CGRP stands for Calcitonin Gene-Related Peptide. It is a calcitonin group compound made up of polymers of amino acid monomers. CGRP is manufactured in the human body in the nerve cells (neurons) of the central nervous system and the peripheral nervous system.
Research – New Migraine drugs In The Pipeline (1)
So what is the function of CGRP? Of the many functions, CGRP is a powerful vasodilator and it contributes significantly in the transmission of pain message through the body. It is also believed to play a critical role in cardiovascular homeostasis as well as in processing noxious stimuli that has the potential to damage the tissues of the heart.
The development of drugs which are essentially CGRP receptor antagonist is in the pipeline aimed at helping migraineurs the world over cull the pain of their migraine episodes. How does the CGRP receptor antagonist do this? It has been observed that during the onset of a migraine attack, CGRP binds to CGRP receptors and activates these receptors which then transmit pain signals. CGRP receptor antagonist prevents the CGRP from binding on to CGRP receptors thus circumventing the transmission of pain signals causing migraine pain.
Telecagepant was such a CGRP receptor antagonist drug developed by Merck & Co. and was undergoing Phase III clinical trials but the trials were abandoned after identification of two patients with significant elevations in serum transaminases indicating liver damage. However, similar drugs without such side-effects are now being designed. CGRP receptor blockers also significantly reduce nausea and are more desirable in total benefit than triptans. As per Peter Goadsby, MD, PhD, director of UCSF’s Headache Center, “So this is a way for it to be effective and adds a safety bonus to the patients and it seems to be better tolerated.” (2)
There is another approach to drug design and development aimed at reducing the misery of migraineurs and it comes from the side of serotonin activity. In this class, one investigational drug of note is Lasmiditan thought of by Eli Lilly & Co and being designed to treat acute migraine by CoLucid Pharmaceuticals. These drugs are technically serotonin receptor agonists and selectively bind to the 5-HT1F receptor subtype. Unlike triptans these drugs do not constrict the heart vessels and have lesser side-effects. Trials have shown that administration of this drug reduced migraines to almost nothing within a two-hour period in almost 60% of the patients also tackling nausea and photophobia beautifully. The drug is expected to be ready by 2014. As per Dr. Goadsby, “Lasmiditan is now that finished its phase two studies and clearly works. It does not have the same sort of liver effects as its predecessors and will move on into phase three. That is again for acute migraine treatment. So it is a safe and totally different action than what we currently have.” (2)
Health Canada has given a notice of compliance/approval to Stellar Pharmaceuticals’ generic drug Cambia. Cambia is used for the treatment of acute migraines in adults with or without aura. The chemical composition of this oral solution comprises of diclofenac potassium. Cambia is actually manufactured by Tribute Pharmaceuticals, a wholly owned subsidiary of Stellar Pharmaceuticals. (1)
Cambia (R) – Diclofenac Potassium Approved In Canada For Migraineurs(2)
This is a relief to the Canadian migraineurs as the generic drug is affordable. In Canada Cambia will be marketed exclusively by Nautilus Neurosciences. Oral tablets of diclofenac potassium have been available to the U.S patients since May 2010 after FDA approval. Diclofenac Potassium is a non-steroidal anti-inflammatory drug (NSAID) and a benzeneacetic acid derivative.
Cambia and other brands of diclofenac potassium are contraindicated for use in persons with cardiovascular condition, peri-operative pain in the setting of coronary artery bypass graft and those with gastrointestinal sensitivity and conditions.
According to Rob Harris, President and CEO of Stellar Pharmaceuticals, “We feel that CAMBIA(R) represents a logical first line prescription treatment choice for acute migraine, especially when over-the-counter medicines that offer some relief with milder forms of migraine pain fail, and where side effects or tolerability issues with the triptan class of drugs becomes a concern. With CAMBIA(R), Canadian physicians now have a new treatment option with comparable efficacy to the oral triptans but with a faster onset of action.”(3)
A plastic surgeon at the University Of Texas South-western Medical Center has developed a new surgical technique that uses Botox which is generally employed for cosmetic surgeries in treating migraines.
New Surgical Technique Using Botox Promises Relief To Migraineurs (1)
In the procedure, the probable peripheral nerve triggers are first identified and then Botox administered at those sites during the surgery. These sites would be those that the doctor thinks are the ones contributing towards the migraine pain. This method is not recommended for everyone and is said to be prescribed to migraineurs on case-to-case basis.
Dr. Jeffrey Janis, has come up with this technique based on 5 years of study on anatomies of animals where nerves were decompressed to provide long-lasting relief to acute pain. In one of his recent studies, Dr. Janis exhibited the success of his technique. The study found that the use of Botox in the surgery led to average improvement of 85.5 percent over original symptoms such as frequency, severity and duration — but surgery produced a 96.6 percent average improvement over original symptoms.
However, according to Dr. Janis, “This type of surgery is not for everyone, but for those who have not found relief, these procedures are proving effective.” (2)
Teva Pharmaceuticals U.K have launched generic Naratriptan for migraineurs in the U.K. today. Teva is a pharma major in the U.K with share in the generic drugs, branded respiratory and hospital care market
The generic Naratriptan is thus a cheaper and more affordable option by migraineurs. The generic Naratriptan is four times cheaper than the branded version of the same chemical (Naratriptan hydrochloride). It has been released as film-coated tablets of potency 2.5 mg in two pack sizes. This generic form targets to manage the acute headache phase of a migraine episode that is accompanied with or without an aura.
According to Teva UK’s Commercial Director, Kim Innes, “We want to make more medicines accessible for more people and Naratriptan is our fifth day-one launch this year to add to our portfolio of over 700 products. It’s good for Pharmacy because patent expiries provide opportunities for increasing margins and keeping costs down. Importantly, it also means we continue to help save the NHS over £9bn on generic prescriptions.” (2)
Naratriptan is a prescription drug that must be taken strictly as per doctor’s instructions. Naratriptan for migraine is contraindicated if the person has high blood pressure, chest pain, diabetes, stroke, liver conditions, kidney disease or epilepsy.
The US Patent and Trademark Office has issued MAP Pharmaceutical Inc’s new drug under the banner, “Method of Therapeutic Administration of DHE to Enable Rapid Relief of Migraine while Minimizing Side Effect Profile.”
Pulmonary Administration DHE from MAPP Issued Patent (1)
The drug’s primary ingredient DHE or Dihydroergotamine is MAPP’s proprietary formulation. The novelty of this new formulation is that it has proved to have rapid efficacy in curbing migraine pain but minimizes the adverse effects that other migraine formulations have.
To be able to achieve quick distribution, metabolization and excretion of the drug, the DHE drug involves pulmonary administration or inhalation of the drug. This is advantageous as the results are almost instantaneous because the drug does not undergo a ‘first-pass effect’ and is absorbed almost entirely into the general blood circulation through the lungs.
The drug has been named LEVADEX® is an orally inhaled investigational drug administered using the Company’s proprietary TEMPO® inhaler for the potential acute treatment of migraine in adults and targets the pharmacokinetic profiles described in this patent. DHE is a drug that is currently available in other dosage forms to treat migraine. (2)