By Lisa Seachrist
Xoma Corp.'s stock fell 25 percent Tuesday on news the FDA didn't think the company had sufficient data to file a biologics license application (BLA) for its lead product, Neuprex (rBPI21), as a treatment for severe meningococcemia.
Xoma's stock (NASDAQ:XOMA) closed at $4.03, down $1.343, after the company reported the agency failed to give the go-ahead for Neuprex's BLA following a meeting with FDA discussing the results of a Phase III study of Neuprex. Xoma will continue to work with the agency to find a way of getting Neuprex approval in meningococcemia.
"It's disappointing," said Peter Davis, chief financial officer of Berkeley, Calif.-based Xoma. "We believe FDA thinks our data is positive and supportive, but they didn't think it was strong enough to go forward. We still believe in this product, as does Baxter, and we are looking at all possible ways to move Neuprex forward. However, we think that should be a private conversation with FDA."
In January, Baxter Healthcare Corp., of Deerfield, Ill., acquired worldwide rights to Neuprex for the treatment of meningococcemia in a deal that garnered Xoma $35 million in up-front and milestone payment plus any royalties on future sales. Davis said Baxter remains supportive of Neuprex as a treatment for meningococcemia. In addition, Baxter and Xoma have begun to look at additional indications for Neuprex, but the companies aren't releasing the exact indications until they make the decision to move forward. (See BioWorld Today, Jan. 26, 2000, p. 1.)
The companies discussed with FDA the adequacy of the pivotal Phase III study of the drug to support a BLA for meningococcemia. That study, which was a placebo-controlled, double-blinded, randomized clinical trial, included 395 patients and showed Neuprex reduced mortality and limb loss as a result of meningococcemia. Xoma has yet to publicly release the data from the study, but Davis said the company intends to publish the study soon in a peer-reviewed journal.
"The data haven't yet been laid out for us to see," said Richard Stover, senior analyst with Arnhold and S. Bleichroeder Inc. in New York. "But the company has told us the drug causes reductions in mortality, reductions in limb loss and improvement in the overall neurological function. And, right now, there is nothing out there to treat this condition."
Meningococcemia is a blood-borne infection caused by Neisseria meningitidis. A seasonal infection, the disease is caused when the gram-negative bacteria enter the bloodstream where they and their endotoxins can prompt a systemic inflammatory response that leads to symptoms ranging from flu-like symptoms to shock, organ failure and death - often within hours. Survivors often suffer from gangrene followed by amputation and/or central nervous system damage.
Because the symptoms progress so rapidly, any trial testing a drug in this relatively rare indication must be administered within hours of a patient entering the hospital. Stover noted the need for such prompt enrollment into a study means conducting a clinical trial in meningococcemia may not provide the robust statistics FDA is accustomed to reviewing.
"It's clear from the nature of the disease, a study in meningococcemia is unlikely to generate the kind of 'p' values FDA likes to see," Stover said. "That means there are a lot of little kids are going to die and a lot of limbs on the cutting room floor because of 'p' values. Should this drug be withheld because of that?"
Neuprex, a part of the Xoma's BPI technology, is derived from the bactericidal/permeability protein found in white blood cells. The drug works by poking holes in the outer shell of bacteria and killing them. In addition, it binds bacterial endotoxin, neutralizing its biologic activity and accelerating its clearance from the bloodstream.
In September, Xoma announced it had stopped a Phase III clinical trial early when Neuprex failed to prevent infection in patients who had undergone hemorrhagic trauma. (See BioWorld Today, Sept. 28, 1999, p. 1.)
In addition to Neuprex, Xoma, in partnership with South San Francisco-based Genentech Inc., is developing a humanized antibody engineered to block the CD11a receptor on T cells in order to inhibit their activation and migration. That product, anti-CD11a, is being studied in two Phase III studies of psoriasis. The companies also are testing the drug in a Phase I/II study.
In collaboration with Irvine, Calif.-based Allergan Inc., Xoma is developing a topical BPI in combination with an antibiotic for the treatment of eye infection.
Xoma is looking for partners for its Mycoprex antifungal program and is advancing the development of BPI-derived antiangiogenic compounds that may be useful in treating retinal diseases, tumors and inflammatory diseases. Finally, Xoma is looking for partners for its Genimune product, an antibody-based targeting component fused with gelonin, a proprietary cytotoxin. Medical targets are T- and B-cell-mediated autoimmune diseases and immune system cancers.