a notoriously tough disease to treat, and tumors that get shrunk by some drugs often show an amazing resilience to bounce back and kill people just as if they received no drug at all. Calistoga is still collecting data on the “durability” of effect from its drug, and doesn’t have enough information yet to say how long its drug can keep tumors in check, much less whether it can help people live longer. So far, the company can say that 12 patients have shown they respond to the drug for more than six months.
Importantly, Calistoga has learned from this small study where its drug doesn’t seem to help. The company enrolled 31 patients with multiple myeloma, acute myeloid leukemia, and diffuse large B-cell lymphoma, and saw zero instances of 50 percent tumor shrinkage or greater.
All of this has provided a rich set of data for Calistoga to craft a strategy for the next round of clinical trials, Gallagher says. This trial will probably grow to a total of 150 patients, as Calistoga experiments with getting the right dose, and enrolling a few more people with slow-growing non-Hodgkin’s lymphoma.
Once that database is complete, Calistoga plans to sit down with the FDA to talk about the best design for a pivotal clinical trial that could pave the way for the company to start selling its drug in the U.S. Such a study will be bigger, and will likely enroll patients with indolent (slow-growing) lymphoma, and chronic lymphocytic leukemia, Gallagher says. It will likely not be required to randomly assign patients to directly compare the new drug against a standard treatment, and it won’t need to show the new drug helps people live longer, Gallagher says. Calistoga’s main benchmark will probably be GlaxoSmithKline’s ofatumumab (Arzerra), which has shown in relapsed patients that it can shrink tumors in about 42 percent of patients, with a median duration of response of 6.5 months, according to the drug’s prescribing information.
When used as a single agent, the Calistoga drug has shown in this small study that it can cause tumor shrinkage rates in the 50 to 60 percent ballpark, which gives the company confidence that it can provide an advance over the existing standard of care, Gallagher says. But one trial obviously isn’t enough to prove that. If the company can get the FDA to agree on its pivotal trial plan, it should start that study in the second half of 2010, Gallagher says. Before the end of June 2011, it hopes to start a more rigorous study that randomly assigns patients to the Calistoga drug or another treatment to strengthen the body of evidence it will need to persuade physicians to prescribe the product. Calistoga is also looking to raise the bar on tumor shrinkage rates by combining its treatment with a couple of proven therapies in the world of blood cancers—Roche and Biogen Idec’s rituximab (Rituxan) and Cephalon’s bendamustine (Treanda). There are also possibilities of combining the Calistoga drug with other drugs designed to block other enzymes like mTOR and Akt, Gallagher says. She’s been running through a full slate of meetings at this year’s ASCO conference with doctors and prospective pharmaceutical industry partners, to talk about all the options on the table.
“It will be interesting to see all the data here at ASCO,” Gallagher said on Friday, on the eve of the meeting. “I think this is one of the most active single-agent studies being presented. We’ve seen quite a robust response rate.
Of course, Calistoga’s not the only company touting a drug at ASCO with an encouraging response rate in a preliminary study. It will mean a lot more if Calistoga, and its competitors, can advance through the final stage of development and get their new drugs on the market. “The good news for patients is we are starting to get targeted therapies that are effective and less toxic than traditional chemotherapies,” Gallagher says.
