Calistoga Cancer Drug Shows “Encouraging” Preliminary Results in Small Study

10/19/09Follow @xconomy

Seattle-based Calistoga Pharmaceuticals has taken another peek at preliminary results from an ongoing clinical trial of its drug that’s made to block one of the hottest targets in cancer biology, and it continues to like what it’s seeing.

Researchers saw that five of 17 evaluable patients (29 percent) with chronic lymphocytic leukemia had at least partial tumor shrinkage after a single one-month cycle of therapy on Calistoga’s CAL-101 drug candidate by itself, without help from combination therapy, according to data presented over the weekend at a leukemia research meeting in Barcelona. All of the patients had gotten standard treatments before enrolling, and half of them had relapsed before entering the Calistoga trial, researchers said.

The new findings strengthen Calistoga’s body of evidence in a year in which it has started to create some buzz on the national stage. The company raised $30 million in venture capital in May from Frazier Healthcare Ventures, Alta Partners, Three Arch Partners, and Amgen Ventures. A few weeks later, it became clear why Calistoga attracted that much cash. It reported at a pair of cancer meetings that its drug was causing tumor shrinkage in about half of the first 24 evaluated patients in its first clinical trial, even at less than ideal doses, for patients with non-Hodgkin’s lymphoma, acute myeloid leukemia, and chronic lymphocytic leukemia.

The latest data also confirms that Calistoga, along with a number of tough competitors, is pursuing what biologists consider one of the hottest targets in cancer biology. It’s called the PI3 kinase pathway, which controls critical cell processes like proliferation, migration, and cell survival. When these normal functions get flipped into an overactive mode, it’s a hallmark of cancer cells growing out of control as well as an immune system going haywire and attacking healthy tissue.

“We’re seeing robust responses,” in relapsed patients, says Carol Gallagher, Calistoga’s CEO, who I reached by phone while she was attending the meeting in Barcelona. “This is very encouraging data.”

Carol Gallagher

Carol Gallagher

Encouraging as it may be, Calistoga has also learned some important things about side effects. Patients got either a 200 milligram or 350 milligram dose of CAL-101, and saw some signs of elevated liver enzymes in the bloodstream at those doses, which can be a sign of liver damage. The side effects were reversible when patients quit taking the drug, but that effect has gotten Calistoga thinking about whether patients would be better off taking a lower dose in subsequent trials, to strike the best balance between safety and effectiveness, Gallagher says. The company has seen tumor shrinkage with doses as low as 50 and 100 milligrams, she says.

That said, there were other interesting findings from this trial. To put it in context, Gallagher first explained the “partial responses” that are reached when scientists saw at least a 50 percent shrinkage in lymph node tumors, in addition to a 50 percent decline in lymphatic cancer cells circulating through the bloodstream.

That’s important to physicians, but what’s particularly intriguing is the next finding. Calistoga found that 15 of 16 evaluable patients on the drug had at least a 50 percent shrinkage of their lymph nodes, but some of them actually had increases in their lymphatic cell counts in the bloodstream. Those counts went up after initial treatment, but then started dropping over time, Gallagher says. This has prompted Calistoga and its scientific advisors to hypothesize that CAL-101 is essentially able to burrow deep into the bulky tumors of the lymphatic system and the bone marrow, get past the natural defense mechanisms tumors employ in that cellular environment, and flush them out into the circulating bloodstream. That’s something that standard treatments like chemotherapy and rituximab (Rituxan) aren’t very successful at doing, Gallagher says.

Time will tell with more follow-up whether the second, third, and further rounds of CAL-101 treatment will wipe out the circulating cancer cells, Gallagher says. It’s also got the company thinking about designing combination studies that might use CAL-101 to shake loose the bulky tumors in the lymph nodes, and give patients rituximab (Rituxan) when that drug has the best chance to work on cancer cells in the bloodstream, Gallagher says.

“We believe that these patients will ultimately convert from stable disease to partial responders, but we’re not there yet,” Gallagher says.

Cancer often bounces back after a drug shows initial tumor shrinkage ability, so how long will this tumor shrinkage effect really last? There’s not much data on this question, but Calistoga has seen at least one patient have tumor shrinkage continue for at least 224 days. That’s eight cycles of therapy and counting, Gallagher says. Another patient has gone seven cycles without seeing their disease worsen, and another has gone four cycles, she says.

Much more data will be available from Calistoga in December at the American Society of Hematology meeting. The company expects to have data from 80 to 90 patients from various cohorts of patients with chronic lymphocytic leukemia, indolent (slow-growing) non-Hodgkin’s lymphoma, aggressive non-Hodgkin’s lymphoma, acute myeloid leukemia, and multiple myeloma, Gallagher says. Based on that more full set of data, Calistoga plans to start a Phase II/III study that could be used for a new drug application to the FDA, Gallagher says.

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