Telik Announces Positive Phase 2 Results of a Multicenter Study of Ezatiostat Hydrochloride Tablets in Patients with Myelodysplastic Syndrome
PALO ALTO, Calif., June 8 /PRNewswire-FirstCall/ -- Telik, Inc. (Nasdaq: TELK) today announced positive results from a Phase 2 multicenter trial of ezatiostat hydrochloride (TELINTRA, TLK199) tablets in patients with an International Prognostic System Score (IPSS) low to intermediate-1 risk myelodysplastic syndrome (MDS).
The primary objective of the study was to determine the Hematologic Improvement (HI) rate according to the International Working Group criteria (IWG, 2006). Since MDS comprises a spectrum of heterogeneous disorders with multiple molecularly distinct diseases and overlapping clinical features, an additional goal of this study was to identify those patients whose disease characteristics may allow us to prospectively target patients most likely to respond to Telintra treatment.
Eighty-seven patients were randomized and treated at 23 investigational sites. After initial dose ranging in 14 patients, two dose levels were selected for further study. Subsequently, 37 patients were treated at 3 gm daily for two weeks followed by a one week rest period, and 36 patients were treated at 2 gm daily for three weeks followed by a one week rest period. The data on these 73 patients was pooled for this preliminary analysis.
The median age was 72 years, with a patient population distribution of IPSS low risk (23 patients, 32%) and intermediate-1 risk (50 patients, 68%). Patients had received a median of three prior MDS therapies including 34 patients (47%) with prior Revlimid® (lenalidomide), and 28 patients (38%) with prior DNA methyltransferase inhibitors (DMTI) [azacitadine, decitabine].
At the time of preliminary analysis, 8 patients remain on treatment for continuing clinical benefit. The overall Hematologic Improvement - Erythroid (HI-E) rate was 22%, 13 of 60 evaluable patients, (95% CI, 12.1–34.2). The median duration of HI-E response was 46 weeks (range 2–51). The median hemoglobin level increased by 2.0 gm/dL in responders. Eleven of 38 red blood cell (RBC) transfusion-dependent patients (29%) had clinically significant RBC transfusion reductions (reduction of 4U/8 weeks, IWG 2006) with 4 patients (11%) achieving RBC transfusion independence and 3 patients continuing on treatment. In addition, one patient continues in remission for more than 12 months following discontinuation of therapy (Quddus, et. al., J. Hem. and Onc. Apr. 2010, 3:15).
Telintra continues to demonstrate multilineage hematologic improvement. There was a 15% Hematologic Improvement - Neutrophil (HI-N) rate observed in 3 of 20 patients, (95% CI, 3.2–37.9), and the bilineage HI rate (HI-E and HI-N) was 11%, 2 of 19 patients, (95% CI, 1.3–33.1).
There were three cytogenetic complete responses, one in a patient with 45X,-Y, 46, XY  abnormal cytogenetics that converted to normal after four cycles of therapy. Of the four patients enrolled in the study with del 5q minus, two had a complete cytogenetic response, including one who had failed prior Revlimid therapy.
A planned logistic regression analysis was used to evaluate all known prognostic characteristics in order to define those patients who have an increased likelihood of HI-E response to Telintra. Prior DMTI treatment predicts a five-fold decrease in the odds for a HI-E response to Telintra (p=0.023). Prior Revlimid treatment was observed to enhance HI-E response to Telintra.
•There was a 40% HI-E rate (6 of 15 patients, 95% CI,
16.3%–67.7%), in patients who had prior Revlimid treatment,
but no prior DMTI treatment. Within this patient group, five of 11
patients (45%) achieved significant RBC transfusion reduction with
three patients (27%) achieved transfusion independence.
•There was a 26% HI-E rate (6 of 23 patients, 95% CI, 10.2%–48.4%), in patients who had no prior Revlimid treatment and no prior DMTI treatment. Within this group, five of 11 patients (45%) achieved significant RBC transfusion reduction.
•There was a 0% HI-E rate (0 of 17 patients, 95% CI, 0%-19.5%), in patients who had no prior Revlimid treatment but who had received prior DMTI treatment.
More than 403 cycles of Telintra therapy have been administered. The safety data is based on all patients treated. The most common nonhematologic adverse events (AEs) were Grade 1 and 2 gastrointestinal (GI) respectively, nausea (45%, 16%), diarrhea (25%, 7%) and vomiting (30%, 12%). Grade 3 events were uncommon: nausea (1%), diarrhea (3%) and vomiting (2%). Prior DMTI treatment was associated with an increased incidence of GI AEs.
Telintra treatment may result in clinically significant hematologic improvement in patients with MDS and may offer an alternative to RBC transfusions. The HI rates were consistent with the Phase one results with Telintra, the first GSTP1-1 enzyme inhibitor, tested in MDS. The duration of response was enhanced using the extended dose schedules.
An observation from this trial is that prior Revlimid or DMTI treatment may influence HI-E response to subsequent Telintra treatment. This provides a guide for patient selection for future clinical trials, as well as assists ongoing pharmacogenomic studies to characterize the genomic profile of responders. Telik plans to report final results from this trial at a scientific meeting. A phase 2 study of Telintra in combination with Revlimid in MDS is in progress.
Background on MDS and TELINTRA
The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis (blood cell production) involving one or more cell lineages (red blood cells, white blood cells or platelets) and a variable risk of transformation to acute myeloid leukemia (AML). MDS becomes more common with age. It is estimated that MDS affects approximately 300,000 people worldwide. According to the American Cancer Society, 10,000–20,000 new cases of MDS are diagnosed each year in the United States, with survival rates ranging from six months to six years. MDS patients often require blood transfusions to manage their disease.
There remains a critical need for effective, well tolerated therapies for MDS. Telintra has a novel mechanism of action that inhibits an enzyme called glutathione S-transferase P1-1 which may activate JNK kinase, a key regulator of cellular growth and differentiation of blood precursor cells. Telintra has been shown to stimulate normal multilineage differentiation of blood stem cell precursors and induce cancer cell death, or apoptosis, in human leukemia cell lines. Additional information on Telintra is available at www.telik.com
Telik, Inc. of Palo Alto, CA, is a clinical stage drug development company focused on discovering and developing small molecule drugs to treat cancer. The company's most advanced drug candidates in clinical development are Telintra, a modified glutathione analog for the treatment of MDS and Severe Chronic Neutropenia (SCN), and Telcyta® a cancer activated prodrug for the treatment of advanced non-small cell lung cancer and ovarian cancer. Telik's product candidates were discovered using its proprietary drug discovery technology, TRAP®, which enables the rapid and efficient discovery of small molecule drug candidates.
This press release contains "forward looking" statements regarding the future development of Telintra, the effectiveness of Telintra in treating MDS alone and in combination or following treatment with other drugs, whether Telintra treatment results in hematologic improvement in patients with MDS or offers an alternative to RBC blood transfusions, other potential indications for Telintra, including the treatment of SCN, and the use of Telcyta for the treatment of advanced non-small cell lung cancer and ovarian cancer. These forward looking statements are based upon Telik's current expectations. There are important factors that could cause actual results to differ materially from those indicated by these forward-looking statements including among others, if any clinical trial of Telintra is delayed or unsuccessful, Telik's business would suffer; Telik's business would be adversely affected if it is unable to secure partners or raise funding for the continued development of its product candidates; if Telik's competitors develop and market products that are more effective than its product candidates or any product that Telik may develop, or obtain marketing approval before Telik does, Telik's commercial opportunity will be reduced or eliminated; and if Telik does not obtain regulatory approval to market products in the United States and foreign countries, Telik will not be permitted to commercialize it product candidates. Detailed information regarding factors that may cause actual results to differ materially from the results expressed or implied by statements in this press release may be found in Telik's periodic filings with the Securities and Exchange Commission, including the factors described in the section entitled "Risk Factors" in its quarterly report on Form 10-Q for the quarter ended March 31, 2010. Telik does not undertake any obligation to update forward looking statements contained in this press release.
Telik, the Telik logo, TELINTRA, TELCYTA and TRAP are trademarks or registered trademarks of Telik, Inc.
SOURCE Telik, Inc.
Posted: June 2010