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Pfizer Announces Submission of Palbociclib New Drug Application to the FDA

On August 18, 2014 Pfizer reported it has completed the submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for palbociclib (Press release Pfizer, AUG 18, 2014, View Source [SID:1234500708]). This NDA requests FDA approval of palbociclib, in combination with letrozole, for the treatment of postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease. The submission is based on the final results of PALOMA-1, a randomized, Phase 2 trial comparing palbociclib plus letrozole versus letrozole alone in this population of patients.

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Palbociclib received Breakthrough Therapy designation from the FDA in April 2013, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer. This designation was based on interim data from the PALOMA-1 trial.
The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing. Pfizer will communicate the Agency’s decision.

"Today’s submission marks an important milestone for Pfizer and palbociclib, and a potential advance for women with advanced breast cancer," said Garry Nicholson, President, Pfizer Oncology.

EISAI SUBMITS MARKETING APPROVAL APPLICATIONS FOR ANTICANCER AGENT LENVATINIB SIMULTANEOUSLY IN EUROPE AND U.S.

On August 18, 2014 Eisai reported that it has submitted applications to regulatory authorities in the U.S. and Europe (the FDA and EMA respectively) for marketing approval of its novel in-house developed anticancer agent lenvatinib mesylate (lenvatinib) as a treatment for progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC) (Press release Eisai, AUG 17, 2014, View Source [SID:1234500705]).

An application seeking marketing approval of lenvatinib for the indication of thyroid cancer was submitted in Japan on June 26, 2014. Lenvatinib was granted Orphan Drug Designation for thyroid cancer in Japan, Europe and the U.S. Lenvatinib was also granted an accelerated assessment in Europe by the EMA, as it is a new medicine expected to be of major public health interest, particularly from the viewpoint of therapeutic innovation.

Lenvatinib is an oral multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of several different RTKs including VEGFR, FGFR, PDGFRα, KIT and RET, involved in angiogenesis and tumor proliferation. This potentially makes lenvatinib a first-in-class treatment in thyroid cancer, especially given that it simultaneously inhibits the kinase activities of FGFR as well as VEGFR.

The applications submitted were based on a Phase III clinical study, known as the SELECT (Study of (E7080) LEnvatinib in Differentiated Cancer of the Thyroid) trial, which was a multicenter, randomized, double-blind, placebo-controlled study of lenvatinib in 392 patients with RR-DTC and radiographic evidence of disease progression within the prior 13 months (patients may have received ≤1 prior VEGFR-targeted therapies). The study was conducted by Eisai in cooperation with SFJ Pharma Ltd.

Compared to placebo, lenvatinib achieved a statistically significant improvement (Hazard Ratio (HR) 0.21, p<0.0001) in progression free survival (PFS), which was the primary objective of the study. The most common lenvatinib treatment-related adverse events (events with an incidence rate of at least 40%) were hypertension, diarrhea, decreased appetite, weight loss and nausea. The number of patients newly diagnosed with thyroid cancer in 2012 in the U.S. and Europe was estimated to be approximately 52,000 and 53,000, respectively. Although treatment is possible for most types of thyroid cancer, there are few treatment options available once thyroid cancer has progressed, therefore it remains a disease with significant unmet medical needs. Eisai is committed to exploring the potential clinical benefits of lenvatinib in order to further contribute to patients with cancer, including patients with thyroid cancer, and their families.

Lentigen Corporation announces Sale of Lentiviral Vector Manufacturing Business and Change of Name to Opus Bio, Inc.

On August 14, 2014 Lentigen Corporation reported the sale of its lentiviral vector manufacturing business and related assets to Miltenyi Biotec, who will operate through its newly formed, wholly-owned US subsidiary Lentigen Technology, Inc. based in Gaithersburg, MD (Press release Lentigen, AUG 14, 2014, View Source [SID:1234501087]).

In connection with the transaction, Lentigen Corporation has been renamed Opus Bio, Inc., and has been granted certain rights to deploy lentiviral technology in specified therapeutic indications, for which Lentigen Technology, Inc. shall be the preferred manufacturing supplier. These rights include specified CAR T-cell based therapies as well as specified therapies for single-gene diseases and disorders.

Chimeric antigen receptor T cell therapy (CAR+ T) technologies have made significant advances during the past several years, as evidenced by consistent clinical results reported by several academic teams. "We are pleased that Lentigen Corporation has been at the forefront of the lentiviral vector manufacturing innovation that has enabled these advances in the treatment of hematologic malignancies," said David Wetherell, Chairman of Lentigen Corporation. He added, "this transaction will provide Opus Bio with ongoing access to innovations in lentiviral vector and cell processing technologies, while allowing the company to commit further resources toward the advancement its research and clinical development programs."

Opus Bio intends to make further announcements on the progress of its therapeutic pipeline during the coming months.

Opus Bio is a clinical-stage biotechnology company committed to developing potentially transformative cell therapies for cancer and single gene disorders. The company is backed by Biomark Capital, a life sciences and healthcare investment firm with offices in Greenwich, CT and San Francisco, CA.

FDA approves Roche's Avastin plus chemotherapy for treatment of advanced cervical cancer

On August 14, 2014 Roche reported that the U.S. Food and Drug Administration (FDA) approved Avastin (bevacizumab) in combination with paclitaxel and cisplatin or paclitaxel and topotecan for the treatment of women with persistent, recurrent or metastatic carcinoma of the cervix (Press release Hoffmann-La Roche, AUG 14, 2014, View Source [SID:1234500723]).

"With this approval, women with advanced cervical cancer now have the option of Avastin plus chemotherapy to help them live longer than with chemotherapy alone," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. "Cervical cancer is most commonly diagnosed in women between the ages of 35 and 44, and until today, chemotherapy was the only approved treatment option for women whose cancer recurred, persisted or spread."

With this approval in advanced cervical cancer, Avastin is approved in the United States to treat five distinct tumour types. The approval in advanced cervical cancer was based on the GOG-0240 study.

About the GOG-0240 study

GOG-0240 is an independent, National Cancer Institute (NCI)-sponsored study of the Gynecologic Oncology Group (GOG), which assessed the efficacy and safety profile of Avastin plus chemotherapy (paclitaxel and cisplatin or paclitaxel and topotecan) in women with persistent, recurrent or metastatic cervical cancer. Study data from 452 women showed:

The study met its primary endpoint of improving overall survival (OS) with a statistically significant 26 percent reduction in the risk of death for women who received Avastin plus chemotherapy compared to those who received chemotherapy alone (median OS: 16.8 months vs. 12.9 months; Hazard Ratio (HR)=0.74, p=0.0132).
The study showed women who received Avastin plus chemotherapy had a significantly higher rate of tumor shrinkage (objective response rate, ORR) compared to chemotherapy alone (45 percent [95% CI: 0.39%-0.52%] vs. 34 percent [95% CI 0.28%-0.40%]).
Hypertension (high blood pressure) of Grade 2 or higher was significantly more common with Avastin-containing regimens (29 percent vs. 6 percent), but no patients discontinued Avastin because of hypertension. Grade 3 or higher thrombosis (blood clots) were significantly increased with the Avastin-containing regimens (8.3 percent vs. 2.7 percent). Gastrointestinal-vaginal fistulas (abnormal passage from one part of the body to another) occurred in 8.2 percent of patients receiving Avastin-containing regimens compared to 0.9 percent with chemotherapy alone, all of whom had a history of prior pelvic radiation. Patients who develop these fistulas may require additional surgery. Additionally, 1.8 percent of Avastin treated patients and 1.4 percent of control patients were reported to have had non-gastrointestinal fistulas in the vaginal, vesical, or female genital tract. Gastrointestinal perforations (a hole in the stomach or intestine) also occurred in 3.2 percent of Avastin-treated patients, all of whom had a history of prior pelvic radiation.
There was no increase in treatment-related deaths in the Avastin plus chemotherapy arm as compared to the chemotherapy alone arm.

Polmacoxib Demonstrates Prevention And Treatment Effects In Colorectal Cancer

On August 13, 2014 CrystalGenomics, Inc. (www.cgxinc.com), a clinical stage biopharmaceutical company headquartered in Korea, has reported a positive outcome from an investigational preclinical research conducted, in part, at the University of Texas MD Anderson Cancer Center by Dr. Raymond N. DuBois’ laboratory where the purpose of the research was to explore the potential anti-tumor effects of polmacoxib (formerly CG100649), CrystalGenomics’ novel Non-Steroidal Anti-Inflammatory Drug (NSAID) candidate with its NDA pending for an approval by the MFDS of South Korea for the relief of signs and symptoms of osteoarthritis (Press release, CrystalGenomics, AUG 13, 2014, View Source;id=1314&page=5&num=83&nowpos=646&type=&sermun=&qu=&tb_name=eng_news&rt_page=/en/news/news.php [SID1234539169]). On December 1, 2012 Dr. DuBois Laboratory on Inflammation and Cancer relocated to the Biodesign Institute at Arizona State University in Tempe, Arizona.

The preclinical research was designed to examine the possible use of polmacoxib for both prevention and treatment of colorectal cancer (CRC). For the first part of the research, a premalignant mouse model was used to determine efficacy of polmacoxib in polyp reduction and it was observed that polmacoxib was effective in reducing the polyp number and size in both the small and large intestines in the prevention study. In the treatment study, polmacoxib demonstrated significant growth suppression of established polyps in the small intestine and also, reduction of the polyp growth in the colon. These results suggested that polmacoxib would be effective in prevention and treatment of polyps.

The second part of the study examined polmacoxib’s ability to suppress growth of human colorectal carcinoma in the subcutaneous and orthotopic xenograft mouse models. With the subcutaneous model, it was observed that treatment with polmacoxib lead to significant reduction of subcutaneous tumor growth. Similarly, it was observed that treatment with polmacoxib inhibited CRC growth in an orthotopic xenograft mouse model. Overall results from both mouse models lead to a conclusion that polmacoxib could be effective in not only prevention of CRC through reduction of premalignant polyp number and size but also, treatment of CRC by suppressing growth of malignant colonic lesions in humans. More detailed results of this preclinical research have been published in the August edition of the Investigational New Drugs Journal.

The preclinical research was conducted at the laboratory of Dr. Raymond DuBois, an internationally renowned investigator and researcher in the field of cancer, especially in the link between colorectal cancer, arthritis drugs and the cyclooxygenase-2 (COX-2) enzyme. His group was the first to demonstrate elevation of COX-2 expression in colorectal adenomas and carcinomas. Dr. DuBois had previously served as the president of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), provost and executive vice president of MD Anderson and currently is the Executive Director of the Biodesign Institute at Arizona State University (View Source).

Chairman & CEO of CrystalGenomics, Dr. Joong Myung Cho said, "We are extremely pleased with the outcome of this preclinical study as it provides tremendous potential for polmacoxib to become a widely prescribed drug for not only pain & inflammation associated conditions but also for oncology. It was quite exciting to work with a world renowned cancer center and to have the research led by a premier investigator. Although further clinical studies will be required for the oncology applications should we choose to pursue that path, we believe that polmacoxib is capable of making a significant contribution in the improvement of human health as there still are great unmet medical needs in the both areas of osteoarthritis and colorectal cancer."