Danziten: A Transformative Step in CML Treatment

  • The FDA’s approval of Danziten marks a transformative step in chronic myeloid leukemia treatment, offering a more convenient and patient-friendly option without compromising efficacy.
  • By simplifying the treatment regimen, Danziten reduces the likelihood of missed doses, improving outcomes.
  • The lower dose required with Danziten allows for precision in managing patients with comorbidities or those at risk of long-term adverse effects.
  • For patients, the ability to take their medication without dietary restrictions removes a significant source of stress, promoting overall well-being.

The recent FDA approval of Danziten, a re-engineered formulation of nilotinib, marks a significant milestone in the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). Developed by Azurity Pharmaceuticals, Danziten is the first and only tyrosine kinase inhibitor (TKI) indicated for CML that eliminates the need for mealtime restrictions, offering a more patient-friendly option without compromising efficacy.

“There was a new FDA approval for a drug called nilotinib, which is known as Tasigna previously. However, with Tasigna, you have to avoid taking the drug two hours before or one hour after a meal. And so patients are often limited in how they can take the drug, especially because it’s given twice a day for patients. When they do take to Tasigna around mealtime, it can increase the risk of cardiac arrhythmias,” Dr Catherine E. Lai, Physician Leader at the Leukemia Clinical Research Unit at University of Pennsylvania, tells SurvivorNet Connect.

“With Danziten, the bioavailability is not affected by food. It’s still a twice a day medication. However, it doesn’t matter whether a patient has taken food or not. It’s much more convenient from that standpoint and therefore you don’t have to worry about increasing the concentration of the drug in the system, which causes other side effects,” Dr. Lai explains. “The indication is still the same. Meaning it’s approved for patients who have newly diagnosed chronic phase CML, as well as patients who have CML who have been on a previous line of therapy.”

CML & the Role of Tyrosine Kinase Inhibitors

Chronic myeloid leukemia (CML) is characterized by the presence of the BCR::ABL1 fusion gene, resulting in constitutively active tyrosine kinase activity. This molecular hallmark drives the proliferation of granulocytes, leading to the disease’s characteristic triphasic progression. The introduction of TKIs, such as imatinib and nilotinib, has revolutionized CML management, transforming it into a chronic and manageable condition for most patients.

Adherence to therapy is critical in achieving deep molecular responses and preventing disease progression. However, rigid treatment regimens, including fasting requirements for some TKIs, have posed challenges to adherence.

What Sets Danziten Apart?

Danziten introduces a groundbreaking innovation in CML treatment by removing the fasting restrictions associated with earlier formulations, such as Tasigna.

Key features of Danziten include:

No Mealtime Restrictions

Patients can take Danziten without fasting, liberating them from the two-hour pre-treatment and one-hour post-treatment fasting requirements associated with Tasigna. This is achieved through an improved formulation that ensures consistent pharmacokinetics and bioavailability regardless of food intake.

Equivalent Efficacy at a Lower Dose

Clinical trials have demonstrated that Danziten maintains the same efficacy as Tasigna in both newly diagnosed and previously treated Ph+ CML patients. By enhancing bioavailability, the re-engineered formulation allows for a lower dose, reducing the treatment burden.

Enhanced Safety Profile

The original nilotinib formulation (Tasigna) carried the risk of prolonged QT intervals and potential cardiotoxicity when taken with food. Danziten’s updated formulation minimizes this risk by ensuring steady drug absorption regardless of the fed or fasted state.

Clinical Evidence Supporting Danziten

Data presented at the 2024 Society of Hematology Oncology (SOHO) Annual Conference highlighted Danziten’s pharmacokinetic consistency. Unlike Tasigna, Danziten demonstrates no clinically significant differences in drug exposure, irrespective of mealtime conditions. These findings confirm its reliability as an alternative treatment option.

The ENESTnd trial (NCT00471497) and the A2101 study (NCT00109707), which supported the approvals of both Tasigna and Danziten, provided robust evidence of nilotinib’s efficacy:

-ENESTnd Trial Results: At 12 months, the major molecular response (MMR) rate for nilotinib was 44%, compared to 22% for imatinib (p < 0.0001). At 60 months, 77% of nilotinib-treated patients achieved MMR versus 60% of those treated with imatinib.
-A2101 Study Results: Among patients resistant or intolerant to prior therapy, nilotinib achieved a major cytogenetic response (MCyR) rate of 51%, with complete and partial cytogenetic response rates of 37% and 15%, respectively.

Addressing Adherence in CML Management

Adherence is a cornerstone of successful CML treatment. Nonadherence can lead to suboptimal responses, treatment failure, and disease progression. The introduction of Danziten addresses several barriers to adherence:

1. Simplified Regimen: The elimination of fasting requirements makes the treatment schedule less intrusive, allowing patients greater flexibility in their daily routines.

2. Reduced Treatment Burden: With improved bioavailability, Danziten offers effective disease management at a lower dose, potentially reducing side effects and enhancing tolerability.

3. Improved Patient Support: Azurity Pharmaceuticals has implemented the DanzitenCONNECT program to ensure patients have access to therapy.

This program provides:
-Prior authorization and benefits investigation
-A free initial month of therapy
-Copay reductions (as low as $0 in some cases)
-Assistance through a patient assistance program for those who qualify

These efforts aim to reduce financial and logistical barriers, further supporting adherence.