Can Cell Therapeutics' Rally Last?

Surge of CTIC on PIX301 Trial Data: Sustainable?

Pixantrone is more efficacious than comparators but with safety concerns

Yesterday afternoon (June 1), Cell Therapeutics, Inc. (CTIC) presented updated final results of its pivotal phase III EXTEND (PIX301) trial of Pixantrone in relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) at the 2009 American Society for Clinical Oncology (ASCO) Annual Meeting held in Orlando, Florida.

The PIX 301 EXTEND trial was a phase III single-agent trial of Pixantrone for patients with relapsed or refractory aggressive NHL who received two or more prior therapies and who were sensitive to treatment with anthracyclines. The trial enrolled 140 patients and patients were randomized to receive either Pixantrone (N=70) or another single-agent drug (N=70) currently used for the treatment of this patient population and selected by the physician.

Efficacy data encouraging

The efficacy data were encouraging. Patients treated with Pixantrone achieved 11.4% complete response (CR), 8.6% unconfirmed complete response (CRu) versus 0% CR and 5.7% CRu in the comparator group. The overall response rate (ORR) which includes CR, CRu, and partial response (PR) in the Pixantrone group was 37.1%, versus 14.3% in the comparator group (p=0.003).

Median progression free survival (PFS) for Pixantrone was 4.7 months versus 2.6 months in comparator group (p=0.0074). About 25.7% of all patients who responded to Pixantrone lasted for more than 4 months, versus 8.6% in the comparator group (p=0.012). Median overall survival rate was 8.1 months for Pixantrone versus 6.9 months for comparator -- a positive trend, but not statistically significant (p=0.544).

Concerns about side-effects

Although the efficacy data for Pixantrone were encouraging, we are concerned about its side effects. Pixantrone had much higher grade 3/4 adverse events than comparator for all the grade 3/4 events except for anemia and pyrexia. Notably, Neutropenia was 41.2% for Pixantrone versus 19.4% for comparator. Leukopenia was 23.5% for Pixantrone versus 4.5% for comparator.

Although the grade 3, 4 cardiac disorder was similar among the two treatment groups (1.5% vs. 1.5%), there was a higher incidence of serious cardiac disorders in patients treated with Pixantrone than among patients who received comparator agents (8.8% vs. 4.5%). Events considered cardiac disorders included cardiac arrest, congestive heart failure, myocardial infarction, cyanosis, pericardial effusion, and tachycardia.

The higher-than-expected side effects may limit the utility of Pixantrone in the NHL patients.

As a reminder, CTIC is developing Pixantrone for third-line aggressive non-Hodgkin’s lymphoma (NHL). Pixantrone belongs to a class of cancer medicines known anthracylines. Dosing of anthracyclines is limited, however, due to severe cardiac toxicity.

In April 2009, the company began a rolling submission of a New Drug Application (NDA) to the US FDA for Pixantrone. CTIC expects to complete the submission later this month, and will request priority review which if granted could lead to an approval decision from the FDA in late 2009 or early 2010. Pixantrone is also now available in Europe on a named patient basis.

We are still neutral on CTIC shares at this point.

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