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FDA Approves Nilotinib Tablets Without Mealtime Restrictions for CML

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https://www.onclive.com/view/fda-approves-nilotinib-tablets-without-meal...

Key Takeaways

Nilotinib (Danziten) is approved for Ph-positive CML without mealtime restrictions, offering convenience over Tasigna, which requires fasting.

Danziten maintains equivalent efficacy to Tasigna, with improved bioavailability allowing for a lower dose and no fasting requirements.

Clinical trials showed significant molecular and cytogenetic response rates for nilotinib, supporting its approval for newly diagnosed and pretreated CML patients.

Danziten's consistent pharmacokinetics ensure no significant differences in nilotinib exposure, regardless of fasting state or meal type.
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The FDA has approved nilotinib (Danziten) tablets with no mealtime restrictions for the treatment of adult patients with newly diagnosed Philadelphia chromosome (Ph)–positive chronic myeloid leukemia (CML) in chronic phase (CP-CML); and adult patients with CP- and acute phase (AP)–CML resistant or intolerant to prior therapy that included imatinib (Gleevec).1

Nilotinib (Tasigna) was initially approved by the FDA in 2007 for the treatment of adult patients with Ph-positive CP- and AP-CML who were resistant or intolerant to prior therapy that included imatinib.2 In 2010, the agent was approved in another indication for the treatment of adult patients with newly diagnosed Ph-positive CP-CML.

"Danziten offers a new nilotinib treatment option with the equivalent efficacy to Tasigna, but without the fasting requirements of Tasigna," Richard Blackburn, chief executive officer of Azurity Pharmaceuticals, stated in a news release.1 "Unlike Tasigna, the boxed warning on the Danziten label has no requirement for patients to take their medication in a fasted state, liberating CML patients from mealtime restrictions."

The prescribing information for Tasigna specifies that patients should avoid food for 2 hours prior to treatment and 1 hour after treatment.2 Azurity Pharmaceuticals—the developer of Danziten—noted that the bioavailability of Tasigna varies, and this bioavailability increases when the agent is taken with food.1 When taken with food, Tasigna could lead to a significantly prolonged QT interval.

As a re-engineered formulation of nilotinib, Danziten features improved bioavailability that allows for a lower dose and its consumption without mealtime restrictions without compromising the efficacy displayed by Tasigna. Danziten has demonstrated consistent pharmacokinetics without clinically significant differences in nilotinib exposure, irrespective of fasting state or meal type.

The phase 3 ENESTnd (NCT00471497) and the phase 1/2 Study A2101 (NCT00109707) supported the respective approvals of Tasigna in newly diagnosed Ph-positive CP-CML and pretreated CP- or AP-CML; both trials are listed in the clinical trial evidence in the prescribing information for Danziten.3

Data from ENESTnd showed that patients treated with nilotinib (n = 282) experienced a 12-month major molecular response (MRR) rate of 44% (95% CI, 38.4%-50.3%) compared with 22% (95% CI, 17.6%-27.6%) for those given imatinib (n = 283; P < .0001). The 24-month MMR rates were 62% (95% CI, 55.8%-67.4%) and 38% (95% CI, 31.8%-43.4%), respectively. At 60 months, 77% of patients in the nilotinib arm achieved a MRR vs 60% of patients in the imatinib arm.

Data from the single-arm Study A2101 demonstrated that nilotinib elicited an unconfirmed major cytogenetic response (MCyR) rate of 51% (95% CI, 46%-57%) in patients with resistant or intolerant Ph-positive CP- or AP-CML (n = 321). The complete and partial CyR rates were 37% (95% CI, 32%-42%) and 15% (95% CI, 11%-19%), respectively. The confirmed hematologic response rate was 39% (95% CI, 31%-48%).

References

Azurity Pharmaceuticals, Inc. announces FDA approval of Danziten (nilotinib) tablets, the first and only nilotinib with no mealtime restrictions. News release. Azurity Pharmaceuticals. November 14, 2024. Accessed November 14, 2024. https://azurity.com/azurity-pharmaceuticals-inc-announces-fda-approval-o...
Tasigna. Novartis. Updated June 2010. Accessed November 14, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022068s004s005...
Danziten. Azurity Pharmaceuticals. November 2024. Accessed November 14, 2024. https://danziten.com/wp-content/uploads/2024/11/Danziten-Prescribing-Inf...

This is amazing, having to fast has become 2nd nature for me now but not having to think about this in the future is great. Also the reduced dose is also appealing. I am 7 years on Nilotinib and potentially looking to reduce dose over the coming months, this could be a decent option to when/if it arrives in the UK. I wonder if this version of Nilotinib is potentially better on the body than Tasigna, I've been told Tasigna over the long term is very toxic for the cardiovascular system and the heart plus diabetes and many other potential mormidities.

Al

I agree this is a big deal. I too have become accustomed to the fasting regimen and I actually think it helps to regulate my weight. But anything to make life easier is good in my book.

It's interesting that original formula nilotinib (Tasigna) shouldn't be taken with food because it increases bioavailability,

"Food-Effects
The bioavailability of nilotinib is increased by food. Tasigna must not be taken in conjunction with food (see sections DOSAGE REGIMEN AND ADMINISTRATION and INTERACTIONS) and should be taken 2 hours after a meal. No food should be consumed for at least one hour after the dose is taken.
Grapefruit juice and other foods that are known to inhibit CYP3A4 should be avoided at any time."

and that asciminib (Scemblix) decreases bioavailability with food,

"Effect of Food
The AUC and Cmax of asciminib decreased by 62% and 68%, respectively, with a high-fat meal (1000 calories, 50% fat) and by 30% and 35%, respectively, with a low-fat meal (400 calories, 25% fat) compared to the fasted state following administration of SCEMBLIX.".

That is interesting - I had always known that nilotinib and food equaled overdose, and had assumed the same about asciminib. But but he looks of it, food and asciminib = lower than desired dose.

I’ve been learning quite a bit about food / drug / drug interactions this week. I had always thought imatinib was the only TKI that was OK with PPIs to reduce stomach acid, but it seems asciminib is fine with that too. And there is also Daruph, which is a new formulation of dasatinib which is fine with PPIs too.

We are fortunate for continued drug development for our condition.

David.