‘Game changing’ migraine drugs on the horizon

Thirty-six million Americans, about 12% of the population, suffer from migraine headaches, according to the American Migraine Foundation. The condition costs the United States more than $20 billion each year; costs are attributed to direct medical expenses, such as doctor visits and medications, as well as indirect expenses such as missed work and lost productivity.

Patients who have migraines can represent a sizeable population in an employer’s benefit, with a high degree of utilization of various products, both for acute treatment and prevention, according to Nadina Rosier, PharmD, Health and Benefits practice leader, Pharmacy, Willis Towers Watson.

“Moreover, there are potential absence, productivity, and disability implications for payers that should be considered in the overall management of their benefits budgets,” she says. “Employers may look to health insurers to help address the lost time with helping employees get back to work.  Some preventive anti-migraine drug therapies may  not have complete effectiveness for each patient  and many of these drugs have cumbersome side effects that cause patients to become noncompliant. For example, some patients may not respond to treatments or some of the treatments such as triptans or dihydroergotamine, are contraindicated for patients with high blood pressure or coronary artery disease.”

Clinicians also need to examine whether the pain may be a symptom of another issue rather than a migraine headache, Rosier points out.

Migraine treatments

There is presently no silver-bullet treatment for migraines, says Cynthia Ambres, MD, KPMG strategy partner and a member of the firm’s Global Healthcare Center of Excellence. 

“The treatments are getting more precise as we learn more about the cause of migraines,” she says. “There may be less trial and error in alleviating migraine symptoms and causes as more personalized treatments hit the market. Newer drugs may add treatment costs, but the condition is debilitating and one the medical community has struggled treating for decades.”

Since most migraine medications are now generic, new pharmaceutical developments are mainly different dosage forms or new methods of administration for existing drugs-such as a nasal spray previously only taken orally, says April Kunze, director of formulary development and pipeline, Prime Therapeutics.

“Some manufacturers are also bringing new combination brands to market that contain triptans with nonsteroidal anti-inflammatory drugs. We anticipate very little use of the new products and will manage by encouraging use of effective, low-cost generic options.”

A combination of both acute medications and preventive medications can provide relief for migraine sufferers, adds Rosier. “Depending on the use of brand versus generic products, oral versus injectables, a payer’s costs associated with use of these products varies,” she says.

Acute medications for migraine sufferers include those used for pain management, such as opioids and ibuprofen. Patients also use triptans, most of which are available in generic form. Preventive drugs used on a chronic basis include beta-blockers and calcium channel blockers which are also used in the treatment of high blood pressure. “Antidepressants and ant-seizure medications have also been used by some sufferers as preventive treatment,” she says. 

OnabotulinumtoxinA (Botox, Allergan) for injection has also been indicated for chronic migraines with injections across the head and neck, but is more expensive treatment, according to Rosier.

Next: Prevention a top focus

Prevention a top focus

Several companies are in the late stages of developing treatments that prevent the onset of migraines that target calcitonin gene-related peptide (CGRP)-receptors, which are involved in the brain’s pain signaling during migraines.

 “The CGRP antibodies could be a game changer as phase 2 trials for four products are showing promising results,” Rosier says. “FDA approval [for these drugs] could be as early as 2018.”

Teva’s TEV-48125, a humanized monoclonal CGRP antibody investigational treatment, is being developed for the prevention of chronic migraine and high frequency episodic migraine. Eli Lilly’s LY2951742, a CGRP neutralizing antibody, is also being investigated. Alder BioPharmaceuticals recently reported that its monoclonal antibody injected quarterly to prevent migraines in patients with chronic conditions (ALD403), succeeded in a clinical trial.

Similary, Amgen’s AMG 334, a human monoclonal antibody that inhibits the receptor for CGRP, is being investigated for the prophylaxis of migraine. Phase 3 studies in episodic migraine, and a phase 2 study in chronic migraine, are ongoing. The drug is being jointly developed with Novartis.

Rosier says these treatments could hike costs. “The injectable medications, particularly, the CGRP inhibitors, have the potential to drastically increase drug costs for payers and patients,” she says. “These drugs will be considered specialty drugs with significantly higher price tags compared to the current, older agents used today. The good news is that these drugs can have a positive impact on medical, absence, and disability costs and improved productivity.”

Other notable pipeline treatments include:

• Dihydroergotamine mesylate inhalation(Semprana, Allergan). Shown to be effective in both early and late-phases of migraine headaches, while triptans are generally most effective for treating the early phases. 
• Lasmiditan (COL-144, CoLucid Pharmaceuticals). A member of a novel drug class called “ditans,” which penetrates the central nervous system and selectively targets 5-HT1F receptors expressed in the trigeminal nerve pathway, believed to play a key role in migraine attacks. 

Finally, Trigemina is conducting a phase 2 study of TI-001 (intranasal oxytocin) for the treatment of chronic migraine.

Next: Other options

Other options

Ambres points out that some treatments are not pharmacologic. For example, according to a recent study in BMJ Open, 12 acupuncture sessions were found to reduce at least half of the migraine attacks in 51% of patients with moderate or severe migraines.

FDA has approved a few devices to treat migraines, including Cefaly in 2014, which uses an electrical shock that targets the trigeminal nerve, which is associated with seizure control, and eNeura’s transcranial magnetic stimulator. 

More than 720 clinical trials are undergoing or completed for the treatment of migraine headaches, according to the U.S. National Institutes of Health’s registry of clinical trials. These studies range from new medications and devices, combinations of existing medications, varying treatment approaches, and lifestyle changes. 

Health plans need to take into account overall treatment costs, as they consider acupuncture or other non-pharmacologic modalities, which can be much more cost effective, according to Ambres.

Payer implications

For some payers, migraine drugs continue to rank in the top 50 drugs (by cost) in their pharmacy benefit, according to Rosier.

To address the drug-specific costs associated with these pharmaceuticals, some payers have implemented utilization management approaches such as quantity and dosing limitations, prior authorization and step therapy approaches, she says. “These programs are intended to ensure the drugs are used for the clinically appropriate purpose of treating migraines and that when lower cost products are available, such as generics, they are used as initial, first-line treatment at the right dosage.”

Tracey Walker is content manager for Managed Healthcare Executive.