By Lisa Seachrist
WASHINGTON — Under procedural changes instituted as a result of FDA reform, the agency told Seragen Inc. the review of Ontak for treatment of persistent cutaneous T cell lymphoma (CTCL) is complete and summarized actions the company must take to secure approval.
The "Complete Review" letter replaces the approvable and non-approvable letters that the Center For Biologics Evaluation and Research used previously. By issuing the letter, the FDA stopped the review clock until the Hopkinton, Mass.-based company addresses concerns in the biologics license application (BLA).
While not detailing the steps which need to be taken, Seragen said the FDA identified deficiencies in safety, efficacy, manufacturing and product characterization.
"We are trying to be very conservative and careful about the letter," said Jean Nichols, Seragen's president and chief technology officer. "I can tell you that they have not asked for new clinical trials and we should be able to provide the information that they need in a matter weeks, not months."
Nichols told BioWorld Today that not only was Seragen expecting the letter, none of the issues raised by the agency came as a surprise. Seragen will need to provide additional data and in some instances use different methodology to analyze data.
"We expected to get the letter. The agency pushed very hard to meet the [six month] deadline for priority review," Nichols said. "We had been talking to the agency before the letter and our interactions with the agency continue to be productive. I am very positive about seeing Ontak through the process."
Ontak, which is diphtheria toxin fragment A-fragment B fused to human interleukin-2, targets high affinity IL-2 receptors on activated T lymphocytes. CTCL cells express these receptors in abundance. Once bound, it enters the cell, where fragment A of the toxin inhibits protein synthesis and kills the cell.
Ontak served as the basis for Seragen's announced merger with Ligand Pharmaceuticals, Inc., of San Diego, which is expected to be complete by the end of this year. (See BioWorld Today, May 12, 1998, p. 1.) After the merger, Ligand will possess therapies for early-stage CTCL with its own oral and topical versions of Targretin and late-stage CTCL with Ontak.
"The letter was expected from the FDA," said Susan Atkins, spokeswoman for Ligand. "It in no way changes the deal with Seragen or the plans for the [CTCL] program."
CTCL is a disfiguring from of non-Hodgkin's lymphoma that manifests initially in the skin, causing itching and susceptibility to infection. Approximately 800 patients are diagnosed with the disease each year in the U.S. As the disease progresses over 10 to 20 years, it can affect other organs; the median survival for late-stage patients is less than three years.
On June 2, the Oncologic Drugs Advisory Committee agreed unanimously that Ontak offered an acceptable toxicity profile and enough clinical benefit to patients to recommend the FDA grant the drug accelerated approval.
Seragen's stock (OTC Bulletin Board:SRGN) closed at $0.52 down $0.05. Ligand's stock (NASDAQ:LGND) closed Thursday at $12.687 down $0.812. *