Celator: Combining chemo drugs for fun and profit

(UPDATED: See below.)Is there a better way to combine drugs in cancer chemotherapy? Celator Pharmaceuticals, a Princeton, N.J., venture drug maker that just raised $10 million, aims to find out.

Like Horizon Therapeutics, which we wrote about here, Celator is convinced that combining two existing drugs in a single formulation at the right proportions can yield better results than current treatments. Although many chemo drugs are already used in combination, the drugs that can be used this way are limited by their side effects. For instance, two chemo drugs that cause severe nausea can’t be used together, because each would have to be given at a less-than-optimal dose in order not to completely debilitate the patient.

In addition, Celator is convinced that various chemo drugs — and here we’re talking about traditional “cytotoxic” chemotherapy that typically kills off all cells that divide quickly, including those that line hair follicles or the digestive tract — tend to work either in concert or at odds depending on the balance in which they’re delivered. So by identifying the drugs that work best together when mixed at an optimum ratio, the company hopes to enhance chemo’s tumor-killing power while minimizing side effects.

Sounds great. Does it work? So far, it’s hard to say. Celator’s lead candidate, CPX-1, is a combination of irinotecan and floxuridine at the cleverly derived molar ratio of, um, one to one. That drug is now in mid-stage human trials. The company’s second candidate, a combination of cytarabine and daunorubicin known as CPX-351, is entering a phase I trial against acute myeloid leukemia.

There are a few cautionary notes. In an earlier “phase I” test of CPX-1 in 26 patients, 15 saw their tumors stabilize for at least two months and two experienced tumor shrinkage (see the PDF “poster” on the study here). Of course, like most early-stage trials, that test wasn’t randomized, controlled or blinded — every patient got the drug — which pretty strongly limits the conclusions you can reasonably draw from it. It certainly doesn’t support the company’s claim in its press release that “over 70 percent of cancer patients in the trial showed a clinical benefit.” For the record, 17/26 is 65 percent, not 70 percent; you can only get to the 70 percent figure by ignoring the data for three patients whose cancer wasn’t “evaluated,” including one who lived less than two weeks after getting the drug. It’s also kind of dicey to claim “clinical benefit” for a drug when you can’t answer the question, “Compared to what?” — which this trial most certainly wasn’t designed to address.

Still, it’s early days for this sort of combination-drug work, and Celator’s investors certainly seem game to tag along. Investors in this follow-on to the company’s $40 million second funding in 2005 included Domain Associates, Quaker BioVentures, TL Ventures, Ventures West Management, GrowthWorks Capital, the Business Development Bank of Canada, and Hearthstone Investment.

The New Jersey Star-Ledger has more here.

UPDATED: Added some additional thoughts on Celator’s claim of “clinical benefit” in its phase I trial.

UPDATE REDUX: Celator’s PR rep lodged a factual objection to the original lead sentence, so I’ve tweaked it.