Hi all,

I know the drug "Lasmiditan" has had a mention or two on the board before, possibly referred to by it's candidate drug number, whilst in early development stages. It has been looked at for further development in the last couple of years and I have been following it's progress with interest.

I should posthumously thank Barry T Coles for first making me aware of the "Ditans" as a drug group and before he departed, encouraging me to follow up on their development. The idea of a "highly selective 5-HT(1F) receptor agonist without vasoconstrictor activity" seemed rather appealing to both Barry and myself.

The promise of daily relief...ahhh... ;D

With so many potential drugs falling over at trial phase 2, like the CGRP receptor antagonists, it's good to see a new one get regulatory approval and show up on shelves.

I am aware that thus far, only Migraine is mentioned in the literature and that there are side-effect issues and adverse outcomes to be overcome, as with any drug.

For those who know and understand the story behind Sumatriptan and how it came to be used in Cluster Headache, those same people with the experience and vision to look beyond the term "Migraine" may see the potential in this drug for CH and also, the appeal of possibility.

2011-2012 literature showed a couple of inconclusive trials that required "Further assessment" of the drug.

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A more recent evaluation:


Quote:

Summary Future Neurology November 2013 Vol. 8, No. 6, Pages 631-638 , DOI Drug Evaluation Lasmiditan for acute migraine treatment Lars Neeb1 & Uwe Reuter*1 "Lasmiditan is a new neurally acting antimigraine drug that acts as a highly selective serotonin1F receptor agonist. Its chemical structure is distinctly different from that of triptans. Its dose-dependent clinical efficacy was proven in two clinical Phase II trials using intravenous and oral formulations. Oral lasmiditan showed significant headache relief after 2 h at doses of 50, 100, 200 and 400 mg. Adverse events of lasmiditan were dose-dependent and mainly associated with the CNS. They predominantly included dizziness, paresthesia and fatigue, and were mostly mild-to-moderate in intensity. Preclinical studies showed that, unlike triptans, lasmiditan lacks any vasoconstrictive activity, which makes it a promising drug for patients with contraindications to triptans owing to cardio- or cerebro-vascular diseases, or an elevated vascular risk profile."

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Lasmiditan appears to have shown up in South Korea and South East Asia, meaning it must have met some form of regulatory approval and may possibly be available for import. If it has hit shelves there, it may also be sought for import by prescribing specialists for "off-label", "experimental", or on the grounds "compassionate use", in cluster headache.

Just this past few weeks, this press release shows that the drug may have hit some shelves in South East Asia.


Quote:

CoLucid signs distribution and supply agreement with ILDONG for Lasmiditan Published on October 23, 2013 at 12:30 AM CoLucid Pharmaceuticals, Inc., and ILDONG Pharmaceutical Co., Ltd., announced today that they have entered into a distribution and supply agreement for Lasmiditan in South Korea and Southeast Asia. Under the terms of the agreement, CoLucid will receive upfront and milestone payments in addition to consideration for product supply in exchange for exclusive rights to ILDONG for development and commercialization of Lasmiditan in the territory. ILDONG will be responsible for the costs and activities related to development and regulatory approvals in the territory and will also participate in key registration trials as part of the global development plan. "We are very happy to announce the collaboration with ILDONG.  We look forward to working together with such a strong partner to bring Lasmiditan to the market to meet the many unmet needs of migraine sufferers," said Thomas P. Mathers, CEO of CoLucid. ILDONG Pharma Chairman and CEO, Jung-chi Lee, Ph.D., commented, "We expect CoLucid's innovative drug, Lasmiditan, to be successfully developed under our partnership and be subsequently well positioned to perform in the Korean market and Southeast Asia in the near future.  We are sure that this will provide us a further opportunity to strengthen the relationship between our two companies." SOURCE CoLucid Pharmaceuticals, Inc; ILDONG Pharmaceutical Co., Ltd.

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Whether or not this one falls over, nobody will know.
Whether or not it is even appropriate for use in CH, we do not yet know. I have noted the so far, variable dose range in relation to outcomes in Migraine relief and also that aside from oral forms, an intravenous form may be available.

It would be nice to see if an auto-injector whack of this stuff at the correct dose has as beneficial effect as Imigran/Imitrex, without all the issues associated with the vasoconstrictive side-effects of Sumtriptan.

Lasmiditan, if successful, would finally help to rule in or out the long-held belief in "Vascular theory" in headache disorders...

I will post for the site on any case studies, any trials, or any recorded use of Lasmiditan in CH. I cannot yet locate them, but I will post Product Information sheets (PI) and Consumer Medical Information data sheets (CMI) on Lasmiditan when and if they become available.

Cheers, Ben.

Thanks Ben, our family here is incredibly indebted to the research types, like you, Bob Johnson, Batch, and many others, who keep poking sticks at this stuff. Please know how appreciated your work is. [smiley=hug.gif]

Joe

Thanks for the update Ben. It would be great for people who can't use triptans to have another option available.

I've located a product information sheet for Lasmiditan, from CoLucid, it's one of those annoying giant PDF posters, but includes some very interesting data for those interested:

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If I read between the lines... When they dial in and settle on a delivery method, tablet, fast dispersion tablet, nasal spray, IV infusion...whatever methods they finalise, and also a therapeutic dosage range, Lasmiditan looks like it could hold off Migraine, *possibly CH?* for many hours.

Of course this will be subject to perhaps more trials, or just plain "off-label" use to see it shifted across for use in CH, which is not too hard to achieve these days...

Looking at the plasma concentration/time graphs, time to headache relief is fairly long. But the Triptan graphs often look like this, with users reporting relief sooner than graph data would typically show.

Lasmiditan is directly compared by the manufacturer with the Sumatriptan Nasal Spray profiles for time to onset of relief. It is also compared in a number of ways with a handful of triptans. The duration of action of this drug far exceeds any triptan, without any demonstrated vasoconstrictive properties, so dare I say it? Possibly 18 ours relief, with no triptan rebound attack?

Could it be?

That would be good for those of us who are in the 4-6 (or more) attack per day range.

It may be useful as a transitional drug, instead of pred, to buy time during initial presentation and correct differential diagnosis. It could even be a bout breaker.
We don't know, but live in hope anyways...

And a few others for those interested in reading the studies...

The 5-HT1F receptor agonist lasmiditan as a potential treatment of migraine attacks: a review of two placebo-controlled phase II trials
Peer C. Tfelt-Hansen • Jes Olesen:

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Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan:

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Efficacy and tolerability of lasmiditan, an oral 5-HT1F receptor agonist, for the acute treatment of migraine:
a phase 2 randomised, placebo-controlled, parallel-group, dose-ranging study:

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An overview of migraine management and treatment:

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Very interesting...

Cheers, Ben.