Fremanezumab
(Synonyms: TEV-48125) 目录号 : GC66408
Fremanezumab (TEV-48125) 是一种人源化 IgG2a 单克隆抗体，可选择性且有效地与降钙素基因相关肽 (CGRP) 结合。CGRP 是一种 37 个氨基酸的神经肽，参与偏头痛的中枢和外周病理生理事件。Fremanezumab 具有用于慢性偏头痛研究的潜力。
Cas No.:1655501-53-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Fremanezumab (TEV-48125) is a humanized IgG2a monoclonal antibody that selectively and potently binds to calcitonin gene-related peptide (CGRP). CGRP is a 37-amino acid neuropeptide involved in central and peripheral pathophysiological events of migraine. Fremanezumab has the potential for chronic migraine research[1].
| Cas No. | 1655501-53-3 | SDF | Download SDF |
| 别名 | TEV-48125 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Fremanezumab for the Preventive Treatment of Chronic Migraine
N Engl J Med 2017 Nov 30;377(22):2113-2122.PMID:29171818DOI:10.1056/NEJMoa1709038.
Background: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), is being investigated as a preventive treatment for migraine. We compared two Fremanezumab dose regimens with placebo for the prevention of chronic migraine. Methods: In this phase 3 trial, we randomly assigned patients with chronic migraine (defined as headache of any duration or severity on ≥15 days per month and migraine on ≥8 days per month) in a 1:1:1 ratio to receive Fremanezumab quarterly (a single dose of 675 mg at baseline and placebo at weeks 4 and 8), Fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), or matching placebo. Both Fremanezumab and placebo were administered by means of subcutaneous injection. The primary end point was the mean change from baseline in the average number of headache days (defined as days in which headache pain lasted ≥4 consecutive hours and had a peak severity of at least a moderate level or days in which acute migraine-specific medication [triptans or ergots] was used to treat a headache of any severity or duration) per month during the 12 weeks after the first dose. Results: Of 1130 patients enrolled, 376 were randomly assigned to Fremanezumab quarterly, 379 to Fremanezumab monthly, and 375 to placebo. The mean number of baseline headache days (as defined above) per month was 13.2, 12.8, and 13.3, respectively. The least-squares mean (±SE) reduction in the average number of headache days per month was 4.3±0.3 with Fremanezumab quarterly, 4.6±0.3 with Fremanezumab monthly, and 2.5±0.3 with placebo (P<0.001 for both comparisons with placebo). The percentage of patients with a reduction of at least 50% in the average number of headache days per month was 38% in the fremanezumab-quarterly group, 41% in the fremanezumab-monthly group, and 18% in the placebo group (P<0.001 for both comparisons with placebo). Abnormalities of hepatic function occurred in 5 patients in each Fremanezumab group (1%) and 3 patients in the placebo group (<1%). Conclusions: Fremanezumab as a preventive treatment for chronic migraine resulted in a lower frequency of headache than placebo in this 12-week trial. Injection-site reactions to the drug were common. The long-term durability and safety of Fremanezumab require further study. (Funded by Teva Pharmaceuticals; ClinicalTrials.gov number, NCT02621931 .).
Fremanezumab for the prevention of chronic and episodic migraine
Drugs Today (Barc) 2019 Apr;55(4):265-276.PMID:31050694DOI:10.1358/dot.2019.55.4.2970909.
On September 15, 2018, the U.S. Food and Drug Administration (FDA) approved subcutaneous Fremanezumab, a calcitonin gene-related peptide (CGRP) monoclonal antibody, for the treatment of episodic and chronic migraine in adults, with two recommended dosages: 225 mg monthly or 675 mg every 3 months. On March 28, 2019, the European Commission granted Fremanezumab Marketing Authorization in the E.U. for the same indication. In this monograph we review data on the pharmacokinetics, metabolism and safety of Fremanezumab as reported in the scientific literature from phase I to phase III studies. Fremanezumab demonstrated a very low incidence of adverse events. Primary and secondary endpoints in randomized, controlled trials on the efficacy of Fremanezumab were achieved. Fremanezumab was demonstrated to be able to reduce the number of migraine days, headache hours and number of days with use of acute treatment agents. No data on drug-drug interactions with Fremanezumab are available. However, it is worth mentioning that Fremanezumab showed a very low incidence of development of adverse drug antibodies compared with other CGRP antibodies.
Migraine overview and summary of current and emerging treatment options
Am J Manag Care 2019 Jan;25(2 Suppl):S23-S34.PMID:30681821doi
Migraine is a leading cause of disability worldwide. Approximately 15% of Americans experience migraines. Most people who have migraines feel that people who do not have them often underestimate their condition. Migraines affect people's quality of life and ability to participate in work, family, and social events. A new class of medication, calcitonin gene-related peptide (CGRP) antagonists, has been approved for migraine prevention in adults. The newly approved CGRP antagonists are erenumab, Fremanezumab, and galcanezumab, while eptinezumab looks to 2020 for approval. Lasmiditan, ubrogepant, and rimegepant are currently emerging acute migraine therapies that may be added to the arsenal of current migraine management.
Fremanezumab versus placebo for migraine prevention in patients with documented failure to up to four migraine preventive medication classes (FOCUS): a randomised, double-blind, placebo-controlled, phase 3b trial
Lancet 2019 Sep 21;394(10203):1030-1040.PMID:31427046DOI:10.1016/S0140-6736(19)31946-4.
Background: Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of Fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications. Methods: The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly Fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly Fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed. Findings: Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly Fremanezumab (n=276), or monthly Fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterly Fremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI -3·8 to -2·4]; p<0·0001) and with monthly Fremanezumab (LSM change -4·1 [0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverse events were similar for placebo and Fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly Fremanezumab, and four (1%) of 285 with monthly Fremanezumab. Interpretation: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications. Funding: Teva Pharmaceuticals.
Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial
JAMA 2018 May 15;319(19):1999-2008.PMID:29800211DOI:10.1001/jama.2018.4853.
Importance: Fremanezumab, a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, may be effective for treating episodic migraine. Objective: To assess the efficacy of Fremanezumab compared with placebo for prevention of episodic migraine with a monthly dosing regimen or a single higher dose. Design and setting: Randomized, double-blind, placebo-controlled, parallel-group trial conducted at 123 sites in 9 countries from March 23, 2016 (first patient randomized), to April 10, 2017, consisting of a screening visit, 28-day pretreatment period, 12-week treatment period, and final evaluation at week 12. Participants: Study participants were aged 18 to 70 years with episodic migraine (6-14 headache days, with at least 4 migraine days, during 28-day pretreatment period). Patients who had previous treatment failure with 2 classes of migraine-preventive medication were excluded. Interventions: Patients were randomized 1:1:1 to receive subcutaneous monthly dosing of Fremanezumab (n = 290; 225 mg at baseline, week 4, and week 8); a single higher dose of Fremanezumab, as intended to support a quarterly dose regimen (n = 291; 675 mg of Fremanezumab at baseline; placebo at weeks 4 and 8); or placebo (n = 294; at baseline, week 4, and week 8). Main outcomes and measures: The primary end point was mean change in mean number of monthly migraine days during the 12-week period after the first dose. Results: Among 875 patients who were randomized (mean age, 41.8 [SD, 12.1] years; 742 women [85%]), 791 (90.4%) completed the trial. From baseline to 12 weeks, mean migraine days per month decreased from 8.9 days to 4.9 days in the Fremanezumab monthly dosing group, from 9.2 days to 5.3 days in the Fremanezumab single-higher-dose group, and from 9.1 days to 6.5 days in the placebo group. This resulted in a difference with monthly dosing vs placebo of -1.5 days (95% CI, -2.01 to -0.93 days; P < .001) and with single higher dosing vs placebo of -1.3 days (95% CI, -1.79 to -0.72 days; P < .001). The most common adverse events that led to discontinuation were injection site erythema (n = 3), injection site induration (n = 2), diarrhea (n = 2), anxiety (n = 2), and depression (n = 2). Conclusions and relevance: Among patients with episodic migraine in whom multiple medication classes had not previously failed, subcutaneous Fremanezumab, compared with placebo, resulted in a statistically significant 1.3- to 1.5-day reduction in the mean number of monthly migraine days over a 12-week period. Further research is needed to assess effectiveness against other preventive medications and in patients in whom multiple preventive drug classes have failed and to determine long-term safety and efficacy. Trial registration: clinicaltrials.gov Identifier: NCT02629861.