On April 6, 2014 Pfizer reported detailed results from the PALOMA-1 study (NCT00721409), a randomized Phase 2 study of palbociclib (PD-0332991) in combination with letrozole (Press release Pfizer, APR 6, 2014, View Source [SID:1234500368]). PALOMA-1 achieved its primary endpoint by significantly prolonging progression-free survival (PFS) compared with letrozole alone in post-menopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) locally advanced or metastatic breast cancer. For women treated with the combination of palbociclib plus letrozole, the median PFS was 20.2 months, a statistically significant improvement compared to the 10.2 months of PFS in women who received letrozole alone (HR=0.488 [95% CI: 0.319, 0.748]; p=0.0004). These data at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2014 in San Diego (Abstract #CT101).
Final results for the secondary efficacy endpoints of duration of treatment and clinical benefit rate demonstrated superiority in the palbociclib plus letrozole arm compared to the letrozole-only arm. Per the PALOMA-1 trial protocol, an initial assessment of overall survival (OS), a secondary endpoint, was also performed. Based on the events at the time of the assessment, a median OS of 37.5 months was observed in the combination arm versus 33.3 months for those who received letrozole alone, a difference of 4.2 months (HR = 0.813, 95% CI: 0.492, 1.345). This OS observation at the time of final PFS analysis was not statistically significant. A follow-up OS analysis will be conducted following the accrual of additional events.
The combination of palbociclib and letrozole was generally well-tolerated and the safety profile of the combination was consistent with previously reported data. The most common adverse events in the palbociclib plus letrozole arm were neutropenia (a decrease of the neutrophil count), leukopenia, fatigue and anemia. The neutropenia observed with the combination in this study was non-cumulative and clinically manageable. No cases of febrile neutropenia were reported in either arm of the study. Neutropenia is an on-target, anti-proliferative side effect of palbociclib and signifies inhibition of CDK4 and its effect on bone marrow.
Palbociclib received Breakthrough Therapy designation from the United States Food and Drug Administration (FDA) in April 2013, for the initial treatment of women with advanced or metastatic ER+, HER2- breast cancer. This designation was based on interim data from the PALOMA-1 trial. Pfizer continues to work with the FDA and other regulatory authorities to define the appropriate regulatory path forward for palbociclib.
Halozyme Announces Temporary Halt Of Phase 2 Trial Enrollment And Dosing For PEGPH20
On April 4, 2014 Halozyme Therapeutics announced that as a result of a recommendation received yesterday from an independent Data Monitoring Committee (DMC), it is temporarily halting patient enrollment and dosing of PEGPH20 in an ongoing Phase 2 trial (Study 202/NCT01839487) evaluating PEGPH20 in patients with pancreatic cancer (Press release Halozyme, APR 4, 2014, View Source [SID:1234500367]). The DMC is assessing clinical data that indicates a possible difference in the thromboembolic event rate between the group of patients treated with PEGPH20, nab-paclitaxel and gemcitabine versus the group of patients treated with nab-paclitaxel and gemcitabine without PEGPH20. The Company is halting enrollment and dosing of PEGPH20 as precautionary actions while the DMC’s full evaluation of the data is ongoing.
Amgen Provides Update On Phase 3 Study Of Talimogene Laherparepvec In Patients With Metastatic Melanoma
On April 4, 2014 Amgen reported top-line results from the primary overall survival (OS) analysis of a Phase 3 trial in melanoma, which evaluated the efficacy and safety of talimogene laherparepvec for the treatment of unresected stage IIIB, IIIC or IV melanoma compared to treatment with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF) (Press release Amgen, APR 4, 2014, View Source;p=RssLanding&cat=news&id=1915897 [SID:1234500366]). Results showed that, while the primary end point of durable response rate was met (as previously reported), the secondary endpoint of OS was not met, although there was a strong trend in favor of talimogene laherparepvec (p=0.051). The estimated OS hazard ratio and improvement in median OS were similar to what was previously reported at the interim OS analysis.
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors and to initiate an immune response to target cancer that has metastasized, or spread to other areas of the body.
The global, randomized, open-label Phase 3 trial enrolled patients with unresected stage IIIB, IIIC or IV melanoma. Patients were randomized 2:1 to receive either talimogene laherparepvec every two weeks through direct tumor injection or GM-CSF subcutaneously for the first 14 days of each 28-day cycle, for up to 18 months.
The most frequent adverse events observed in this trial were fatigue, chills and pyrexia. The most common serious adverse events include disease progression, cellulitis and pyrexia.
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Amgen ends marketing agreement with GSK for osteoporosis drug
On April 3, 2014 Amgen reported that it would end an agreement with GlaxoSmithKline Plc for the marketing of its osteoporosis drug in some regions outside the United States (Press release, Amgen, APR 3, 2014, View Source [SID:1234502170]).
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Amgen said it would take over the marketing of the drug, sold under the brand name Prolia, in most areas under the agreement, including the European Union, Switzerland, Norway, Russia and Mexico, by Dec. 31.
GSK will continue to market the drug in Australia, Amgen said in a regulatory filing.
"GSK and Amgen have reached a mutual agreement to end their existing agreement…," a GSK spokesman said in an emailed statement, adding, "This new arrangement will allow GSK to increase focus on executing important new product launches over the next few years."
Amgen said it would pay GSK $275 million over the rest of the year and reimburse the British drugmaker $15 million for costs incurred during the transition period.
Prolia generated worldwide sales of $744 million in 2013, a 58 percent increase from a year earlier. (link.reuters.com/mux28v)
According to the agreement signed in July 2009, Amgen retained the rights to market the drug in the United States and Canada as a treatment for osteoporosis and other conditions and as a treatment for cancer in Europe, Australia, New Zealand and Mexico.
Amgen also said on Thursday that GSK would continue to market the drug as a treatment for conditions other than osteoporosis in countries such as China, Brazil, India and South Korea.
GSK holds the marketing rights in these regions until 2024, according to Amgen’s annual report.
Amgen is developing the drug in late-stage studies as a treatment for other forms of osteoporosis, including glucocorticoid-induced osteoporosis and male osteoporosis.
The company is also testing the drug, denosumab, as a treatment for cancer-related bone damage.
Denosumab is sold under the brand name Prolia as a treatment for three conditions, including postmenopausal osteoporosis in women at high risk of fracture.
The drug is approved in the United States as a treatment for giant cell tumor of the bone and is sold under the brand name Xgeva. (Reporting by Vrinda Manocha in Bangalore; Editing by Simon Jennings)
ASTELLAS ANNOUNCES MARKETING AUTHORISATION APPLICATION FOR XTANDI™ (ENZALUTAMIDE) FOR CHEMOTHERAPY-NAÏVE METASTATIC PROSTATE CANCER (pdf 83KB)
On April 3, 2014 Astellas Pharma announces the submission of a variation to amend the Marketing Authorisation Application for XTANDI (enzalutamide) capsules for the treatment of adult men with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy and in whom chemotherapy is not yet clinically indicated (Press release Astellas, APR 3, 2014, View Source [SID:1234500365]). Enzalutamide is currently approved in Europe for the treatment of adult men with mCRPC whose disease has progressed on or after docetaxel chemotherapy.