Calistoga Builds More Momentum for Cancer Drug, Eyes Pivotal Trial Next Year

12/8/09Follow @xconomy

Seattle-based Calistoga Pharmaceuticals has gathered more evidence that it may have a real drug for blood cancers, which is shrinking tumors in patients without killing too many other healthy cells in the blood.

The drug, CAL-101, didn’t work for everybody, but it did cause tumors to shrink at least by half for 60 percent of patients with a slow-growing malignancy called indolent non-Hodgkin’s lymphoma, researchers reported today at the American Society of Hematology (ASH) annual meeting in New Orleans. That result was based on 9 out of 15 patients, who were part of a wider study that included 57 patients with a variety of different malignancies.

The new findings are the latest step forward for Calistoga, as it has emerged on the national scene this year. The privately held company raised $30 million in venture capital in May from Frazier Healthcare Ventures, Alta Partners, Three Arch Partners, and Amgen Ventures to pursue drugs that block one of the hot targets of the moment in cancer biology—the PI3 kinase pathway. A few weeks after raising the cash, Calistoga reported interim results at a pair of cancer meetings that showed its drug was causing tumor shrinkage in about half of the first 24 evaluated patients, even at less than ideal doses.

The company has been so encouraged by the early results that it is planning for the next step of clinical trials, to start in the middle of 2010, that could provide the basis for an application to the FDA for clearance to start selling CAL-101 in the U.S.

“Certainly we still have to see the duration of the data, and it’s still early days,” says CEO Carol Gallagher, who was attending the ASH meeting in New Orleans. “But we’re hearing the investigators talk, and it’s rewarding to hear them tell some dramatic stories.”

One of the researchers on the CAL-101 study, Ian Flinn of Sarah Cannon Research Institute in Nashville, TN, said in a Calistoga statement that the results are “very encouraging.”

What did the researchers actually see? There are a lot of numbers to digest, as usual, so I figured a chart might be helpful. Researchers didn’t see any complete responses, in which tumors are totally eradicated, but they did see partial responses, in which tumors shrink by 50 percent or more. Below I’ve separated out different patient groups, and listed how many patients responded to the drug in each group based on what I gathered from Gallagher:

Responders Percentage
Slow-growing “indolent” non-Hodgkin’s lymphoma 9/15 60 percent
Mantle cell lymphoma 6/7 86 percent
Chronic lymphocytic leukemia 4/17 24 percent
Diffuse large B-cell lymphoma 0/5 0 percent
Acute myeloid leukemia 0/9 0 percent

The patients who entered this study were quite sick. About half had relapsed prior to entering the study, and they had received a median of 4.5 treatment cycles. The most common serious side effect of the drug was infection, but researchers saw a “low incidence” of white blood cell and red blood depletion that is common with many chemotherapies, and which makes people feel anemic and vulnerable to infection. That means that the Calistoga drug is likely to be combined with existing treatments, because researchers won’t be so worried about exacerbating that side effect, Gallagher says.

The data being reported at the ASH conference is current as of late October, but more updated data could be available soon. Calistoga has now completed enrollment of all 90 patients in the study, and expects to have one-month evaluations completed on all of them before the end of the year, Gallagher says.

A lot of important questions still need to be answered before Calistoga decides on its next move in larger, more rigorous clinical trials. It wants to see the full data set before it picks an ideal dose for the next round of studies. Many patients got 200 or 350 milligram doses, which caused some patients to have elevated concentrations of liver enzymes in the blood, which can be a sign of liver damage. That effect was reversible when patients quit taking the high doses, and patients have been able to resume taking lower doses later on, Gallagher says.

That’s not too much of a concern, Gallagher says, because this early dose-ranging study of CAL-101 showed that it was able to cause partial tumor shrinkage at doses as low as 50 or 100 milligrams. “We saw activity at all dose levels,” she says.

Some anecdotal reports have been making the rounds during conversations in New Orleans, she says. One was about a female patient who had a lymph node that had enlarged so much that she was having trouble breathing, but within 28 days of taking CAL-101, it shrank by half and enabled the patient to breathe better, Gallagher says. Another patient, a chemistry professor, was getting hospice care, but was able to get back to teaching after taking the drug, she says.

One of the next big steps for Calistoga will be whether it can find a partner to help pay the expensive bills of running pivotal clinical trials. Back in March, the company hired a proven dealmaker in Cliff Stocks, formerly of Icos, as its chief business officer to do just that. Gallagher had nothing specific to say about partnering other than that “we have a lot of interest” at the ASH meeting. She noted that the company is also looking for a partner to help it develop other drugs in its pipeline besides CAL-101, as it branches into treatments for autoimmune diseases and solid tumors.

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