Meeting its primary endpoint in a Phase III trial, Ceplene proved itself not only as a potential lifesaver for acute myeloid leukemia patients, but also as an immune modulator that can show benefit in different classes of cancer.

While Maxim Pharmaceuticals Inc. awaits an FDA ruling on its new drug application to use Ceplene in metastatic malignant melanoma patients, it now has the data it needs for a second indication: acute myeloid leukemia (AML).

"We were able to statistically significantly increase a remission-free survival for these leukemia patients," said Larry Stambaugh, chairman and CEO of San Diego-based Maxim. "The leukemia patients generally go through chemotherapy and go into remission. Unfortunately, most of these patients relapse in a year, and if you relapse, it's a death sentence."

AML patients and Maxim officials weren't the only ones pleased with Wednesday's news. Investors also welcomed it. The company's stock (NASDAQ:MAXM) rose 70 cents to close at $8.70.

If it all comes to fruition, analysts say Ceplene could become a $1 billion product worldwide as a treatment for multiple cancer indications. Maxim holds all rights to the product.

In the Phase III trial, Ceplene plus interleukin-2 was studied in 320 AML patients at various sites in Europe, North America, Israel, New Zealand and Australia. All patients were in complete remission. The trial sought to discern if the combination therapy could keep patients from relapsing.

The trial met its primary endpoint. Patients treated with the combination therapy experienced a statistically significant (p=0.026) increase in leukemia-free survival, compared with patients in the control arm.

"The control was the standard of care, which today is no treatment," Stambaugh told BioWorld Today.

AML is the most common form of acute leukemia in adults. Patients typically are treated with chemotherapy to achieve disease remission. The longer the patient stays in remission, the better the chance of long-term survival. However, very few stay in remission.

"Generally, it's believed if you get them out to 24 months, there's a high probability to be a long-term survivor," Stambaugh said. "We have the opportunity to have a lot more people live from this disease because of this trial."

Maxim's data cover three years. The patients received 18 months of treatment, and the researchers followed them for another 18 months. Maxim expects to present more detailed data at a scientific meeting later this year, probably the American Society of Hematology meeting in San Diego, Stambaugh said.

Ceplene (histamine dihydrochloride) is the subject of a new drug application for advanced malignant melanoma. Maxim initially filed the NDA in 2000, but the FDA required a second Phase III trial in advanced malignant melanoma with liver metastasis. The company completed enrollment last September. It filed for approval in Europe last fall.

If all goes well, Maxim could gain approval of its first product in Europe later this year and in the U.S. early in 2005. The FDA recently allowed the company to provide the drug, pending approval, as a combination therapy for the most critically ill malignant melanoma patients. Ceplene has orphan drug status in the U.S. in that indication. (See BioWorld Today, April 15, 2004.)

Upon approval of Ceplene in the melanoma indication, Maxim would seek approval in AML under an abbreviated NDA. The drug's ability to show its worth in both a metastatic cancer and a hematological blood-borne cancer indicates it could have strong benefits in other indications as well, Stambaugh said. The company is studying Ceplene in Phase II trials of hepatitis C and advanced renal-cell carcinoma. It also might expand testing of Ceplene into colorectal cancer. Data from the renal-cell trial are expected later this year.

While it waits for regulatory decisions, Maxim is working to find a Ceplene partner in Europe.

"We have kept the rights to Ceplene and we are presently in multiple discussions of partners for ex-U.S. marketing rights," Stambaugh said. "We would hope to identify a partner by the fall, who will help market the drug in oncology indications."

As for the U.S., the company intends to keep its rights, building a sales force of about 40 representatives to market the drug in the melanoma indication.

"These are very targeted markets, and that's something a small biotech can achieve," he said.

Ceplene works by inhibiting oxidative stress, thereby reversing immune suppression and protecting immune cells. It was developed to maintain T cells and natural killer (NK) cells, and improve the efficiency of T- and NK-cell-activating agents, such as IL-2. More than 2,000 patients from 20 countries have participated in clinical trials of Ceplene.