From LBR-101 to Fremanezumab for Migraine

@article{Bigal2018FromLT,
  title={From LBR-101 to Fremanezumab for Migraine},
  author={Marcelo Eduardo Bigal and Alan M. Rapoport and Stephen D. Silberstein and Sarah Walter and Richard Hargreaves and Ernesto Aycardi},
  journal={CNS Drugs},
  year={2018},
  volume={32},
  pages={1025-1037}
}
Calcitonin gene-related peptide (CGRP) is a neuropeptide of importance in migraine pathogenesis. Its central role in migraine was proven pharmacologically by the development of CGRP receptor antagonists. Monoclonal antibodies targeting CGRP or its receptor are effective in the preventive treatment of episodic and chronic migraine and are considered potential breakthroughs in their treatment. Fremanezumab (previously known as TEV-48125, LBR-101, or RN-307) is a humanized IgG2a monoclonal… 

Fremanezumab as a preventive treatment for episodic and chronic migraine

TLDR
Fremanezumab was shown to be effective in episodic and chronic migraine, with a monthly and quarterly dose of administration, as monotherapy and add-on therapy, and the effect seems to be maintained over time.

Calcitonin Gene‐Related Peptide Modulators – The History and Renaissance of a New Migraine Drug Class

TLDR
Data indicated that the therapeutic site of action of the CGRP‐RAs was peripheral not central; that IV C GRP had most likely evoked migraine through an action at sites outside the blood‐brain barrier; and that migraine pain was therefore, at least in part, peripheral in origin.

An Evidence-Based Review of Fremanezumab for the Treatment of Migraine

TLDR
This review provides an update on the epidemiology, pathogenesis, diagnosis, and current treatment of migraine, and summarizes the evidence for fremanezumab as a treatment for migraine.

Monoclonal Antibodies Targeting CGRP: From Clinical Studies to Real-World Evidence—What Do We Know So Far?

TLDR
The latest clinical evidence for the use of anti-CGRP in migraine prevention with emphasis on efficacy and safety outcomes from Phase III and real-world studies is provided.

The Anti-CGRP Antibody Fremanezumab Lowers CGRP Release from Rat Dura Mater and Meningeal Blood Flow

TLDR
Fremanezumab lowers the CGRP release and lasts up to four weeks, thereby lowering the C GRP-dependent meningeal blood flow, which is relevant for the generation of migraine pain.

Population pharmacokinetic modelling and simulation of fremanezumab in healthy subjects and patients with migraine

TLDR
The population pharmacokinetics of fremanezumab were characterized in healthy subjects and patients with chronic migraine and episodic migraine, including the effects of intrinsic and extrinsic factors on PK variability.

Scaling Approaches for Pediatric Dose Selection: The Fremanezumab (AJOVY®) Journey to Select a Phase 3 Dose Using Pharmacokinetic Data from a Phase 1 Study

TLDR
A thorough evaluation was conducted to further characterize the population PK of fremanezumab and assess the predictive performance of the adult population PK model when applied to the Phase 1 pediatric data, the predictive performances of alternative pediatric population PK models, and the predictiveperformance of the selected pediatric populationPK model via a noncompartmental-based approach.

Optimal treatment strategy of fremanezumab in migraine prevention: a systematic review with network meta-analysis of randomized clinical trials

TLDR
The surface under the cumulative ranking curve (SUCRA) was used to determine the effects of the medication strategies of fremanezumab and exhibited the optimal balance between efficacy and safety within three months.

Real world preventative drug management of migraine among Spanish neurologists

TLDR
The initial management of migraine among Spanish Neurologists is in line with most guidelines, where first choice preventative drugs are concerned, but the Management of episodic migraine differed from chronic migraine, both in terms of neurologist preference and in their perceived efficacy.

References

SHOWING 1-10 OF 71 REFERENCES

TEV-48125: a Review of a Monoclonal CGRP Antibody in Development for the Preventive Treatment of Migraine

TLDR
The in vitro and in vivo pharmacology of TEV-48125 is discussed as well as highlighting its safety profile through the six Phase 1 studies that have been conducted, and the current state of development and future studies for TEV -48125 will be reviewed.

Monoclonal Antibodies for Migraine: Preventing Calcitonin Gene-Related Peptide Activity

TLDR
An overview of the role of CGRP in the pathophysiology of migraine is provided, followed by a review of the clinical development of CgrP-RAs, and some basic concepts on antibodies are discussed along with the publicly disclosed information on the development of mAbs targeting the C GRP pathway.

Calcitonin Gene-Related Peptide-Targeted Therapies for Migraine and Cluster Headache: A Review

TLDR
A growing body of clinical trials studying CGRP-targeted therapies for migraine and cluster headache is discussed, including two monoclonal antibodies in clinical trials for cluster headache prevention and several other small-molecular C GRP receptor antagonists in earlier stages of development.

Calcitonin gene-related peptide: an update on the biology

TLDR
The advent of CGRP receptor antagonists as a novel therapy for migraine attacks may represent a new era in the acute management of migraine, and this group of drugs may become an outstanding option for patients with cardiovascular disease, given the lack of associated vasoconstriction.

Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.

TLDR
The CGRP antagonist BIBN 4096 BS was effective in treating acute attacks of migraine and showed significant superiority over placebo with respect to most secondary end points.

Blocking CGRP in migraine patients – a review of pros and cons

TLDR
It is suggested that, based on current knowledge, the pros of blocking CGRP in migraine patients exceed the cons, and the efficacy of these drugs is in line with other currently used prophylactic treatments.

Therapeutic antibodies against CGRP or its receptor.

TLDR
Why CGRP is an ideal target for the prevention of migraine is reviewed and four monoclonal antibodies against either C GRP or its receptor that are in clinical development for the treatment of both episodic and chronic migraine are described.

Selective Inhibition of Trigeminovascular Neurons by Fremanezumab: A Humanized Monoclonal Anti-CGRP Antibody

TLDR
It is shown that, if given enough time, a CGRP-mAb can prevent the activation and sensitization of high-threshold (central) trigeminovascular neurons by cortical spreading depression, but not their activation from the skin or cornea, suggesting a potential explanation for selectivity to migraine headache, butNot other pains, and a predominantly peripheral site of action.

CGRP as the target of new migraine therapies — successful translation from bench to clinic

TLDR
Treatments that target calcitonin gene-related peptide (CGRP) and its receptor are proving effective for migraine treatment, and the hypothesis that CGRP has a major role in migraine pathophysiology is strongly supported.

Calcitonin Gene‐Related Peptide (CGRP) and Migraine Current Understanding and State of Development

TLDR
The role of C GRP in normal physiology and the consequences of CGRP inhibition for human homeostasis are discussed and the current state of development for CGRp‐receptor antagonists and CGRPs monoclonal antibodies is reviewed.
...