By Lisa Seachrist
WASHINGTON - The FDA granted accelerated approval for Ontak, a fusion protein therapy for the treatment of persistent or recurrent cutaneous T-cell lymphoma (CTCL) developed by Seragen Inc., of Hopkinton, Mass., a wholly-owned subsidiary of Ligand Pharmaceuticals Inc.
"That's two in one week, and we are just delighted," said Paul Maier, Ligand's senior vice president and chief financial officer. Ontak, manufactured by Seragen and distributed by Ligand, will be available to patients in another week. Ligand bought Seragen in a $67 million deal last year, and rights to Ontak were included in that agreement.
On Feb. 2, the FDA approved Ligand's topical therapy for Kaposi's sarcoma, Panretin gel.
Under the accelerated approval process, Ligand is required to conduct post-approval clinical trials of Ontank to further document safety, efficacy and pharmacokinetic profile.
Ontak, or DAB389IL-2, is a diphtheria toxin fragment A-fragment B, genetically fused to human interleukin-2 (IL-2) through amino acid 389 on the toxin chain. The construct targets high-affinity IL-2 receptors on activated T lymphocytes. Once bound, it enters the cell, where fragment A of the toxin inhibits protein synthesis and kills the cell.
CTCL is a disfiguring form of non-Hodgkin's lymphoma (NHL) that manifests initially in the skin, causing itching and susceptibility to infection. The prognosis for CTCL depends on the stage at which the cancer is identified. Early-stage CTCL has a median survival of 10 years. Late-stage disease has a median survival of three years.
Ontak's U.S.-Europe Potential Pegged At $50M A Year
Approximately 16,000 patients in the U.S. have CTCL. Between 800 and 1,000 cases identified each year. The company estimates the market potential for Ontak in the U.S. and Europe at $50 million per year.
The cost for Ontak will run between $25,000 and $50,000 per year depending on the dose selected and the number of cycles administered. Current therapies cost anywhere between $5,000 to $60,000 per year.
"None of the drug therapies offered to treat CTCL have been approved by FDA," Maier said. "With Ontak, physicians now have a product that will provide a proven alternative."
Ontak's approval triggered milestone payments to Eli Lilly and Co., of Indianapolis, Seragen common shareholders and SmallPharma LLC, of Hopkinton, Mass., from whom Ligand purchased the multi-product contract manufacturing and development facilities for the manufacture of Ontak and other products.
With the development of Targretin's gel and oral formulations, Ligand could eventually have products to treat all stages of CTCL. The company intends to file new drug applications for both Targretin formulations in 1999.
In addition, Ligand is looking to develop Ontak for more common forms of NHL based on promising results from preliminary clinical studies.
"Our strategy has always been to build a strong oncology presence," Maier said. "We start with a niche product that can more easily make it through the approval process and, as the drugs declare themselves useful in other indications, we will work for our follow-on registrations."
Ligand disclosed the FDA approval after the stock market closed Friday. The company's shares (NASDAQ:LGND) ended the day at $12.25, unchanged.
The FDA also approved Minneapolis-based Orphan Medical Inc.'s Busulfex (busulfan) Injection for use as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia.
An oral form of busulfan is currently used in bone-marrow transplants, but treatment requires an already-nauseated patient to take a large number of pills. The intravenous form of busulfan avoids that pitfall. An FDA advisory panel gave its recommendation to the product last month. (See BioWorld Today, Jan. 14, 1999, p. 1.)
Orphan Medica's stock (NASDAQ:ORPH) closed Friday at $7.812, up $0.062.