Biotech Values

[DewDiligence]

Tasigna Bests Gleevec at 18 Months in 1st-line CML

[The 12-month data from this study, which were reported at ASH in December (#msg-44330980), were the basis for the NDA submission in Feb 2010 to expand the Tasigna label to the first-line setting (#msg-46819994). The presentation at ASCO described here consists of 18-month data from the same study. The primary endpoint was major molecular response (MMR), defined as a >=3-log reduction in Bcr-Abl relative to an industry-standard value for untreated patients. Tasigna is battling BMY’s Sprycel for the honor of inheriting the Gleevec mantle in CML; a head-to-head study will be presented this weekend.]

http://finance.yahoo.com/news/New-Data-at-ASCO-Show-prnews-1782193640.html?x=0&.v=1

›New Data at ASCO Show Novartis Drug Tasigna® Surpasses Gleevec® for Newly Diagnosed CML Patients

• 18-month median follow-up from the first head-to-head comparison of these two oral therapies to be presented Monday, June 7 at ASCO

• Three times more patients achieved undetectable disease at the molecular level with Tasigna than with Gleevec

• In this study, Tasigna produced significantly deeper molecular responses and reduced progression to advanced disease, resulting in fewer deaths due to CML

• Tasigna registration data further confirmed by this new data; filing received FDA priority review and also submitted in EU, Switzerland and Japan

Friday June 4, 2010, 1:23 am EDT

EAST HANOVER, N.J., June 4 /PRNewswire/ -- Novartis announced today 18-month results (median follow-up) showing that Tasigna® (nilotinib) capsules significantly surpass the efficacy of Gleevec® (imatinib mesylate) tablets* in adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase.

This 18-month median follow-up is from the first head-to-head comparison of these two oral therapies as initial treatment for this life-threatening blood cancer and will be presented on June 7 at the 46th American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

Tasigna produced significantly deeper levels of molecular response than Gleevec in front-line Ph+ CML and reduced progression to accelerated phase and blast crisis, resulting in fewer deaths due to CML. Notably, three times more patients achieved undetectable disease at the molecular level with Tasigna than with Gleevec. Further, Tasigna surpassed Gleevec in other key measures of treatment efficacy.

"Tasigna demonstrates that by more selectively inhibiting BCR-ABL, the key driver of Ph+ CML, we can reduce progression to advanced disease even further than with the current gold standard Gleevec," said Richard Larson, MD, ENESTnd study investigator and Director of the Hematologic Malignancies Program at the University of Chicago. "The efficacy and safety findings achieved by Tasigna in this study provide patients and physicians with an important potential new treatment option."

In February 2010, the US Food & Drug Administration (FDA) granted Tasigna priority review status for newly diagnosed Ph+ CML patients. Regulatory submissions have been filed in the European Union (EU), Switzerland and Japan. The new ENESTnd data to be presented at ASCO will further confirm the findings in those filings, all of which were based on 13.8-month median follow-up data from the study.

Study details

The clinical trial, Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), is a Phase III randomized, open-label, multicenter trial comparing the efficacy and safety of Tasigna versus Gleevec in adult patients with newly diagnosed Ph+ CML in chronic phase. It is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients.

ENESTnd is being conducted at 217 global sites with 846 patients enrolled. Patients were randomized to receive Tasigna 300 mg twice daily (n = 282), Tasigna 400 mg twice daily (n = 281) or Gleevec 400 mg once daily (n = 283). The primary endpoint was major molecular response (MMR) at 12 months; a secondary endpoint was complete cytogenetic response (CCyR) by 12 months. Planned follow-up is for five years. Patients on the Gleevec treatment arm who had suboptimal response or treatment failure were allowed to escalate dose and/or switch to Tasigna via a protocol extension. The data to be presented at ASCO is the 18-month median follow-up.

MMR was defined in the study as reduction in the level of the abnormal BCR-ABL gene to less than or equal to 0.1% of the pretreatment level based on an internationally agreed standard. Notably, three times more patients in the ENESTnd study achieved undetectable disease at the molecular level (BCR-ABL levels at 4.5-log reduction) with Tasigna than with Gleevec, at the 18-month median follow-up. CCyR indicates that no CML cells containing the diagnostic Philadelphia chromosome can be seen in a sample of bone marrow taken from the patient.

Results showed that fewer patients progressed to accelerated phase or blast crisis on Tasigna at 300 mg twice daily (n = 2) and 400 mg twice daily (n = 1) versus Gleevec at 400 mg once daily (n = 12) with 18 months of median follow-up, demonstrating an improvement in disease control. The data also showed fewer deaths due to CML on Tasigna at 300 mg twice daily (n = 2) and 400 mg twice daily (n = 1) versus Gleevec at 400 mg once daily (n = 8). Rate of MMR and CCyR remain superior for Tasigna versus Gleevec at the 18-month median follow-up.

All patients had a minimum of 16 months of treatment or discontinued early; the median follow-up was 18 months. Overall, 80%, 81% and 75% of patients remained in the study on Tasigna 300 mg twice daily, Tasigna 400 mg twice daily and Gleevec 400 mg once daily, respectively.

Both Tasigna and Gleevec were well tolerated overall. Rates of discontinuation due to adverse events or laboratory abnormalities were 7% for Tasigna 300 mg twice daily, 11% for Tasigna 400 mg twice daily, and 9% for Gleevec 400 mg once daily. Fewer patients taking Tasigna discontinued due to adverse events compared to Gleevec. No patients in the study had prolongation of QT interval >500 milliseconds. No sudden deaths occurred in any of the treatment arms.

About Ph+ CML

CML is a disease in which the body produces cancerous white blood cells. Almost all patients with CML have an abnormality known as the Philadelphia chromosome, which produces a protein called BCR-ABL. BCR-ABL causes malignant white blood cells to proliferate. Worldwide, CML is responsible for approximately 10% to 15% of all adult cases of leukemia, with an incidence of one to two cases per 100,000 people per year.

About Tasigna

Tasigna has been approved in more than 80 countries for the treatment of chronic phase (CP) and accelerated phase Ph+ CML in adult patients resistant or intolerant to at least one prior therapy, including Gleevec. The effectiveness of Tasigna for this indication is based on confirmed hematologic and unconfirmed cytogenetic response rates. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.‹