BETHESDA, MD 29 August 2013—Caring for patients with rare diseases is all in a day's work for Jeanine Utz, adjunct assistant professor of experimental and clinical pharmacology at the University of Minnesota, Fairview, in Minneapolis.
Utz is a researcher and clinician specializing in the care of patients with lysosomal storage diseases. She is also part of the patient care team at the phenylketonuria clinic at the University of Minnesota Medical Center, Fairview.
"It is a very exciting area to work in," Utz said. "It's an area where we can really stake a claim and literally help the world understand what a pharmacist can bring to the clinical picture of patient care."
Some 50 lysosomal storage disorders have been identified, and they affect about 1 in 5000 births, according to the National Institutes of Health. In general, the diseases may result in multisystemic dysfunction, neurologic deterioration, and early death.
Among this group of diseases, "there are only 6 that have an FDA-approved drug therapy," Utz said.
Those disorders—Fabry disease, Pompe disease, Gaucher disease, and mucopolysaccharidosis types 1, 2, and 6—can be treated with FDA-approved i.v. enzyme replacement products. One FDA-approved oral therapy is available for the treatment of Gaucher disease, and other therapies are being investigated.
Utz said that although she doesn't work in the hospital's pharmacies, she helps them navigate risk evaluation and mitigation strategy programs and prior authorization procedures for orphan drugs. She also helps to obtain federal 340B prices for the drugs whenever possible.
"These drugs are so expensive, and pharmacies, revenuewise, may just be breaking even, depending on how the reimbursement goes," she said.
For patients with rare diseases in general, she said, "the landscape there is changing a little bit" as more drugs are approved.
"All of the sudden, the landscape has competition," Utz said. "It is a new thing for people to have to deal with."
People with type 1 Gaucher disease, for example, have had three FDA-approved enzyme-replacement therapies available as options since mid-2012.
Some of that competition is likely the result of federal incentives for the development of orphan drugs. Companies seek orphan-drug designation because it can confer substantial tax benefits that reduce the cost of developing new drugs.
An FDA database in early August contained more than 2800 records of orphan drug designations granted by the agency since 1983, when the Orphan Drug Act was signed into law.
FDA on June 12 published a final rule on orphan drug regulations that is intended to clarify for manufacturers the agency's criteria for granting orphan drug designation.
The rule doesn't directly affect pharmacy practice, said James Cloyd, director of the Center for Orphan Drug Research at the University of Minnesota College of Pharmacy in Minneapolis.
"But what does affect practice are things like, should orphan drugs be on formulary, and how should they be managed?" Cloyd said.
According to FDA, orphan therapies for rare diseases—those that affect less than 200,000 Americans—are the fastest-growing segment of drug development. The agency stated that about a third of the new molecular entities approved by FDA over the past five years have been orphan drugs.
Although each rare disease affects a small number of patients, rare diseases as a whole affect about 30 million Americans, according to federal estimates.
Cloyd said that most pharmacists, over a period of years, will "undoubtedly" interact with a patient or family in which someone has a rare disease. He said this is even more likely in health-system pharmacy practice.
He said few pharmacists and physicians "can speak, off-the-cuff, knowledgeably, about a rare disease, because they are uncommon and they're not typically diagnosed or managed in a primary care or even secondary or tertiary care setting."
But he urged pharmacists to have a working knowledge about the existence of rare diseases and how they are managed.
"For those rare disorders for which there are drug treatments, there are several kinds. There are FDA-approved products. Some of them are injectables, some are orals," he said. "There is an extensive off-label use, and when a pharmacist in a community practice interacts with a family member or a patient in that situation, the first response should be, 'How can I help?' as opposed to, 'I don't know anything about this.'"
Orphan drugs include some of the highest-priced therapies, sometimes retailing for several hundred thousand dollars for a year's worth of treatment.
"These drugs work," Cloyd said. "And as a result, individuals with rare disorders who have a shortened lifespan now are living longer, so the cost on an individual basis is significant. And as the number of these medications increases, health-system pharmacists will need to look at ways to make sure the drugs are used safely, and effectively, and economically."
But not all orphan drugs are new and costly.
For example, acetylcysteine received orphan drug designation five times between 1987 and 2012. Only one use—intravenous administration for the prevention of acetaminophen–induced liver injury—is currently described in the labeling for this product, sold as Acetadote.
In addition to the i.v. formulation, acetylcysteine is marketed as an oral inhalation solution and as a dietary supplement. Various formulations of the drug are also being investigated in clinical trials for the treatment of a wide range of conditions, some of them rare.
Cloyd called the use of acetylcysteine "an example of . . . where pharmacists can play an important role in helping other clinicians make good decisions about therapy."
"Some pharmacies will sell dietary supplements, and some hospital pharmacies will have all three products, conceivably," he said. "When would you use N-acetylcysteine i.v. for off-label uses, and should you? How about the [inhalation solution], and what about the dietary supplements?"
The June 12 final rule clarified FDA's criteria for determining when marketing exclusivity applies to orphan drugs. FDA said the rule also prevents manufacturers from defining artificial "orphan subsets" of patients who have a nonrare disease and seeking orphan designation for drugs to treat those patients.
The final rule states that drug companies need not conduct a clinical trial to support a claim that an orphan drug candidate is clinically superior to a different marketed version of the drug and thereby eligible for orphan designation.
"That's huge," Cloyd said, noting that clinical trials are expensive for manufacturers to conduct.
Cloyd was involved in the development of rectally administered diazepam for the treatment of recurrent seizures in certain patients with epilepsy, a use that earned an orphan designation for the drug in 1992.
But he said caregivers were reluctant to administer the drug through this route because of "social objections or legal objections."
FDA in 2012 granted an orphan designation to an intranasal formulation of diazepam and this year approved an orphan designation for the drug when delivered through an autoinjector. Both orphan designations are indicated for the control of increased seizure activity in patients with epilepsy, and FDA did not require the manufacturers to prove clinical superiority by conducting clinical trials of the delivery systems.
"By and large, the final rule, in my estimation, largely makes things clearer to drug manufacturers" and makes it "somewhat easier to get orphan designation," Cloyd said.