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Novartis Drug Tasigna® Receives FDA Priority Review For Newly Diagnosed Patients With Early-stage Chronic Myeloid Leukemia

I think this is a press release from Novartis. It's in Medical News Today, and I enclose the main text of the article. In summary, the FDA in the USA thinks nilotinib is so good they are prepared to fast track it for approval for newly diagnosed patients.

You've got to ask just where that leaves good old NICE's attitude, haven't you...

"Novartis Drug Tasigna® Receives FDA Priority Review For Newly Diagnosed Patients With Early-stage Chronic Myeloid Leukemia

Article Date: 20 Feb 2010 - 2:00 PST

Novartis announced that Tasigna® (nilotinib) has been granted priority review by the US Food and Drug Administration (FDA) for the treatment of adult patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase.

FDA priority review status is granted to therapies that offer major advances in treatment or provide a treatment where no adequate therapy exists. This status accelerates the standard review time from 10 to six months. Tasigna demonstrated that significantly fewer patients progressed to more advanced stages of the disease than the standard of care Glivec® (imatinib)* at 12 months. Tasigna also showed a statistically significant improvement over Glivec in every other measure of efficacy in the trial, including major molecular response (MMR) and complete cytogenetic response (CCyR) at 12 months[1].

In addition to the US, regulatory submissions have been filed in the EU and Japan. All filings are based on data showing superior efficacy for Tasigna in the first head-to-head comparison of the drug against the standard of care Glivec in newly diagnosed Ph+ CML patients. If approved for the first-line indication, Tasigna will be the first drug for newly diagnosed patients to become available since the approval of Glivec in 2002.

"Recently presented data showed that Tasigna surpassed Glivec in every measure of treatment efficacy designated in the study including prevention of disease progression at 12 months," said David Epstein, CEO of the Novartis Pharmaceuticals Division. "Now this priority review designation brings us one step closer to offering patients who are newly diagnosed with Ph+ CML in the chronic phase a promising new treatment option."

The regulatory submissions are based on data from the ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+ CML Patients) Phase III clinical trial. This randomized, open-label, multicenter trial compared the efficacy and safety of Tasigna versus Glivec in adult patients with newly diagnosed Ph+ CML in chronic phase[1]. It is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients.

In the ENESTnd clinical trial, significantly fewer patients at 12 months progressed to accelerated or blastic phase on Tasigna 300 mg twice daily than on Glivec 400 mg once daily (2 patients vs. 11 patients)[1], demonstrating a significant improvement in disease control. Fewer patients discontinued due to adverse events from the Tasigna 300 mg twice daily arm of the study compared to the Glivec 400 mg once daily arm. No patients in the study had a prolongation of the QT interval >500 milliseconds[1]. In addition, no sudden deaths occurred with either treatment[2].

Tasigna is a potent and selective inhibitor of the Bcr-Abl protein that causes production of cancer cells in Ph+ CML[2],[3]. The first clinical trials of Tasigna began 21 months after its discovery, with the drug receiving its first regulatory approval in the second-line indication in 2007[3].

......."

copy and paste for the whole article:
http://www.medicalnewstoday.com/articles/179834.php

Many thanks to Anjana, Asian CML support group, where I saw the link.

Janet

Well done Janet.

That article must put more pressure on NICE. The only thing that I can pick up after a quick scan through it, is that the Tasigna patients were taking 300mg twice a day. That must raise the cost of Tasigna/patient by quite a lot?

Thanks Janet,
I had posted an article about this under Newswire which you can still find under the news section...see copy below. It is good to hear that the FDA have approved and we can now expect the EMEA (or the Agency as it is now known) which is the European equivalent of the FDA to follow. Still NICE will be a barrier for us in the UK.

Which is why I do not think that an FDA approval will make one bit of difference to NICE. They have already said in both ACD's that they do not accept the data from trials/studies of nilotinib or dasatinib that were presented by either drug company.
We have to fight this incrementally. I do hope both you and Janet can sign the petition. We have 38 so far which is not bad considering I only put it on yesterday..I have even had some signatures from my Facebook page.

Please send the petition link to as many people as you can... especially UK residents.

Thanks again and best wishes,

Nilotinib shows improved response in newly diagnosed CML

www.oncologystat.com/news

Nilotinib Bests Imatinib for Newly Diagnosed Chronic-Phase CML
Elsevier Global Medical News. 2009 Dec 10, S London

NEW ORLEANS (EGMN) - Nilotinib is superior to imatinib for inducing deep remissions in patients with newly diagnosed chronic myeloid leukemia in the chronic phase, according to results of the first head-to-head trial of these two oral agents in this setting.

Compared with imatinib (Gleevec), which is the current standard of care for chronic myeloid leukemia (CML), nilotinib (Tasigna) is a more potent and more selective inhibitor of the BCR-ABL protein that drives the disease, lead author Dr. Giuseppe Saglio said at the annual meeting of the American Society of Hematology.

The major molecular response rate was twice as high in the nilotinib arm of the 846-patient study, he reported. In addition, significantly fewer patients progressed to accelerated phase or blast crisis. "Despite the excellent results that can be achieved with imatinib, progression still occurs in a small proportion of patients and is associated with a poor outcome in terms of overall survival," Dr. Saglio noted.

The randomized, open-label, phase III trial - called ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Patients) - enrolled adults from 35 countries who had received a diagnosis of Philadelphia chromosome-positive (Ph+) CML in chronic phase in the past 6 months. The only prior therapies permitted were hydroxyurea, anagrelide, and up to 2 weeks of imatinib.

The patients were stratified by Sokal risk score and assigned to nilotinib 300 mg twice daily (282 patients), nilotinib 400 mg twice daily (281 patients), or imatinib 400 mg once daily (283 patients).

Overall, the trial population had a median age of 47 years. Importantly, 28% of patients had high-risk Sokal scores, noted Dr. Saglio, who is a hematologist at the University of Turin (Italy).

With a median follow-up of 14 months, the median dose intensity was nearly the same as the planned dose in all three treatment groups. "This means the treatments were well tolerated," he commented. In all, 16% of imatinib patients had dose escalation to 400 mg twice daily, as allowed by the protocol.

The rates of study discontinuation because of adverse events or laboratory abnormalities were 7% with lower-dose nilotinib, 11% with higher-dose nilotinib, and 8% with imatinib.

In intention-to-treat analyses, the 12-month rates of major molecular response (a reduction of the ratio of BCR-ABL:ABL to 0.1% or less on the international scale) were twice as high with nilotinib at the lower dose and the higher dose (44% and 43%, respectively) as with imatinib (22%) (P less than .0001 for both comparisons).

Moreover, patients treated with nilotinib were more likely to have deeper major molecular responses, both in terms of a reduction of the BCR-ABL:ABL ratio to 0.01% or less (24% and 21% vs. 10%) and in terms of a reduction of this ratio to 0.0032% or less - the most sensitive measure of leukemic burden available (13% and 12% vs. 4%).

The 12-month rates of complete cytogenetic response were also better with nilotinib at both the lower dose (80%) and higher dose (78%), compared with imatinib (65%) (P less than .0001 and P = .0005, respectively).

Fully 3.9% of patients assigned to imatinib progressed to accelerated phase or blast crisis, but only 0.7% assigned to lower-dose nilotinib and 0.4% assigned to higher-dose nilotinib did (P = .0095 and P = .0037, respectively). None of the patients who achieved a major molecular response had such progression, whereas three achieving complete cytogenetic response did, Dr. Saglio noted, confirming that "the quality of the response is the best predictor of the risk of undergoing subsequent progression of disease."

Rates of drug-related adverse events of grade 3/4 were generally low in all groups, although grade 3/4 neutropenia occurred in 10%-12% of nilotinib patients and in 20% of imatinib patients. The imatinib group was more likely to experience nausea, muscle spasms, diarrhea, vomiting, and fluid retention of any grade, whereas the nilotinib groups were more likely to experience rash, headache, pruritus, and alopecia of any grade.

Cardiac QTcF prolongation by greater than 30 msec occurred in 26% of nilotinib patients, compared with 18% of their imatinib counterparts, but prolongation by more than 60 msec was rare. None of the patients had a decrease in left ventricular ejection fraction.

"Based on these results, we strongly believe that nilotinib may become the new standard of care in newly diagnosed CML patients," Dr. Saglio concluded.

He disclosed that he is a consultant and a member of the speakers bureau for Novartis and Bristol-Myers Squibb Co.

Imatinib is the standard first-line treatment for Ph+ CML. Nilotinib and dasatinib (Sprycel) are Food and Drug Administration-approved for treatment of patients who become resistant to or intolerant of imatinib therapy. Both drugs are in clinical trials designed to lead to applications for approval as first-line therapies.

Commenting on the nilotinib trial in an interview, Dr. Richard A. Van Etten, director of the Tufts Medical Center Cancer Center in Boston, noted that although responses to imatinib catch up with those to newer tyrosine kinase inhibitors like nilotinib by 18-24 months, patients are at risk for progression in the interim. Aside from cardiotoxicity, the adverse effect profile of nilotinib is better, he noted.

But comparative costs will be an issue, given that imatinib will become generic in 2014, according to Dr. Van Etten. Indeed, he said, some companies claim that they will be able to manufacture the drug for only $5 per treatment day.

"If [nilotinib] gets approved based on [ENESTnd] data," he predicted, "you will find a lot of people using it because the argument will be, why have this vulnerable period and put patients at risk of disease progression when you can give a drug that has a better toxicity profile - costs be damned."

A reasonable alternative strategy, he added, would be to use imatinib with intensive monitoring to catch the rare progressions very early and intervene with salvage therapy.
Submitted by sandy craine on Mon, 2010-01-04 12:39. Sandy