The numbers may be too small to allow any firm conclusions to be drawn, but Clavis Pharma ASA reported positive Phase II data for a combination of elacytarabine and idarubicin in patients with early stage acute myeloid leukemia (AML) who had either relapsed on or proved refractory to a first-line therapy that included cytarabine.

The drug, a modified form of cytarabine, elicited a complete response in 13 of 46 evaluable patients (28 percent) and an overall response rate of 43.5 percent of the per-protocol population. The trial originally recruited 51 patients.

"With any response in the 20s, we wouldn't be very enthusiastic; anything above 30 percent we would be happy with; 43 percent is a good signal," Olav Hellebø, CEO of Oslo, Norway-based Clavis told BioWorld Today.

The data, presented Sunday during the American Society of Hematology meeting in Atlanta, helped to keep the company's jittery investors onside, in advance of crucial data from a Phase III monotherapy trial in 380 patients with advanced AML. The readout is expected late in the first quarter of 2013.

Shares in Clavis (OSLO:CLAVIS) peaked Monday at NOK8.89 (US$1 .56), up 18 percent on Friday's close of NOK7.56. It held onto most of those gains, ending the day at NOK8.70, up 15 percent.

The stock was starting from a low base, however. Investors in the company were badly burned a month ago, when Clavis and its partner, Clovis Oncology Inc., of Boulder, Colo., reported that a drug based on the same modification technology, CO-101 (CP-4126), failed to demonstrate any impact on survival in a pivotal Phase II trial in metastatic pancreatic cancer. (See BioWorld Today, Nov. 13, 2012.)

CO-101 was conceived as a method of bypassing low levels of expression of a perceived resistance mechanism to gemcitabine in pancreatic cancer. Gemcitabine normally enters the cells via a transporter protein called human equilibrative nucleoside transporter-1 (hENT1), but the addition of a hydrophobic elaidic acid lipid tail enables it to enter cells via passive diffusion instead.

In the trial, however, there was no correlation between hENT1 expression and gemcitabine response. "The problem wasn't there, so there was no problem to fix," Hellebø explained.

In AML, hENT1 expression is only part of the story. Although elacytarabine is, unlike cytarabine, independent of hENT1 expression, the addition of the elaidic acid moiety also improves the drug's resistance to enzymatic breakdown, ensuring that higher levels of active drug remain in circulation.

The drug also is retained longer within the cell, resulting in a stronger inhibition of DNA synthesis.

Elacytarabine already has completed a Phase II monotherapy trial in 61 patients with advanced AML. The drug attained a six-month survival rate of 43 percent, while median overall survival was 5.3 months (vs. 1.5 months for matched historical controls) and 10 patients were referred for stem cell transplantation after treatment.

"Bone marrow transplant is the only hope for a cure. That's always the goal," Hellebø said. In the present study, 13 of the 46 evaluated patients were referred for transplant.

For now, however, it's very much a waiting game for Clavis and its investors. The Phase III Clavela data will determine whether the program has a future. The day of reckoning is not far off.