Genomics News and Upcoming Events
- American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2013, 114th Annual Meeting, Indianapolis, Indiana.
March 6-9, 2013. Information and Registration
- A new HER2 blocker: FDA Approval of Pertuzumab, a humanized monoclonal antibody in combination with Trastuzumab and Docetaxel for HER2-positive metastatic breast cancer
On June 8, 2012, the FDA approved pertuzumab for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Pertuzumab also blocks other HER family members, including EGFR, HER3, and HER4, and is believed to complement HER2 inhibition.
The effectiveness and safety of pertuzumab was evaluated in a randomized trial in patients with HER2-positive breast cancer. Progression-free survival (PFS) was significantly improved in the pertuzumab plus trastuzumab and docetaxel arm (median: 18.5 months) compared to the placebo plus trastuzumab and docetaxel arm (median: 12.4 months), with a hazard ratio of 0.62 (95% CI: 0.51, 0.75; P<0.0001).
With the proposed dosing regimen (an initial dose of 840 mg followed by a maintenance dose of 420 mg every three weeks thereafter), the steady-state concentration of pertuzumab was reached after the first maintenance dose. Population PK analysis suggested no PK differences based on age or gender. No PK differences were observed between Japanese and non-Japanese populations. No dose adjustments based on body weight or baseline albumin level are needed.
No drug-drug interactions were observed between pertuzumab and trastuzumab, or between pertuzumab and docetaxel. Dose adjustments of pertuzumab are not needed in patients with mild or moderate renal impairment, and no large changes in the mean QT interval (i.e., greater than 20 ms) were detected for the labeled dosing regimen.
Anti-therapeutic antibodies (ATA) were detected in patients, but no known association with hypersensitivity reactions or anaphylaxis was determined, and the benefit of pertuzumab treatment seemed to be preserved within both ATA-positive and ATA-negative subgroups.
- Breakthrough therapy targeting mutation in the CFTR gene: FDA approves KalydecoTM (ivacaftor) tablets to treat rare form of cystic fibrosis
On January 31, 2012, FDA approved Kalydeco (ivacaftor) for the treatment of a rare form of cystic fibrosis (CF) in patients ages 6 years and older who have the specific G551D mutation in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. Kalydeco is an excellent example of the promise of personalized medicine.
Kalydeco is the first available treatment that targets the defective CFTR protein and improves its function, and as a result, improves lung function and other aspects of CF such as increasing weight gain. Kalydeco is not effective in CF patients with two copies of the F508del mutation in the CFTR gene, which is the most common mutation that results in CF.
Kalydeco is to be administered with fat-containing food at a dose of 150 mg twice-daily (every 12 hours). Selection of 150 mg twice-daily dose was supported by exposure-response analysis for efficacy endpoint.
Two 48-week, placebo-controlled clinical studies involving 213 patients, one in patients ages 12 years and older and another in patients ages 6 years to 11 years, were used to evaluate the safety and efficacy of Kalydeco in CF patients with the G551D mutation. In both studies, treatment with Kalydeco resulted in significant improvement in lung function.