Pipeline migraine drugs
Currently, the drug development pipeline is rich with products nearing market availability for both the prevention and treatment of migraine. The most prominent focus of this pipeline activity is a new and very promising category of drug products known as CGRP (calcitonin gene-related peptide) antagonists. Researchers have determined that CGRP levels are highly elevated in migraine sufferers, and medications that can bind to and inhibit the activity of CGRP may yield significant value in helping to better manage migraine and cluster headache.
There are currently four CGRP antagonists in late-stage development. Recent late-stage clinical trials with these drugs demonstrate significant reductions in monthly migraine or headache days compared to placebo, and with minimal side effects, according to a study published in Current Treatments in Neurology.
Other abortive treatment pipeline drugs include:
- Lasmiditan, an investigational, first-in-class molecule for the acute treatment of migraine. It is the only oral drug in development of its kind that selectively targets 5-HT1F receptors, including those expressed in the trigeminal pathway, and has been designed for the acute treatment of migraine without the vasoconstrictor activity associated with some migraine therapies. If approved, lasmiditan could represent the first significant innovation for the acute treatment of migraine in more than 20 years.
In December 2017, Lilly announced positive results from the second of two phase 3 studies evaluating lasmiditan for the acute treatment of migraine. Lilly plan to submit a New Drug Application (NDA) for lasmiditan to the FDA in the second half of 2018.
- Ubrogepant, a novel, highly potent, orally-administered CGRP antagonist from Allegan is being evaluated for the acute treatment of migraine. Ubrogepant met its main goals in the first of two phase 3 studies. In a trial of 1,327 adults with migraines, ACHIEVE-1, the drug bested a placebo at reducing the pain or symptoms from a single “moderate to severe” attack. Results of the second phase 3 trial, ACHIEVE II, are expected in coming months. Allergan anticipates filing of a New Drug Application (NDA) to the FDA in 2019.
To be determined
While all of these agents offer the neurology community and migraine sufferers renewed hope for additional treatment alternatives, such hope must be balanced with questions that will remain largely unanswered at product introduction:
- Long-term data with use of these agents is largely limited at this point, and as such, whether these products provide long-term reliable durability of effect, safety and tolerability remains to be determined, according to the Current Treatments in Neurology study.
- While safety and tolerability of these products in clinical trials thus far appears good, it must be recognized that CGRP has many complex functions in the nervous and vascular systems. CGRP receptors are also found in the adrenal glands, kidneys, pancreas, and bone. There is at least a theoretical risk that blocking CGRP could hinder any beneficial physiologic functions CGRP activity may provide. And, since the activities of these drugs have been shown to be prolonged in the body, any undesirable effects may not be quickly and easily reversed, according to the Current Treatments in Neurology study.
- Pricing of these products will not be determined until product launch, however analysts estimate pricing for preventive CGRP antagonists could range from about $8,500 to $20,000 per year, according to The Verge. Without direct comparative data demonstrating enhanced safety and efficacy versus current standards of migraine care (both preventative and abortive), cost effectiveness with these therapies will remain to be determined.