Droperidol(If opioid tolerant patiets)
If not controlled Propofol.
Drugs for prophylaxis:
• Beta blockers like propranolol,timolol,nadolol.
• CCBs like Flunarizine,diltiazem,verapamil,nimodipine
• TCAs like amitryptiline,imipramine,nortryptiline
• Antiepileptics like topiramate,valproate,gabapentin
• Methysergide,cyproheptadine,clonidine,candesartan,Botulinu
m toxin A.

15. References
1. Allergan Announces FDA Acceptance of New Drug Application for Ubrogepant for the Acute
Treatment of Migraine [press release]. Dublin, Ireland: Allergan. Published March 11, 2019.
allergan.com/news/news/thomson-reuters/allergan-announces-fda-acceptance-of-new-drug-
appl. Accessed March 11, 2019.
2.Tepper S, Ashina M, Reuter U, et al. Safety and efficacy of erenumab for preventive
treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2
trial. Lancet Neurol 2017;16:425–434.
3.Dodick, David W.; Silberstein, Stephen D.; Bigal, Marcelo E.; Yeung, Paul P.; Goadsby, Peter J.;
Blankenbiller, Tricia; Grozinski-Wolff, Melissa; Yang, Ronghua; Ma, Yuju; Aycardi, Ernesto (15
May 2018). "Effect of Fremanezumab Compared With Placebo for Prevention of Episodic
Migraine". JAMA. 319 (19): 1999.
4.FDA approves first treatment for episodic cluster headache that reduces the frequency of
attacks [press release]. Silver Spring, MD: FDA. Published June 4, 2019. fda.gov/news-
events/press-announcements/fda-approves-first-treatment-episodic-cluster-headache-
reduces-frequency-attacks. Accessed June 4, 2019.