Slide 1

Now orphan drugs. Orphan drugs are a category or a mechanism to encourage and facilitate the development of drugs for rare diseases or conditions.

Slide 3

Now, a rare disease or a condition is a disease or condition that affects less than 200,000 persons in the United States or can affect more than 200,000 persons but for which there is no reasonable expectation that the cost of developing and making available in the US a drug for such a disease or condition will be recovered from sales in the United States.

When one applies for orphan drug on status, one applies for what is called orphan drug designation. First, you need to go to the agency and submit an application and request a designation that your product is indeed a rare disease or a product for a rare disease or condition.

This program is administered by the Office of Orphaned Products Development, which in the Office of the Commissioner. This group is involved in the identification of orphaned products, the facilitation of the development, and it also administers the orphan drug, a program.

However, the scientific review and medical review of these products are conducted in the scientific and medical review centers of the FDA. So, the Center for Drugs Evaluation Research and the Center for Biologics Evaluation and Research will conduct these reviews.

However, the centers do work closely with the Office of Orphan Products. As this office is in the Commissioner’s Office, there is a lot of oversight of this program by the Commissioner.

Now, these studies, the clinical studies for these products are going to be very small patient population wise just because there are not a lot of people with the disease or condition that you’re studying. Even though the number of patients in these studies, and I’ve seen approval of some of these drugs where you have 30 patients, even though you do have a small number of patients, the studies that you conduct still need to be adequate and well-controlled. You can imagine from a statistical perspective how difficult that can be. It’s wonderful that this program is in place for orphan drugs and there’s a lot of success stories and a lot of sponsors and applicants try to take this route whenever possible. But it is challenging. It is challenging because the patient numbers are so small, and powering a study to demonstrate efficacy can be quite challenging.

Slide 4

Here are the incentives for development of drugs for rare diseases and conditions. One of the incentives is seven years of marketing exclusivity once the product is approved. During this seven year period, FDA will not approve the same drug for the same disease or same condition. As the product that’s received orphan drug, a designation. The seven years of marketing exclusivity begins on the date of approval and it is only for the indication for which the drug has been approved. Another application could be approved for the same drug in a different indication. Tax credits are another incentive for orphan drug development and these are tax credits for clinical research to generate data required for marketing approval of that indication. The FDA grants formal protocol assistance. The agency will assist the sponsor in coming to agreement and providing input on clinical protocols, which is more guidance than one usually receives from the agency.

The agency also has research grants available to give to sponsors who are developing these products and these grants run from $200,000 per year for a phase one study to $350,000 per year for phase two and phase three studies. These research grants are … they go up to three years in length. The agency also provides written recommendations on the pre-clinical and clinical investigations. Now, according to the agency, this assistance that the agency gives sponsors usually results in decreased development time.

Slide 5

Now if someone has an approved orphan drug and another company has developed a drug that is clinically superior to that orphan drug this superior drug can break orphan drug exclusivity. So it can break the seven year marketing exclusivity period that this orphan drug has. So you can have the same drug for the same indication as a previously designated product, but if that product is clinically superior then the seven year marketing exclusivity will be broken and that is to ensure that patients will benefit from this clinically superior drug.

Now, clinical superiority can be demonstrated in one of three ways. One is greater effectiveness as assessed by an effect on a clinically meaningful endpoint in adequate and well-controlled studies. So one would need to do a head-to-head study of the currently marketed product against this investigational drug to determine clinical superiority that way.

Clinical superiority can also be a demonstration of greater safety in a substantial portion of the target population. And then once again that’s a head-to-head study looking at safety parameters.

And the last is a demonstration that the drug makes a major contribution to patient care. An example of this would be if someone has a product that is given by IV infusion once a week and another company comes along and develops the same product that can be taken as a pill. That’s obviously a major contribution to patient care.