ASH 2009: Novartis looks to position Tasigna as an alternative to Gleevec in CML

June 10, 2010 - PRLog -- ASH 2009: Novartis looks to position Tasigna as an alternative to Gleevec in CML

At this year's American Society of Hematology meeting, researchers presented results from a Phase III study comparing Tasigna and Gleevec in newly diagnosed chronic myeloid leukemia. While Tasigna's efficacy is impressive, it is unlikely that the drug will achieve the same market penetration as Gleevec in newly diagnosed patients due to fierce competition from Sprycel. ( http://www.bharatbook.com/detail.asp?id=68594&rt=Novartis-AG-PharmaVitae-Profile.html )

At the 51st annual meeting of the American Society of Hematology (ASH 2009), Dr Giuseppe Saglio presented the results of a Phase III study comparing Tasigna (nilotinib; Novartis) to Gleevec (imatinib; Novartis) in newly diagnosed chronic myeloid leukemia (CML) patients in chronic phase.

Gleevec is an orally administered Bcr-Abl tyrosine kinase inhibitor (TKI) which in 2001 became the first targeted therapy to reach the market for CML, revolutionizing treatment of the disease and achieving blockbuster sales. Tasigna, meanwhile, is Novartis's second-generation Bcr-Abl TKI, and reached the EU and US markets in 2007 for CML patients resistant or intolerant to Gleevec.

In the study, known as ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients), 846 newly diagnosed chronic-phase CML patients were randomized to receive either Tasigna 300mg twice-daily, Tasigna 400mg twice-daily or Gleevec 400mg once-daily. The study protocol allowed dose escalations in the Gleevec arm, but not in either of the Tasigna arms. The primary endpoint of the study was rate of major molecular response (MMR) at 12 months.

In the Tasigna 300mg and Tasigna 400mg twice-daily arms, the rates of MMR at 12 months were 44% and 43%, respectively. In the Gleevec arm, the rate of MMR at 12 months was 22%. The complete cytogenetic response rate (CCyR) at 12 months was also superior in both Tasigna arms, at 80% for the 300mg arm and 78% for the 400mg arm. In the Gleevec arm, CCyR at 12 months was 65% (with both results also reaching statistical significance). Importantly, Tasigna showed superiority to Gleevec across all risk groups.

According to Dr Saglio, the most important finding from the clinical point of view was the lower rate of progression to accelerated phase or blast crisis (more advanced stages of disease) in the two Tasigna arms. In the Gleevec arm, 4% of patients progressed to accelerated phase or blast crisis at 12 months, whereas less than 1% of patients in each of the Tasigna arms progressed to these stages of disease (a result that reached statistical significance).

Both agents were well tolerated, and close to the full planned dose of therapy was administered in all three arms. The rate of discontinuation due to adverse events or laboratory abnormalities was 7% in the Tasigna 300mg twice-daily arm, 11% in the Tasigna 400mg twice-daily arm, and 9% in the Gleevec arm.

Dr Saglio concluded that Tasigna "may become the new standard-of-care in newly diagnosed CML."

With Gleevec's patent set to expire by 2015 in the US, Novartis will hope that the ENESTnd data enable the company to position Tasigna as the standard of care in newly diagnosed chronic-phase CML before generic versions of Gleevec flood the market. Indeed, the company has announced that it intends to file worldwide regulatory approval applications for this indication by the end of 2009.

The efficacy data reported for Tasigna in this trial are impressive, particularly given the high bar already set by Gleevec. While the data are still preliminary, they show the potential of Tasigna to address one of the key areas of unmet need remaining in CML: preventing progression from chronic phase to accelerated phase or blast crisis. It anticipates that Tasigna will receive approval in 2011 for this indication on the strength of these data, and in the nearer-term it is likely that the drug will receive off-label use in newly diagnosed CML patients. This will significantly boost the market potential of the drug, which is currently restricted to use in a relatively small number of patients.

However, it is less likely that Tasigna will achieve the same high rate of market penetration as Gleevec in newly diagnosed CML patients. Firstly, the drug is likely to face fierce competition from Sprycel (dasatinib; Bristol-Myers Squibb). Sprycel is also in Phase III development for newly diagnosed CML and Phase II data presented at the conference indicate that it also has promising potential in this indication. Importantly for Novartis, however, Tasigna is the first of these two second-generation Bcr-Abl TKIs to show superiority to Gleevec in a Phase III study. This could allow Tasigna to expand its label and gain a foothold in the first-line market ahead of Sprycel.

Another factor that could restrict the uptake of Tasigna in newly diagnosed patients is its high cost compared to Gleevec. Indeed, this cost difference will only widen when generic versions of Gleevec reach the market. Given that the majority of patients achieve durable remissions with first-line Gleevec, it is possible that some physicians - particularly those in more cost-conservative healthcare markets - may continue to treat patients initially with Gleevec and reserve Tasigna (or Sprycel) for patients who lose remission or progress to accelerated phase of blast crisis.

If there is one aspect to the ENESTnd data which Novartis will find disappointing, it is the finding that 400mg Tasigna twice-daily was not superior to 300mg twice-daily. This may also somewhat limit the market potential of Tasigna.

Related research

• Novartis AG: PharmaVitae Profile
http://www.bharatbook.com/detail.asp?id=68594&rt=Novartis...

• Stakeholder Insight: Acute Leukemias - Reaching the limits of cytotoxic chemotherapy
http://www.bharatbook.com/detail.asp?id=114971&rt=Stakeho...

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