Rare Disease Treatments: Orphans' Saving Lives : Part 3

by Food and Drug Administration (FDA)

(Page 3 of 3)

Direct enzyme therapy, to replace enzymes that the body cannot produce because of a genetic defect, has several problems. Since enzymes are proteins, they must be injected, rather than taken orally. Most enzymes remain in the blood only a short time, requiring frequent injections, which in turn can cause the development of antibodies that clear the enzyme from the blood even more frequently. In time, serious allergic reactions can occur.

Working with Frank Davis, Ph.D., Abuchowski developed a process called PEGnology, in which strands of polyethylene glycol, a nontoxic polymer already approved by FDA for use in food, cosmetics and other drugs, are attached to the surface of the enzyme, "camouflaging it from the immune system. As a result the body does not recognize the injected enzyme as foreign and does not produce antibodies that would remove it from the blood," according to the company literature. "This reduces the number of injections needed to achieve therapeutic blood levels in addition to reducing allergic reactions."

"PEG-ADA, from a purely business and financial sense, might not have been the best product to select, but it really was done for other reasons," said Donna Chappina, a spokeswoman for Enzon, the company Abuchowski and Davis formed to develop the drug. "They felt it was the most difficult one to accomplish. It was purely a scientific venture, two scientists banging their heads together."

Severe combined immunodeficiency was also a disease that had received little attention, because its patient population was so small, perhaps 40 cases known worldwide. When clinical testing began on the product, 14 patients in the United States and Europe were included in the drug trial, patients who until that day had no hope of escaping frequent injections and the effects of the disease. All showed improvement within 6 to 12 months, according to Chappina.

Although the cost of PEG-ADA therapy is almost $60,000 a year and the patients are responsible for the cost, Enzon has worked with the insurance companies covering families of patients and believes in most cases the cost will be covered, Chappina said. "The cost of the drug really has to do with the very high cost of the native enzyme, bovine adenosine deaminase, and, because there are only 14 people receiving the drug, we can't spread the cost out," Chappina said.

Enzon also has hopes for other PEGnology drugs, in various stages in the development process, that might serve wider audiences, Chappina said. In the meantime, there are other, nonfinancial rewards.

The families of six patients were flown into New Jersey for a press conference when PEG-ADA's license approval was announced earlier this year. The morning after their arrival, they all went up to Abuchowski's table in the hotel restaurant, many with tears in their eyes, to thank him for giving their children a better life.

That is the promise that the Orphan Drug Act holds out to people throughout the country who have a variety of rare diseases. No longer is a disorder that might afflict only a dozen people ignored by medical product manufacturers because the research is economically unfeasible. Now those sufferers have a chance that somehow, somewhere, a cure or a treatment will be found.

History of the Orphan Drug Act

FDA set up the Office of Orphan Product Development in 1982 to focus on drugs, medical devices, foods for medical purposes, and biologics such as immune globulin for rare disorders. President Reagan signed the Orphan Drug Act into law on Jan. 3, 1983. It guarantees the developer of an orphan drug seven years of market exclusivity and 50 percent tax credit for certain clinical research expenses. Initially, the act applied only to patient populations when it could be shown there was little hope of recovering development costs from sales in the United States. A later amendment to the act defined an orphan product as one with a potential patient population of fewer than 200,000 people.

Under the Orphan Drug Act, FDA makes grants for drug development, assists the drug developer in designing the clinical studies required for marketing, and can speed up the drug approval process.

"There are no real shortcuts," said Marlene Haffner, M.D., FDA's director of Orphan Product Development. "A lot of these drugs are for very serious and life-threatening disorders, in some cases affecting only a few hundred people. You have the smaller NDA [new drug application] and a group of very needy people, and that's what expedites it. But the safety and efficacy requirements are the same."

Since enactment of the Orphan Drug Act, 41 drugs for rare diseases have been developed and brought onto the market. Activity in orphan products — which, in addition to drugs, can include biologics, medical devices, and foods marketed for medical purposes — is reaching an all-time high. According to Haffner, FDA has designated as orphans 375 drugs, and at least 150 are being actively developed or are going through the approval process. The federal monies available to fund orphan drug development have increased steadily — from $500,000 in 1983 to $7.5 million in 1990.

The term "orphan drug" refers to a drug that will serve so few patients that it will be commercially impractical for a manufacturer to sponsor it. Orphan drug also refers to compounds in the public domain for which there can be no patent protection once a company goes through expensive efficacy tests and gets FDA approval, so that a competitor could immediately begin producing a generic copy at a fraction of the cost. The phrase was coined in a 1968 editorial in the American Journal of Hospital Pharmacy, "Homeless or Orphan Drugs."

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FDA is A United States government body that oversees medical devices, including contact lenses, intraocular lenses, excimer lasers and eyedrops. In the US, these products must be approved by the FDA before they can be marketed.