Synribo approved for CML Abraxane for NSCLC

November 2012, Vol 3, No 8 - FDA Approvals, News & Updates


?Synribo Approved for Chronic Myelogenous Leukemia
The US Food and Drug Admini­s­tration (FDA) approved omacetaxine mepesuccinate (Synribo; Teva Phar­ma­­ceutical) to treat adults with chron­ic myelogenous leukemia (CML), a he­matologic disease. An estimated 5430 Americans will be diagnosed with CML in 2012, according to the Na­tional Institutes of Health.

“Today’s approval provides a new treatment option for patients who are resistant to or cannot tolerate other FDA-approved drugs for chronic or accelerated phases of CML,” said Richard Pazdur, MD, Director of the FDA’s Office of Hematology and Oncology Products, noting that this is the second drug to be approved for CML in the past 2 months. In September, bosutinib (Bosulif; Pfizer) received FDA approval for patients with chronic-, accelerated-, or blast-phase Philadelphia chromosome–positive (Ph+) CML who are resistant to or who cannot tolerate other therapies.

Synribo is intended to be used in patients whose disease has progressed after treatment with ≥2 tyrosine kinase inhibitor (TKI) agents, currently the mainstay of therapy for CML.

Omacetaxine mepesuccinate blocks certain proteins that promote the development of cancerous cells. It is injected subcutaneously twice daily for 14 consecutive days over a 28-day cycle, until hematologic response is observed. The drug is then administered twice daily for 7 consecutive days over a 28-day cycle, and continues to be used as long as the patient shows clinical benefit from this therapy.

The FDA approved omacetaxine mepesuccinate under the agency’s accelerated approval program, which allows the agency to approve a drug deemed necessary for a serious disease, based on data from clinical trials showing that the drug has an effect on a surrogate end point that is likely to predict a clinical benefit to patients, to accelerate the access of patients to this therapy until additional clinical evidence is available. In addition, this drug received an orphan drug designation, because it is designated for the treatment of CML, which is considered a relatively rare disease.

The effectiveness of omacetaxine mepesuccinate was evaluated using a combined cohort of patients whose disease progressed after previous treatment with ≥2 TKIs. All patients re­ceived omacetaxine mepesuccinate in this evaluation.
The drug’s effectiveness in chronic-phase CML was demonstrated by a reduction in the percentage of cells expressing the Ph+ genetic mutation found in the majority of patients with CML. Of the 76 patients with chronic-phase CML, 14 patients (18.4%) achieved a reduction in Ph+ expression in an average of 3.5 months. The median duration of the reduction was 12.5 months.

In patients with accelerated-phase CML, the effectiveness of omacetaxine mepesuccinate was determined by the number of patients whose white blood cell counts were normalized or who had a major hematologic response (ie, no evidence of CML). Among the 35 patients with this type of CML, 5 patients (14.3%) achieved a major hematologic response in an average of 2.3 months. The response lasted a median of 4.7 months.

The most common side effects reported during clinical studies with omacetaxine mepesuccinate include thrombocytopenia, anemia, neutropenia (which may lead to febrile neutropenia), diarrhea, nausea, weakness and fatigue, injection site reaction, and lymphopenia. (October 26, 2012)

Abraxane Receives a New Indication for First-Line Therapy of NSCLC
The FDA approved a new indication for paclitaxel protein-bound particles for injection (Abraxane; Celgene Corporation) for the first-line treatment of locally advanced or metastatic non–small-cell lung cancer (NSCLC), in combination with carboplatin, for patients who are not candidates for curative surgery or radiation therapy.

“Non–small cell is the most common type of lung cancer, the leading cause of cancer death in the United States,” said Mark A. Socinski, MD, Director, Lung Cancer Section, Division of Hematology/Oncology, University of Pittsburgh, and lead investigator of phase 2 and phase 3 clinical trials of paclitaxel protein-bound particles in patients with lung cancer. “The FDA approval of Abraxane…offers an important new treatment option for all types of non–small-cell lung cancer patients, in an area that has seen few treatment advancements in recent years.”

The FDA approval of this new indication for paclitaxel protein-bound particles is based on the results of a phase 3, multicenter, open-label study of patients with advanced NSCLC who were randomized to paclitaxel protein-bound particles 100 mg/m2 weekly plus carboplatin (area under the curve [AUC] = 6) every 3 weeks (n = 521) or to generic paclitaxel 200 mg/m2 every 3 weeks plus carboplatin (AUC = 6; n = 531). Overall response rate (ORR)—the primary end point—was significantly higher with protein-bound paclitaxel particles compared with generic paclitaxel (33% vs 25%, respectively).

In addition, paclitaxel protein-bound particles demonstrated a higher ORR for squamous-cell carcinoma compared with paclitaxel (41% vs 24%, respectively) and for large-cell carcinoma (33% vs 15%, respectively).

Paclitaxel protein-bound particles achieved ORR that was similar to generic paclitaxel in patients with carcinoma or adenocarcinoma (26% vs 27%, respectively).

The most common (≥20%) adverse reactions reported with paclitaxel protein-bound particles in combination with carboplatin for NSCLC are anemia, neutropenia, thrombocytopenia, alopecia, peripheral neuropathy, nausea, and fatigue.

Paclitaxel protein-bound is already approved for the treatment of patients with metastatic breast cancer whose disease has progressed after therapy with or who did not respond to therapy with standard combination che­mo­­therapy. In addition, in early results (released November 7) from a phase 3 clinical trial, paclitaxel protein-bound particles in combination with gemcitabine showed significant improvement in overall survival in patients with pancreatic cancer compared with gemcitabine alone; complete results are expected in January. (October 11, 2012)