FDA Approves First Sublingual Allergy Immunotherapy Agents

In April, the U.S. Food and Drug Administration (FDA) approved three sublingual oral immunotherapy (SLIT) agents, the first to be approved in the United States.

Oralair, from GREER Laboratories, which is indicated for grass pollen-induced allergic rhinitis with or without conjunctivitis confirmed by positive skin test or in vitro testing for grass pollen-specific immunoglobulin E antibodies for any of five grass species (Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue grasses), received FDA approval on April 1 of this year. Two weeks later, the FDA approved Merck’s Grastek, which treats those allergic to Timothy grass. And, just three days later, the FDA gave the go-ahead to Merck’s Ragwitek, a treatment for ragweed allergies.

These three medications are the first FDA-approved allergy treatments to be administered sublingually to help desensitize a patient to a particular allergen or group of allergens. In the U.S., an estimated 7.5 million people are allergic to Timothy and other grass pollens, while approximately 4.5 million people are allergic to short ragweed pollen.

How They Work

“This is a revolutionary change in the way the patient undergoes desensitization to allergens by providing immunotherapy, yet the effects of providing it appear to be essentially the same as injection therapy,” said Bradley Marple, MD, professor and vice chairman of the department of otolaryngology-head and neck surgery and an associate dean for graduate medical education at the University of Texas Southwestern Medical Center in Dallas. Dr. Marple is also a member of ENTtoday’s editorial advisory board.

Historically, allergy treatment has been a three-tiered process, said Dr. Marple. The first tier involves avoiding the allergen altogether, though some, like pollen, can be hard to hide from as the spring season unfolds. The second tier involves the use of nasal steroids, nasal irrigation, and antihistamines. If allergy symptoms persist, immunotherapy is recommended. “This translates into patients needing to be somewhat tethered to a physician’s office, and it’s kind of a hardship for patients who live removed from the office and who have busy schedules,” said Dr. Marple.

There’s also the fear factor. “Many patients do not pursue immunotherapy because some patients don’t like needles and are scared of shots,” said Nathan Sautter, MD, an assistant professor of otolaryngology at Oregon Health and Science University in Portland.

But with oral immunotherapy, the antigens are absorbed through the mucosa and then migrate through the lymphatic system and into the lymph nodes, where they works with the immune system to help desensitize the body to an allergen, said Dr. Marple. The patient only needs to be observed for potential anaphylaxis after the first pill is taken; if there’s no reaction, the patient can self-administer at home for the remainder of the treatment. The regimen typically starts 12 to 16 weeks before the grass/ragweed season begins and may continue for up to three years.

While this form of immunotherapy is new to the United States, it has been used safely in Europe for about two decades, said Dr. Sautter. Some physicians in the U.S. have also used allergy serums sublingually through off-label prescription. “The advantage of having FDA approval for these tablets means the patient receives the same dose of the medication every time in a form that is more effectively absorbed under the tongue,” he said.

The risk of anaphylaxis and throat swelling is decreased with oral immunotherapy compared with injections, which is why patients can move out of the physician’s office after the first treatment; however, all patients on oral immunotherapy are advised to have a readily accessible dose of an auto-injectable epinephrine in case a problem occurs away from the physician’s office.

Who Benefits

“For people who have more persistent seasonal allergic rhinitis but who haven’t tried injection therapy, these medications are likely to become a new form of treating allergies without shots,” said Dr. Marple. Oralair is approved for patients as young as five years old, and Grastek is approved for those aged 10 and older. “It’s ideal for pediatric patients, because children are really not big fans of having an injection every one to two weeks,” said Dr. Marple.

But not all patients benefit from oral immunotherapy, said Dr. Sautter. “What I’ve seen estimated is up to an average of 30% reduction in allergic symptoms in every patient,” he said. “Some people will derive more benefits and some will derive less. In some patients, allergy symptoms will go away completely.”

Oral immunotherapy is not recommended for patients with severe, unstable, or uncontrolled asthma, those who may have certain underlying medical conditions that are not compatible with severe allergic reactions, those who may be allergic to the ingredients in the medication itself, or those who are on beta blockers, which can interact poorly with oral immunotherapy.

What Otolaryngologists Need to Know

Physicians who treat patients with grass or ragweed allergies should know that there’s an alternative to allergy shots, said Linda Cox, MD, the immediate past president of the American Academy of Allergy, Asthma and Immunology. “As far as we know, serious side effects are rare, and from a positive standpoint, patients have a new way to treat seasonal allergy.”

The cost to patients for allergy treatments varies with the number of allergies being treated as well as the frequency with which the shots are given, but Dr. Sautter said that a good estimate for one month of allergy shots is approximately $75. Citing a Merck press release, Dr. Sautter added that the cost of one Grastek or Ragwitek pill is $8, or $240 for a one-month supply.

“A good estimate is that sublingual tablets are about three times more expensive than shots,” said Dr. Sautter. “In this case, you are paying for the ‘convenience factor’ as well as the fact that it is a new drug, and I would expect cost to decrease over time as more sublingual tablets enter the market.”

---

Cheryl Alkon is a freelance medical writer based in Massachusetts.