Aeterna Zentaris announced this morning that the company will be continuing development of perifosine as a potential treatment for multiple myeloma.

Speculation arose last month that an ongoing Phase 3 trial of perifosine in myeloma might be canceled due to disappointing results from a Phase 3 trial of perifosine in colorectal cancer.

Perifosine ^[1] (KRX-0401) is an orally administered drug that belongs to a new class of anti-cancer drugs known as “Akt-inhibitors.” Akt is a protein believed to play an important role in the development and growth of cancer cells.

Dr. Paul Richardson, from the Dana-Farber Cancer Institute and lead investigator of the Phase 3 myeloma study, explained to the Beacon that there are significant biological differences between multiple myeloma and colorectal cancer and that perifosine targets biological pathways that may be much more important in myeloma.

“Perifosine being disappointing in colorectal cancer doesn’t mean it doesn’t work in myeloma,” said Dr. Richardson. “There have been not only exhaustive preclinical studies [of perifosine in myeloma] but most importantly now three large multicenter Phase 2 trials,” which Dr. Richardson indicated had positive results.

The Canadian biotech company Aeterna Zentaris (NASDAQ: AEZS) licensed the rights to develop and market perifosine in North America to the U.S.-based pharmaceutical company Keryx Biopharmaceuticals (NASDAQ: KERX) in 2002. However, Aeterna Zentaris regained those rights on Friday, after the two companies announced the termination of their license agreement.

Results of the Phase 3 clinical trial in colorectal cancer, which were released April 2, showed that perifosine in combination with chemotherapy did not extend survival of patients with refractory advanced colorectal cancer, compared to chemotherapy alone.

Following the release of the colorectal cancer results, the stocks of both Keryx and Aeterna Zentaris lost two-thirds of their value.

The ongoing Phase 3 trial in multiple myeloma is comparing the combination of perifosine, Velcade ^[2] (bortezomib), and dexamethasone ^[3] (Decadron) to Velcade and dexamethasone alone in relapsed and refractory multiple myeloma patients.  Keryx indicated that recruitment for the trial may become difficult given the lack of positive results in the colorectal cancer study.

Dr. Richardson felt recruitment would not be a problem “as long as patients understand the biological differences that exist between myeloma and colorectal cancer, which are about as big as they can be.”
He explained that Velcade was very potent against colorectal cancer in animal testing but did not work for colorectal cancer in the clinic.

“Does that mean Velcade doesn’t work in myeloma? No. Quite the opposite. When patients hear that kind of example, I think they understand why it doesn’t make sense to exclude perifosine based particularly on the positive results so far,” Dr. Richardson said.

Dr. Richardson indicated that enrollment for the Phase 3 trial would likely be complete within about a year and a half, and the first interim results might be available in two to three years.

For more information, see the Aeterna Zentaris ^[4] press release, previous Beacon ^[5] news articles about perifosine, and the clinical trial description ^[6] for the Phase 3 perifosine trial in multiple myeloma.