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37223811000001103

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

AjovyEpisodic and chronic migraine - prevention in adults

Information

Ajovy
New molecular entity
Teva
Teva

Development and Regulatory status

Launched
Launched
Launched
July 2019
Jul 19Launched in the EU. Price 225mg solution for injection in prefilled syringe, 1=£450.00 [17].
Jun 19Has been available in the US since Sep 18 [16].
Apr 19Approved in the EU [15].
Jan 19Recommended 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 the drug be prescribed by physicians experienced in the treatment of migraine [14].
Sep 18Approved in US for quarterly and monthly dosing for the preventive treatment of migraine in adults [12] .
Sep 18Will be priced at $6,900 per year in the US (same as erenumab) [13].
Feb 18Approval is likely to be delayed in the US as the FDA has issued a warning letter to the Celltrion plant that makes fremanezumab about violations in Good Manufacturing Practice (GMP) [10]
Feb 18The EMA has accepted the Marketing Authorization Application (MAA) for fremanezumab, an anti-calcitonin gene-related peptide (CGRP) antibody for the prevention of episodic and chronic migraine in adults [9].
Dec 17Teva has acquired a priority review voucher to speed up the review of fremanezumab, and expects a regulatory decision by middle of next year [8]
Oct 17Filed in US [7].
Jun 17Teva plan to submit a Biologics License Application to the FDA for fremanezumab later this year, based on results from NCT02621931 [4].

Category

Calcitonin gene-related peptide receptor antagonist
Migraine affects about 6% of men and 18% of women [3].
Episodic and chronic migraine - prevention in adults
Subcutaneous

Further information

Yes
To be confirmed

Trial or other data

May 18Results of PIII NCT02629861 published in JAMA. RCT (n=875) found both monthly dose and single high dose fremanezumab resulted in larger decreases in migraine days per month vs placebo (difference of 1.5 days and 1.3 days vs placebo respectively, p<0.001 for both) [11].
Jun 17Teva announce positive results from the second PIII HALO study of fremanezumab. Fremanezumab given monthly improved the average number of migraine days, relative to baseline, by 41.6% for the duration of the trial (-3.7 days vs -2.2 days for placebo, p < 0.0001). Number of days with disability were decreased by 64.7% (p =0.0021) and medication consumption was decreased by 39.0% ( p < 0.0001). The quarterly SC dose also yielded significant results for decrease in migraine days (-3.4 days or 37.0%, p < 0.0001) and for all other comparisons. Both dose regimens significantly improved migraine in subjects on stable doses of other prophylactic medications (-4.0 days for monthly dose vs -2.0 days for placebo, p = 0.001; -3.7 days for quarterly dose, p = 0.006) [6].
Jun 17PIII study (NCT02638103) to evaluate long-term safety, tolerability, and efficacy of SC administration of TEV-48125 in adult patients with CM or EM is ongoing in EU and US. Estimated primary completion date is Sept 2018 [5].
May 17Teva announce PIII NCT02621931 met primary endpoint of reduction in number of monthly headache days of at least moderate severity during the 12 week period, for monthly (-4.6) and quarterly (-4.3 days) dosing regimens vs. placebo (-2.5 days, p<0.0001 for both) [4].
May 17In CM (NCT02621931), 1,130 patients were randomized in a 1:1:1 ratio to receive SC fremanezumab 675 mg at initiation followed by monthly 225 mg for 2 months (monthly dose regimen), 675 mg at initiation followed by placebo for 2 months (quarterly dose regimen), or three monthly doses of matching placebo. Primary efficacy endpoint was mean change from baseline (28-day run-in period) in monthly average number of headache days of at least moderate severity during the 12-week period after the first dose of fremanezumab [4].
May 17HALO research programme comprises two 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group PIII studies of fremanezumab in episodic (EM) and chronic (CM) migraine. Studies consist of a screening visit, a 28-day run-in period, 84-day treatment period, and end-of-treatment [EOT] visit 28 days after the final dose of study drug. Studies aim to compare safety, tolerability, and efficacy of four dose regimens of SC fremanezumab vs placebo in adults with episodic and chronic migraine [4].
Sep 15Results of PII randomised trial (NCT02025556), investigating safety, tolerability, and efficacy of TEV-48125 for preventive treatment of high-frequency episodic migraine, published in the Lancet Neurology. TEV-48125 reduced the number of migraine days during weeks 9-12 of the study at both doses tested (mean difference in change from baseline vs. placebo of -2.81 days for 225mg and -2.64 days for 675mg) [2].
Sep 15Results of PII randomised trial (NCT02021773), investigating safety, tolerability and efficacy of TEV-48125 for preventive treatment of chronic migraine, published in the Lancet Neurology. TEV-48125 reduced the number of headache-hours during weeks 9-12 of the study at both doses tested (mean difference in change from baseline vs. placebo of -22.74 hours for 675/225mg and -30.41 hours for 900mg) [1].

Evidence based evaluations