By Lisa Seachrist
WASHINGTON ¿ Following the crushing disappointment of a Phase III failure last July, Alfacell Corp. said its lead drug candidate, Onconase, provided a survival benefit in a Phase II study of the drug as a treatment for malignant mesothelioma.
The multicenter study showed that Onconase treatment provided a 34.3 percent one-year survival rate and a 21.1 percent two-year survival rate to patients with inoperable malignant mesothelioma. The Bloomfield, N.J.-based company expects to have preliminary results from a Phase III study of the drug comparing it to the standard chemotherapy agent, doxorubicin, later this year.
¿An overall 21 percent two-year survival rate is very respectable in this disease,¿ said Gail Fraser, chief financial officer at Alfacell. ¿We are looking forward to completing the Phase III study.¿
Malignant mesothelioma is a cancer of the lining of the lungs and abdomen. This cancer is associated with asbestos exposures and develops 10 to 20 years after the exposure. The vast majority of patients diagnosed with inoperable malignant mesothelioma die within a year of diagnosis. The disease strikes approximately 3,500 Americans every year.
Fraser noted that the cancer usually begins in the lining of the lungs and spreads to the abdominal lining. A patient¿s prognosis worsens when the abdominal lining is affected.
¿Most patients present at the doctor¿s office with cancer that can¿t be treated with surgery,¿ Fraser said.
Onconase is an Rnase ¿ an enzyme that degrades RNA ¿ derived from purified frog eggs. It works by destroying the RNA transcripts a cell creates in order to produce protein and energy. Alfacell has conducted some in vitro studies indicating that normal cells may have the wherewithal to keep the drug in check, whereas tumor cells are susceptible to Onconase.
The company tested Onconase in 105 patients with inoperable malignant mesothelioma. All patients received a once-weekly infusion of Onconase until their cancers failed to respond to the drug. Thirty-nine percent of the patients demonstrated evidence of clinical activity either by showing a reduction of tumor size or stabilization of disease as measured by a CAT scan.
For patients who demonstrated clinical activity, the mean survival time was 17.1 months, with a one-year survival rate of 61 percent and a two-year survival rate of 31.7 percent. Patients with the negative prognostic indicator of abdominal involvement had a mean survival rate of 12 months, with a one-year survival rate of 48 percent and a two-year survival rate of 35.6 percent.
Patients with an epitheliod histology in their tumors had a mean survival time of 9.6 months, with a one-year survival rate of 42 percent and a two-year survival rate of 25.7 percent.
¿We don¿t know why patients with abdominal involvement did better than patients without abdominal involvement in this study,¿ Fraser said. ¿We¿ll be looking at the Phase III study for more information.¿
Patients generally tolerated Onconase well, with only five dropping out of the trial as a result of side effects that included renal problems, edema and anaphalactoid rash.
Because there is no FDA-approved and accepted way of treating malignant mesothelioma, the agency told the company that for its Phase III study it could choose a chemotherapeutic agent to test Onconase against. After consultation with experts in mesothelioma, Fraser said the company chose doxorubicin because many oncologists use that drug as a single-agent therapy.
¿Once we have the preliminary Phase III data in hand, we will request a pre-NDA meeting with the agency to see if they will accept the data,¿ Fraser said.
The company expects to have the preliminary Phase III data in September and hopes to attain fast-track status for the drug once the NDA has been filed.
Last July, Onconase failed to show a survival benefit in patients with pancreatic cancer, and the company decided to stop developing the drug for that indication and focus on the mesothelioma indication. The company also is developing the drug as a treatment for breast cancer and non-small-cell lung cancer. (See BioWorld Today July, 16, 1998, p. 1.)
Alfacell¿s stock (NASDAQ:ACEL) closed up 6.25 cents per share Tuesday, at 43.75 cents.