Biotech Values

[DewDiligence]

NVS’ Tasigna Superior to Gleevec in 1st-Line CML

[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. (MMR is a weaker endpoint than Complete Molecular Response (CMR), which is generally defined as either a 4.5-log drop relative to the standardized baseline value or undetectable Bcr-Abl by PCR analysis.) Tasigna is battling BMY’s Sprycel for the honor of inheriting the Gleevec mantle in CML, but these newer drugs still lack approval in the first-line setting.]

http://finance.yahoo.com/news/Novartis-drug-TasignaR-meets-prnews-155214139.html?x=0&.v=1

›- Tasigna meets primary endpoint in pivotal trial against Gleevec as first-line treatment in chronic myeloid leukemia patients

- Tasigna produced faster and deeper responses compared to Gleevec as first-line treatment in Philadelphia chromosome-positive chronic myeloid leukemia

- First registration study using molecular response as key indicator of patient outcomes; Bcr-Abl biomarker test measures very low levels of residual disease

- Tasigna is a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells

- Complete results to be submitted for presentation at the American Society of Hematology (ASH) meeting in December

1:15 am EDT, Tuesday October 20, 2009

EAST HANOVER, N.J., Oct. 20 /PRNewswire/ -- Novartis announced today that Tasigna (nilotinib) 200 mg capsules met its primary endpoint in the first head-to-head comparison with the company's groundbreaking drug Gleevec (imatinib mesylate) tablets. Tasigna produced faster and deeper responses than Gleevec when given as first-line therapy for adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase. Tasigna was well tolerated in the study .

The Phase III clinical trial, Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients (ENESTnd), is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients. Designed to detect a difference in major molecular response (MMR) between Tasigna and Gleevec after 12 months of treatment, it is also the first registration study in which molecular traces of a key biomarker specific to Ph+ CML have been used as a primary endpoint for regulatory review. The comparison study also met its secondary endpoint, a difference in complete cytogenetic response (CCyR) in favor of Tasigna .

"We developed Tasigna to be a potent and selective inhibitor of Bcr-Abl, with the goal of eliminating the underlying cause of Ph+ CML. We now know that Tasigna reduces the level of Bcr-Abl faster and to a lower level than Gleevec, with profound implications for improving patients' outcomes," said David Epstein, President and CEO of Novartis Oncology and Novartis Molecular Diagnostics. "Molecular monitoring enables us to evaluate whether patients have achieved this deep level of CML residual disease, reducing the fundamental biomarker of leukemia to nearly undetectable levels."

The blood test used to determine molecular response can detect a single cell containing traces of Bcr-Abl in up to one million normal blood cells. In addition to being simpler and less invasive for patients, the test has a much greater sensitivity than standard cytogenetic tests , which require a sample of bone marrow to be drawn for visual detection of cells containing the Ph chromosome . Molecular monitoring measures the deepest level of CML residual disease .

Details of the ENESTnd findings will be submitted as a late-breaking abstract to the 51st annual meeting of the American Society of Hematology (ASH), to take place in December in New Orleans, Louisiana, USA.

Ongoing studies of Tasigna as first-line therapy for patients with newly diagnosed Ph+ CML include the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) study, an open-label, single-stage, multicenter Phase II clinical trial; and NCT00129740, an open-label, single-center Phase II clinical trial undertaken at M.D. Anderson Cancer Center in Houston, Texas, USA. New data from the GIMEMA study presented earlier this year at the European Hematology Association (EHA) congress show that at 12 months, 85% of patients taking Tasigna achieved MMR. These data indicate a more rapid reduction in disease burden compared to that seen in previous studies with Gleevec .

Study details

ENESTnd is a Phase III randomized, open-label, multicenter study comparing the efficacy and safety of Tasigna versus Gleevec in adult patients with newly diagnosed Ph+ CML in chronic phase .

ENESTnd is being conducted at 220 global sites, with 846 patients enrolled. Patients were randomized to receive Tasigna 400 mg twice daily (n = 281), Tasigna 300 mg twice daily (n = 282) or Gleevec 400 mg daily (n = 283). The primary endpoint was MMR at 12 months; the secondary endpoint was complete cytogenetic response (CCyR) by 12 months. Planned follow-up is for five years .

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 73 countries for the treatment of chronic phase 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.‹