By Kim Coghill
Aronex Pharmaceuticals Inc.'s stock dropped 73 percent Monday after the FDA denied approval of the company's new drug application for Atragen, an injectable product for patients with acute promyelocytic leukemia (APL) who cannot take the oral formulation.
The bad news will force The Woodlands, Texas-based company to begin reducing its work force, which currently totals 85 people.
"I'm very anxious that the message gets out that the company continues to be in business and continues to progress its programs," said Geoffrey Cox, chairman and CEO of Aronex. "Clearly, what we are going to do is be very prudent concerning our cash at this juncture. We are in the process of reviewing the specific number of [labor reductions]. But the context in which that should be seen is that we want to make sure we keep our regulatory and clinical functions in place in order for us to be able to continue to address clinical and regulatory issues associated with the company's products."
Aronex's stock (NASDAQ:ARNX) closed Monday at $1.218, down $3.347.
The company will schedule a meeting with the FDA to determine where the problem lies with Atragen for APL. "We haven't had those conversations so I really can't comment," Cox said. "We believe strongly in the value of this product not only in APL, but we plan to move forward with this product in Europe where we have a less restrictive process with regard to the orphan drug."
Hoffmann-La Roche Inc., of Nutley, N.J., owns the orphan oral product, Vesanoid. The orphan status expires in November 2002.
Cox said preliminary comments from the FDA indicate that the product failed because Aronex didn't establish an identifiable population of patients. Aronex is not planning to conduct further clinical trials for the APL indication. "We want to focus our clinical program on the other indications where we have other market opportunities."
Atragen, a vitamin A derivative, is an injectable liposomal formulation of all-trans retinoic acid (tretinoin). Atragen is designed to work by inducing cell differentiation and, eventually apoptosis. It can be used in combination with chemotherapy regimens.
But Aronex believes non-Hodgkin's lymphoma will produce the largest market for the drug. "We see non-Hodgkin's lymphoma as a priority and we are in the process of planning to design further studies for non-Hodgkin's when we have the resources from a financial perspective," Cox said. Other than that, Atragen is being developed to potentially treat hormone-resistant prostate cancer (Phase II), renal cell carcinoma in combination with interferon-alpha (Phase I/II), and acute myelogenous leukemia (Phase II).
Monday's news didn't mark the first time Aronex has had a problem with APL for Atragen. Back in August 1999, the FDA said the Oncologic Drugs Advisory Committee would not review the drug due to deficiencies in the NDA, which was filed in December 1998. The company's stock suffered, dropping that day from $6.93 to $4.50, or 35 percent. (See BioWorld Today, Aug. 6, 1999.)
A month later, the FDA sent Aronex a letter detailing issues preventing approval. Mere publication of the letter sent Aronex's stock down another 20 percent as it closed at $3.68. (See BioWorld Today, Sept. 27, 1999.)
But Aronex continued working and in July 2000 amended its NDA to include additional safety and efficacy data in the proposed indication from patients enrolled in the clinical study after the 1998 NDA filing. In included data on 116 APL patients, whereas the original NDA included only 59 patients. (See BioWorld Today, July 7, 2000.)
Nyotran, another Aronex product, is an injectable liposomal formulation of nystatin for treating fungal infections. Last February, the drug failed to meet its primary endpoint in a Phase III study in patients with cryptococcal meningitis. In September, Aronex said results were positive in a Phase II trial in refractory or intolerant patients with invasive Aspergillus, in a comparative urinary pharmacokinetics and drug disposition study, in efficacy trials in the treatment of disseminated candidasis in guinea pigs and in a differential in vitro antifungal activity study. (See BioWorld Today, Feb. 17, 2000.)