A quick scan through the drug pipelines of many biotechnology and pharmaceutical companies will reveal a significant number of drugs under development that have received "orphan drug status." Yet, it wasn't all that long ago that orphan drugs were considered too small to devote valuable R&D resources. As a consequence they did not feature prominently on the product development radar screens of either pharma or biotech companies.

However, that situation has changed in a hurry. Small patient populations have suddenly become big business for biotechnology and pharmaceutical companies alike. The pipeline is rapidly filling with candidate medicines targeting rare and ultra-rare diseases. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), last year biopharmaceutical research companies had approximately 460 medicines targeting rare diseases either in clinical trials or awaiting FDA review. (See BioWorld Insight, Oct. 15, 2012.)

That total now has grown to well over 500 medicines. Since the beginning of the year the FDA Office of Orphan Drug Products has granted 69 compounds orphan drug designation (ODD), with drugs intended to treat rare diseases or conditions affecting fewer than 200,000 people in the U.S. That designation confers special incentives to the drug developer, including tax credits toward the cost of clinical trials, prescription drug user fee waivers and may entitle a period of seven years U.S market exclusivity upon FDA approval.

One of the latest products to receive ODD is XEN402 from Xenon Pharmaceuticals Inc., of Burnaby, British Columbia, and Teva Pharmaceutical Industries Ltd., of Jerusalem. XEN402 is being developed to treat pain associated with erythromelalgia, a rare autosomal dominant condition characterized by burning pain in the feet and hands. XEN402 inhibits the SCN9A sodium channel. (See BioWorld Today, April 24, 2013.)

Among the other products to receive ODD this year include: P140K methylguanine methyltransferase (MGMT) transduced human CD34 cells (LG631-CD34) for bone marrow protection in the treatment of glioblastoma multiforme being developed by Lentigen Corp., of Gaithersburg, Md. LG631-CD34 consists of patients' adult hematopoietic stem cells genetically modified with a lentiviral vector expressing a human MGMT gene variant, which is designed to protect the cells from the toxic side effects of Temodar (temozolomide, Merck & Co. Inc.), a standard-of-care treatment for glioblastoma multiforme. LG631-CD34 is currently being evaluated in a Phase I trial. (See BioWorld Today, Feb. 4, 2013.)

La Jolla Pharmaceutical Co., of San Diego, received FDA orphan designation for LJPC-6417 for fibrodysplasia ossificans progressiva (FOP). LPJPC-6417 is a kinase inhibitor designed to target the bone morphogenetic protein type-1 receptor, which is mutated in FOP.

Accelerating Pace

Interest in drug development targeting orphan disease indications continues to build at an accelerating pace. This surge in R&D on orphan drugs is fueling a rapid growth in the worldwide orphan drug market, which is estimated to hit $127 billion by 2018, accounting for nearly 16 percent of total prescription drug sales. Those data were released in a new 2013 Orphan Drug Report from Evaluate at the BIO 2013 International Convention in Chicago last week.

That report sheds interesting light on the market dynamics of biopharmaceutical products aimed at rare diseases – projecting that sales will experience a compound annual growth rate of 7.4 percent between 2012 and 2018, nearly double that of the prescription drug market (excluding generics).

Last year alone orphan drug sales increased 7.1 percent to $83 billion from the previous year. That compares with a 2.1 percent decline in overall prescription drug sales (also excluding generics).

Kyprolis (carfilzomib), a drug targeting multiple myeloma from Onyx Pharmaceuticals Inc., of South San Francisco, was the most promising new orphan drug in 2012, and its U.S. sales are expected to reach $897 million in 2017.

Surprising Findings

"One of the surprising findings of the study's research was how quickly pharma has shifted efforts to more niche indications," Anthony Raeside, Evaluate's head of research, told BioWorld Insight.

In addition, the study found that orphan drugs that have been filed for regulatory review or are in Phase III trials provide a 1.7 times greater return on investment than non-orphan drugs, he added.

Market output also continues at a steady clip with approximately one-third of the new molecular entities approved by the FDA in the last five years having been drugs targeting rare diseases.

Orphans represented 35 percent of the total new drug approvals by the FDA in 2012, Evaluate noted in its findings.

The approval of orphan drugs is also off to a good start in 2013. In February, the FDA approved Pomalyst (pomalidomide, Celgene Corp.) to treat patients with multiple myeloma whose disease progressed after being treated with other cancer drugs.

Other key findings from the Evaluate report include the fact that the number of ODDs in the U.S. fell 7 percent in 2012, marking the first decline since 2007. Orphan designations in Europe, however, increased 44 percent, reversing a decline in 2011.

Among the pharma companies, the report found that Novartis AG, of Basel, Switzerland, will maintain its position as the world's top orphan drug company in 2018, with expected sales of $11.8 billion.

Of the orphan drugs in the pipeline, the report indicates that elotuzumab (AbbVie/Bristol-Myers Squibb Co.) indicated in multiple myeloma is the most valuable.