New FDA Approvals

These drugs were recently approved by the FDA:

Nelarabine (Arranon) by GlaxoSmithKline. The FDA has approved nelarabine (Arranon) to treat adults and children with T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), whose disease has not responded to or has relapsed following at least two chemotherapy regimens. Nelarabine, a cancer chemotherapy drug that kills cancer cells by blocking the cell’s ability to reproduce, is the first drug to treat this limited population of patients.

Nelarabine was approved under the FDA’s accelerated approval program. Evidence presented for the drug’s approval consisted of complete disappearance of cancer cells in some patients, although in most cases the cancer later returned. In those patients who responded to nelarabine, the disappearance of cancer cells was sometimes accompanied by return of normal blood cell counts. The drug’s sponsor will complete further studies to verify nelarabine’s clinical benefit. Nelarabine had also received orphan drug designation.

The safety and efficacy of this product were demonstrated in two clinical studies, one conducted in children and the other in adults. Both studies enrolled patients with relapsed or refractory T-ALL/T-LBL. All patients received nelarabine. Among the 39 pediatric patients treated, 23% had a complete disappearance of their cancer. Complete disappearance lasted from 3.3 to 9.3 weeks. Of the 28 adult patients treated, the rate of complete disappearance was 21% and lasted from four to more than 195 weeks.

Common side effects reported with nelara-bine treatment are fatigue, nausea, vomiting, and diarrhea.

New indication for erlotinib (Tarceva) by OSI Pharmaceuticals and Genentech. The FDA has approved erlotinib (Tarceva) in combination with gemcitabine chemotherapy for the treatment of advanced pancreatic cancer in patients who have not received previous chemotherapy.

Erlotinib, which targets the EGFR/HER1 pathway, is the first drug in a Phase III trial to have shown a significant improvement in overall survival when added to gemcitabine chemotherapy as initial treatment for pancreatic cancer, the drug’s sponsors say.

Erlotinib is a once-daily oral tablet already approved for use in patients with non-small cell lung cancer whose disease has progressed after one or more courses of chemotherapy. The FDA based its approval decision for erlotinib on results from a randomized double-blind, placebo-controlled Phase III clinical study of erlotinib, in combination with gemcitabine chemotherapy in patients with unresectable locally advanced or metastatic pancreatic cancer. The study met its primary endpoint of improving overall survival.

In the Phase III study in pancreatic cancer, the most common adverse events reported were fatigue, rash, nausea, anorexia, and diarrhea. In addition, severe and potential fatal adverse events included interstitial lung disease-like complications, myocardial infarction or ischemia, cerebrovascular accident, and microangiopathic hemolytic anemia with thrombocytopenia.

New indication for exemestane tablets (Aromasin) by Pfizer. The FDA has approved exemestane tablets (Aromasin) for adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer following two to three years of tamoxifen for a completion of five consecutive years of adjuvant hormonal therapy.

The approval was based on the Intergroup Exemestane Study (IES) which showed that patients who switched to exemestane after two to three years of tamoxifen, for a combined total of five years of therapy, had 31% more protection from cancer recurrence than those who remained on five years of tamoxifen therapy.

After the study was published in the New England Journal of Medicine, the American Society of Clinical Oncologists and the National Comprehensive Cancer Network updated their guidelines to support the use of a new switch regimen using exemestane adjuvant treatment.

The most common side effects for exemestane, which were mild to moderate, include hot flashes (21.2%), fatigue (16.1%), and arthralgia/bone pain (14.6%). Exemestane should not be administered to premenopausal women and women who are pregnant. Dose modifications should be considered for patients taking concomitant CYP3A4 inducers.

New formulation of lopinavir/ritonavir (Kaletra) by Abbott. The FDA has approved a new tablet formulation of Abbott’s HIV protease inhibitor (PI) lopinavir/ritonavir (Kaletra), which will allow adult patients to take fewer pills with or without food as part of their treatment regimen.

The FDA approval of the lopinavir/ritonavir tablet formulation was based on data from pharmacokinetic studies in 141 non-HIV-infected, healthy individuals. The studies demonstrated that lopina-vir/ritonavir tablets provide similar drug levels in the blood to the capsule formulation. In these studies, lopinavir/ritonavir tablets were generally well tolerated. Tablet benefits include:

  • Fewer tablets per dose as part of a treatment regimen in adults. While the total daily dose of lopinavir/ritonavir (800 mg lopinavir/200 mg ritonavir) is unchanged, the number of lopina-vir/ritonavir pills adult patients need to take is reduced from six capsules to four tablets per day.
  • Lopinavir/ritonavir tablets can be taken with or without food.
  • Lopinavir/ritonavir tablets do not need to be refrigerated before or after dispensing. Exposure to high humidity outside the original container for longer than two weeks is not recommended.

The new lopinavir/ritonavir tablets each contain 200 mg lopinavir and 50 mg ritonavir, and the old capsules each contain 133.3 mg lopinavir and 33.3 mg ritonavir. The film-coated tablets are similar in size to the capsules. The color of the new lopinavir/ritonavir tablets in the U.S. is yellow. The old lopinavir/ritonavir capsules are orange.

Taking lopinavir/ritonavir with certain drugs can cause serious problems or death. (See prescribing information for list.) Pancreatitis and liver problems, which can be fatal, have also been reported in patients receiving lopinavir/ritonavir. The most commonly reported side effects of moderate severity with lopinavir/ritonavir are abdominal pain, abnormal bowel movements, diarrhea, feeling weak or tired, headache, and nausea. Children taking lopinavir/ritonavir may sometimes get a skin rash.