Breaking News
January 17, 2018 - Top nutrients needed to boost mood and energy levels on Blue Monday
January 17, 2018 - Scientists develop unique technique to map elasticity of cell components
January 17, 2018 - Obesity surgery reduces the risk of death by half finds new study
January 17, 2018 - Raw Meat Not the Safest Choice for Your Dog or for You
January 17, 2018 - High-Dose Aspirin Preferred for Kawasaki’s
January 17, 2018 - Study suggests risk management approach to combat EMS fatigue
January 17, 2018 - A new therapy against obesity
January 17, 2018 - Doctors warn against holding your nose and closing your mouth to contain a sneeze
January 17, 2018 - Measles outbreak alarms public health officials
January 17, 2018 - FDA Slaps Class Warning on Gadolinium Contrast Agents
January 17, 2018 - Distinct human mutations can alter the effect of medicine
January 17, 2018 - ASIT biotech’s new article presents clinical results of gp
January 17, 2018 - Alternative tobacco use by adolescents associated with greater odds of future cigarette smoking
January 17, 2018 - A High-Salt Diet Produces Dementia In Mice
January 17, 2018 - Scientists provide insights into crucial interaction for DNA repair
January 17, 2018 - Sanofi and Regeneron Announce Positive Topline Pivotal Results for PD-1 Antibody Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma
January 17, 2018 - Morning Break: Pfizer Kills AD/PD Pipeline; Trump Affirms His Mental Health; Humira Pricing Strategy
January 17, 2018 - Researchers see gene influencing performance of sleep-deprived people
January 17, 2018 - Fast food triggers the immune system making it hyperactive
January 17, 2018 - Scientists find increased risk of HIV outbreaks in Ukraine due to war-related migration
January 17, 2018 - New universal flu vaccine moves to clinical trial phase and could be a reality soon
January 17, 2018 - Cocaine de-addiction breakthrough shows promise
January 17, 2018 - FDA Accepts New Drug Application for Seysara (sarecycline) for the Treatment of Moderate to Severe Acne
January 17, 2018 - Robotic Telestenting; BP Cuff Smartwatch; Medicare Bundled Care
January 17, 2018 - New cellular approach found to control progression of chronic kidney disease
January 17, 2018 - Lamprey genes provide clues to repair spinal cord damage, finds study
January 17, 2018 - Tissue-based soft robot could lead to advances in bio-inspired robotics
January 17, 2018 - Mostly the healthy and wealthy Americans use mobile phone apps to track sleep habits
January 17, 2018 - FDA Alert: Varubi (rolapitant) Injectable Emulsion: Health Care Provider Letter
January 16, 2018 - NeuroBreak: Rough Days for Neuroscience Research; Another Migraine Drug Advances
January 16, 2018 - The ‘greatest pandemic in history’ was 100 years ago – but many of us still get the basic facts wrong
January 16, 2018 - Serena Williams Shares Childbirth Ordeal
January 16, 2018 - The Artificial Brain as Doctor
January 16, 2018 - Type 2 diabetes has hepatic origins
January 16, 2018 - Expert discusses how to identify, support individuals with drug or alcohol addiction in workplace
January 16, 2018 - Starting menstruation early increases risk of cardiovascular disease and stroke in later life
January 16, 2018 - CapsoVision receives CE Mark approval for use of CapsoCam Plus System in pediatric patients
January 16, 2018 - Researchers develop new dynamic statistical model to follow gene expressions over time
January 16, 2018 - Alzheimer’s ‘looks like me, it looks like you’
January 16, 2018 - By the Numbers: Physicians’ Economic Impact
January 16, 2018 - Sound Health | NIH News in Health
January 16, 2018 - Modifying baby formula doesn’t prevent type 1 diabetes in children
January 16, 2018 - Energy drinks dangerous for kids
January 16, 2018 - When you need a breast screening, should you get a 3-D mammogram?
January 16, 2018 - Johns Hopkins gets approval to perform HIV positive to HIV positive living donor kidney transplants
January 16, 2018 - The Salk Institute and Indivumed collaborate for cutting-edge cancer research
January 16, 2018 - Study reveals negative long-term effects of heavy cannabis use on brain function and behavior
January 16, 2018 - Many gym-goers injure themselves by pushing harder to be better than friends
January 16, 2018 - Risankizumab Meets All Primary Endpoints Reporting Positive Results in Fourth Pivotal Phase 3 Psoriasis Study
January 16, 2018 - Federal Junk Food Tax Feasible, Study Says
January 16, 2018 - Do girls have stronger teeth than boys?
January 16, 2018 - New high-sensitivity blood tests could aid faster diagnosis and treatment for heart attack
January 16, 2018 - How fatal mitochondrial diseases may strike offspring of families with no history of the conditions
January 16, 2018 - TherapeuticsMD Announces FDA Acceptance of New Drug Application and Prescription Drug User Fee Act (PDUFA) Date for TX-004HR
January 16, 2018 - Morning Break: Food Pharmacies; Obamacare Sign-ups Dip; Top Pot Studies
January 16, 2018 - Blood pressure declines 14 to 18 years before death
January 16, 2018 - ViLim Ball technology helps reduce uncontrollable shaking hands
January 16, 2018 - Researchers use immune-mimicking biomaterial scaffolds to fast track T cell therapies
January 16, 2018 - In Wisconsin, hopes rise for production of a lifesaving radioactive isotope
January 16, 2018 - Researchers develop software to better predict risk of leakage around aortic stents
January 16, 2018 - Bile acids could directly burn away lipids in the fat depots
January 16, 2018 - Cycling does not negatively impact sexual and urinary health finds study
January 16, 2018 - Severe peer victimization in childhood may contribute to mental health issues in adolescence
January 16, 2018 - Exelixis Announces U.S. FDA Approval of Cabometyx (cabozantinib) Tablets for Previously Untreated Advanced Renal Cell Carcinoma
January 16, 2018 - Just How Often Do Patients Turn Post-Surgical Opioids Into a Habit?
January 16, 2018 - Opioid addiction – Genetics Home Reference
January 16, 2018 - Incomplete revascularization in PCI linked to higher mortality
January 16, 2018 - Machine learning algorithm uses brain scans to predict language ability in deaf children
January 16, 2018 - Penn scientists identify new therapeutic target for treatment of melanoma
January 16, 2018 - The London Clinic exhibits innovative technology to treat Parkinson’s disease at Arab Health
January 16, 2018 - Early influenza testing is critical to prevent serious complications
January 16, 2018 - Study Gets to the Core of Back Pain in Runners
January 16, 2018 - Year in Review: Ophthalmology | Medpage Today
January 16, 2018 - Marijuana Use
January 16, 2018 - Researchers create novel compound targeting melanoma cells
January 16, 2018 - FDA grants approval for first drug to treat inherited breast cancer
January 16, 2018 - Researchers develop remote-controlled mechanogenetics system to target and kill cancer cells
January 16, 2018 - Fresh, Frozen Embryos Equal in IVF
January 16, 2018 - Research shows biological clocks could improve brain cancer treatment
January 16, 2018 - Dire view from within accident and emergency wards of England and Wales
CGRP Blocker Proves Mettle as Migraine Tx

CGRP Blocker Proves Mettle as Migraine Tx

image_pdfDownload PDFimage_print

Action Points

  • The calcitonin gene-related peptide (CGRP) blocker galcanezumab bested placebo, meeting its primary endpoint of preventing episodic migraine.
  • Adverse events that were reported by 5% or more of patients in at least one galcanezumab group, and more frequently than placebo, included injection-site pain, upper respiratory tract infection, nasopharyngitis, dysmenorrhea, and nausea.

The calcitonin gene-related peptide (CGRP) blocker galcanezumab bested placebo in a phase IIb trial, meeting its primary endpoint of preventing episodic migraine.

A monthly subcutaneous injected dose of 120 mg of the investigational agent met the study’s primary objective: the posterior probability of greater improvement, measured by the mean change from baseline in the number of migraine headache days 9 to 12 weeks after randomization, compared with placebo versus 95% superiority threshold, reported David Dodick, MD, of the Mayo Clinic in Phoenix, and colleagues.

The drug also showed fewer migraine headache days from baseline, with an overall reduction of 4.3 days for patients treated with either 120 or 300 mg of galcanezumab versus 3.4 days for placebo (P=0.02), they wrote online in JAMA Neurology.

“This phase IIb study supported the favorable efficacy and tolerability results of a previous phase II study with galcanezumab, established the lowest effective dose, confirmed the therapeutic value of blocking the CGRP pathway in migraine, and supported phase III trials with galcanezumab for the preventive treatment of episodic and chronic migraine,” Dodick told MedPage Today.

Galcanezumab joins other CGRP blockers fremanezumab, erenumab (Aimovig), and eptinezumab that are being evaluated for migraine prevention. Previous galcanezumab trials have reported benefits over placebo, and manufacturer Eli Lilly announced on Dec. 11, 2017 that the FDA has accepted the Biologics License Application (BLA) to review the drug.

“The results of this study are consistent with those of other published studies evaluating the CGRP antibodies for prevention of migraine,” Elizabeth Loder, MD, MPH, of Brigham and Women’s Hospital in Boston told MedPage Today. “The treatment is clearly more effective than placebo, but the magnitude of the benefit is modest.”

“I would like to see a head-to-head trial with currently available preventive drugs,” added Loder, who was not involved in the study. “I suspect these new treatments might not prove to be more effective than existing drugs such as topiramate.”

Trial Details

In this double-blind trial, researchers enrolled patients, ages 18-65, who had four to 14 migraine headache days per month, and experienced migraine onset prior to age 50. Patients must have stopped botulinum toxin type A and B treatments at least 4 months before baseline.

The study ran from July 7, 2014 to Aug. 19, 2015 in the clinics of 37 licensed physicians and had four periods:

  • Period 1 (5-45 days): Initial screening and washout of migraine prevention treatments
  • Period 2 (28-38 days): Established baseline for migraine headache days; participants must have experienced at least 2 migraine attacks during this period to continue
  • Period 3: Patients randomized to one of five groups to receive subcutaneous injections of 5, 50, 120, or 300 mg of galcanezumab or placebo once monthly for 3 months
  • Period 4: 3-month post-treatment period in which patients received none of the tested treatments

The researchers allowed patients to take short-term migraine medications, excluding opioids or barbiturates, as needed. They permitted other preventive treatments only during study period 4, at the discretion of the investigator.

Baseline demographic and clinical characteristics were not statistically significantly different between any treatment groups. The patient population was primarily female (83.0%) and white (75.0%), with an average age of 40.2.

The primary objective was to determine whether at least one dose of galcanezumab was superior to placebo in preventing migraine. To be superior, the posterior probability of greater improvement for any galcanezumab dose group compared with placebo, measured by the mean change from baseline in the number of migraine headache days 9 to 12 weeks after randomization, had to be 95% or more.

For the primary endpoint, 120 mg of galcanezumab significantly reduced migraine headache days compared with placebo (99.6% posterior probability −4.8 days, 90% Bayesian credible interval −5.4 to −4.2 vs 95% superiority threshold −3.7 days, 90% BCI −4.1 to −3.2).

The overall change from baseline in the number of migraine headache days during study period 3 also was statistically significantly different for patients treated with both 120 mg (−4.3 migraine headache days; 95% CI −4.9 to −3.7, P=0.02) and 300 mg (−4.3 migraine headache days, 95% CI, −4.9 to −3.7, P=0.02) of galcanezumab, compared with placebo (−3.4 migraine headache days, 95% CI −3.8 to −2.9).

Adverse events that were reported by 5% or more of patients in at least one galcanezumab group, and more frequently than placebo, included injection-site pain, upper respiratory tract infection, nasopharyngitis, dysmenorrhea, and nausea.

“The very low discontinuation rate due to adverse events in this study reinforces the favorable tolerability profile of galcanezumab that will hopefully translate into improved patient adherence, compared to currently approved preventive options for episodic migraine, and long-term patient outcomes,” Dodick said.

Study limitations included its short duration, although the authors noted that a 3-month double-blind period is routine in migraine prevention trials. The 28-day baseline period, although standard, also may not have been long enough to establish an accurate baseline of headache frequency.

Finally, the researchers did not correct secondary endpoints for multiple comparisons; these should be interpreted with caution and viewed as preliminary, they wrote.

Concern for Pregnant Women

Galcanezumab’s 28-day half-life also may improve adherence since patients don’t need to take it daily, but could be a disadvantage if side effects occur, Loder noted.

“I particularly worry about this because we do not have good information on the safety of these antibody treatments in pregnancy, yet childbearing women are most severely affected by migraine and most likely to be using these treatments,” she said. “Roughly half of pregnancies are unintended, and if unintended pregnancy occurs shortly after taking an injection of this treatment, first trimester exposure will occur.”

“CGRP is a potent vasodilator and is widely distributed in the body, so it is likely that it plays an important role in many processes,” she added. “Galcanezumab appears to be well tolerated, although there are quite a number of respiratory and GI infections or inflammatory conditions, such as Crohn’s exacerbation, appendicitis, sinusitis, etc. That will be something to look for in future trials.”

The study was funded by Eli Lilly. Some co-authors are company employees.

Dodick disclosed relevant relationships with Allergan, Amgen, Alder, Arteaus, Pfizer, Colucid, Merck, NuPathe, Eli Lilly, Autonomic Technologies, Ethicon J&J, Zogenix, Supernus, Labrys, Boston Scientific, Medtronic, St Jude, Bristol-Myers Squibb, Lundbeck, Impax, MAP, Electrocore, Tonix, Novartis, Teva, Alcobra, Zosano, Insys, GBS/Nocira, Acorda, eNeura, Epien, GBS/Nocira, Second Opinion, IntraMed, SAGE Publishing, Sun Pharma, Oxford University Press, American Academy of Neurology, American Headache Society, West Virginia University Foundation, Canadian Headache Society, Healthlogix, Wiley, Universal Meeting Management, WebMD, UptoDate, Medscape, Oregon Health Science Center, Starr Clinical, Decision Resources, and Synergy. Co-authors disclosed multiple relevant relationships with industry.

  • Reviewed by
    Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner


last updated

Tagged with:

About author

Related Articles