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Panobinostat, an orally administered histone deacetylase inhibitor, has been approved as a treatment for multiple myeloma, the first treatment in this class to be approved for this type of malignancy, the Food and Drug Administration announced on Feb. 23.
The approval is for use in combination with bortezomib and dexamethasone for treating patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. This is an accelerated approval, based on a surrogate endpoint considered “reasonably likely to predict clinical benefit to patients,” and the manufacturer is required by the FDA to conduct a confirmatory trial for full approval. The indications section of the prescribing information includes the following statement: “This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”
Originally, the manufacturer, Novartis Pharmaceuticals, filed for approval of panobinostat, combined with bortezomib (Velcade), a proteasome inhibitor, and dexamethasone, as a treatment for patients with multiple myeloma who had received at least one prior therapy, based on the results of the PANORAMA-1 (Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma) study. At a meeting in November 2014, the majority of the FDA’s Oncologic Drugs Advisory Committee voted that the benefits of treatment did not outweigh the risks for this indication, although panelists said that there was evidence that panobinostat had biologic activity against multiple myeloma and had an effect on PFS.
After the meeting, Novartis submitted more data that supported approval in the patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent, according to the FDA statement. Among 193 patients in the study who had received at least two other treatments that included bortezomib and an immunomodulatory agent, the median PFS was about 10.6 months among those who were treated with the three agents, vs. 5.8 months among those on bortezomib and dexamethasone only. The response rate was 59% among panobinostat-treated patients, vs. 41% of those on bortezomib and dexamethasone only.
This approval is “particularly important because it has been shown to slow the progression of multiple myeloma,” Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement. He referred to the novel mechanism of action of panobinostat as “making it a potentially attractive candidate agent for the treatment of multiple myeloma.”
The prescribing information includes a boxed warning that says severe diarrhea affected 25% of treated patients, and that treated patients have developed severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes. The drug is approved with a Risk Evaluation and Mitigation Strategy (REMS) addressing these risks.
The most common adverse events associated with panobinostat included diarrhea, fatigue, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting, and weakness; the most common laboratory abnormalities were hypophosphatemia, hypokalemia, hyponatremia, an increased creatinine level, thrombocytopenia, leukopenia, and anemia, according to the FDA statement.
Citing National Cancer Institute statistics, the FDA statement said that in the United States every year, about 21,700 people are diagnosed with multiple myeloma and 10,710 die from the disease.
Novartis is marketing the drug as Farydak. The company’s statement announcing approval said that ”as an HDAC [histone deacetylases] inhibitor, its epigenetic activity may help to restore cell function in multiple myeloma.”
Panobinostat, an orally administered histone deacetylase inhibitor, has been approved as a treatment for multiple myeloma, the first treatment in this class to be approved for this type of malignancy, the Food and Drug Administration announced on Feb. 23.
The approval is for use in combination with bortezomib and dexamethasone for treating patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. This is an accelerated approval, based on a surrogate endpoint considered “reasonably likely to predict clinical benefit to patients,” and the manufacturer is required by the FDA to conduct a confirmatory trial for full approval. The indications section of the prescribing information includes the following statement: “This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”
Originally, the manufacturer, Novartis Pharmaceuticals, filed for approval of panobinostat, combined with bortezomib (Velcade), a proteasome inhibitor, and dexamethasone, as a treatment for patients with multiple myeloma who had received at least one prior therapy, based on the results of the PANORAMA-1 (Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma) study. At a meeting in November 2014, the majority of the FDA’s Oncologic Drugs Advisory Committee voted that the benefits of treatment did not outweigh the risks for this indication, although panelists said that there was evidence that panobinostat had biologic activity against multiple myeloma and had an effect on PFS.
After the meeting, Novartis submitted more data that supported approval in the patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent, according to the FDA statement. Among 193 patients in the study who had received at least two other treatments that included bortezomib and an immunomodulatory agent, the median PFS was about 10.6 months among those who were treated with the three agents, vs. 5.8 months among those on bortezomib and dexamethasone only. The response rate was 59% among panobinostat-treated patients, vs. 41% of those on bortezomib and dexamethasone only.
This approval is “particularly important because it has been shown to slow the progression of multiple myeloma,” Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement. He referred to the novel mechanism of action of panobinostat as “making it a potentially attractive candidate agent for the treatment of multiple myeloma.”
The prescribing information includes a boxed warning that says severe diarrhea affected 25% of treated patients, and that treated patients have developed severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes. The drug is approved with a Risk Evaluation and Mitigation Strategy (REMS) addressing these risks.
The most common adverse events associated with panobinostat included diarrhea, fatigue, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting, and weakness; the most common laboratory abnormalities were hypophosphatemia, hypokalemia, hyponatremia, an increased creatinine level, thrombocytopenia, leukopenia, and anemia, according to the FDA statement.
Citing National Cancer Institute statistics, the FDA statement said that in the United States every year, about 21,700 people are diagnosed with multiple myeloma and 10,710 die from the disease.
Novartis is marketing the drug as Farydak. The company’s statement announcing approval said that ”as an HDAC [histone deacetylases] inhibitor, its epigenetic activity may help to restore cell function in multiple myeloma.”
Panobinostat, an orally administered histone deacetylase inhibitor, has been approved as a treatment for multiple myeloma, the first treatment in this class to be approved for this type of malignancy, the Food and Drug Administration announced on Feb. 23.
The approval is for use in combination with bortezomib and dexamethasone for treating patients with multiple myeloma who have received at least two prior regimens, including bortezomib and an immunomodulatory agent. This is an accelerated approval, based on a surrogate endpoint considered “reasonably likely to predict clinical benefit to patients,” and the manufacturer is required by the FDA to conduct a confirmatory trial for full approval. The indications section of the prescribing information includes the following statement: “This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.”
Originally, the manufacturer, Novartis Pharmaceuticals, filed for approval of panobinostat, combined with bortezomib (Velcade), a proteasome inhibitor, and dexamethasone, as a treatment for patients with multiple myeloma who had received at least one prior therapy, based on the results of the PANORAMA-1 (Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma) study. At a meeting in November 2014, the majority of the FDA’s Oncologic Drugs Advisory Committee voted that the benefits of treatment did not outweigh the risks for this indication, although panelists said that there was evidence that panobinostat had biologic activity against multiple myeloma and had an effect on PFS.
After the meeting, Novartis submitted more data that supported approval in the patients who have received at least two prior standard therapies, including bortezomib and an immunomodulatory agent, according to the FDA statement. Among 193 patients in the study who had received at least two other treatments that included bortezomib and an immunomodulatory agent, the median PFS was about 10.6 months among those who were treated with the three agents, vs. 5.8 months among those on bortezomib and dexamethasone only. The response rate was 59% among panobinostat-treated patients, vs. 41% of those on bortezomib and dexamethasone only.
This approval is “particularly important because it has been shown to slow the progression of multiple myeloma,” Dr. Richard Pazdur, director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research, said in the FDA statement. He referred to the novel mechanism of action of panobinostat as “making it a potentially attractive candidate agent for the treatment of multiple myeloma.”
The prescribing information includes a boxed warning that says severe diarrhea affected 25% of treated patients, and that treated patients have developed severe and fatal cardiac ischemic events, severe arrhythmias, and ECG changes. The drug is approved with a Risk Evaluation and Mitigation Strategy (REMS) addressing these risks.
The most common adverse events associated with panobinostat included diarrhea, fatigue, nausea, swelling in the arms or legs, decreased appetite, fever, vomiting, and weakness; the most common laboratory abnormalities were hypophosphatemia, hypokalemia, hyponatremia, an increased creatinine level, thrombocytopenia, leukopenia, and anemia, according to the FDA statement.
Citing National Cancer Institute statistics, the FDA statement said that in the United States every year, about 21,700 people are diagnosed with multiple myeloma and 10,710 die from the disease.
Novartis is marketing the drug as Farydak. The company’s statement announcing approval said that ”as an HDAC [histone deacetylases] inhibitor, its epigenetic activity may help to restore cell function in multiple myeloma.”