Last week, Novartis announced that the U.S. Food and Drug Administration (FDA) approved the inclusion of Treatment-free Remission (TFR) data in Tasigna (nilotinib).
It is indicated for qualified adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase (CP) after attaining sustained deep molecular response of MR4.5 (BCR-ABL1 International Scale [IS] <= 0.0032%) in its FDA-approved prescribing information.
This is the second regulatory action pertaining to Ph+ CML-CP this month, as earlier in December, the FDA approved a supplemental New Drug Application
(sNDA), expanding the indication for Bosulif (bosutinib) to include patients with newly-diagnosed patients. Almost all patients with the rare cancer have the Philadelphia chromosome. The disease originates in the bone marrow’s blood-generating cells and eventually occupies the blood, resulting in an excess of white blood cells.
BCR-ABL is a protein that promotes abnormal cell growth, and with this approval expansion, Tasigna, a BCR-ABL tyrosine kinase inhibitor (TKI), becomes the only TKI to provide defined, approved criteria to attempt and monitor TFR.
The new indication follows a priority review for an sNDA for Tasigna, which sought out the addition of TFR information and is based on safety and efficacy results from the 96-week analyses of 2 open label trials, ENESTfreedom and ENESTop, which evaluated the potential to maintain major molecular response (MMR) after ending treatment with the therapy.
The studies showed that nearly half of patients remained in treatment-free remission (TFR) for up to 2 years after stopping treatment. The safety data was consistent with the known safety profile for the drug. Rates of musculoskeletal pain-related AEs (all grades) were reduced from 47.9% to 15.1% during the first and second 48 weeks of the TFR phase, respectively, compared to 13.7% during the treatment consolidation phase.
"It has long been our ambition at Novartis to make it possible for some people with CML to discontinue therapy," said Bruno Strigini, CEO, Novartis Oncology in Novartis' official statement
. "We are proud that Tasigna is now the first and only TKI with TFR data in its labeling in the US and several countries around the globe.”
"Patients diagnosed with CML generally face a lifetime of treatment to keep their leukemia from growing or recurring," said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research in a press release
. "Today's approval shows that some patients may be able to stop treatment with Tasigna altogether if they are showing a strong response to therapy. While we welcome this progress in patient care, it's important to note that any discontinuation of treatment still means patients must be regularly monitored for disease recurrence."
The most common side effects in patients who discontinue treatment with Tasigna include musculoskeletal symptoms, like body aches, bone pain and pain in the extremeties. It was noted that severe side effects typically associated with Tasigna administration, including myelosuppression and hemorrhage, occurred less frequently in patients who discontinued treatment.
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