Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced updates to its development program for IPI-926, including that the company has completed enrollment of its Phase 2 trial of IPI-926 in patients with previously untreated pancreatic cancer.
The double-blind, placebo-controlled trial of 122 randomized patients is designed to compare IPI-926 in combination with gemcitabine (also known as Gemzar®) to treatment with placebo and gemcitabine. The primary endpoint of the trial is overall survival. Infinity initiated this Phase 2 trial in February 2011.
“We are pleased to reach our target enrollment in this trial ahead of schedule, underscoring the urgent need for new treatment options that can make a meaningful difference for patients with pancreatic cancer,” stated Robert Ross, M.D., vice president, clinical development at Infinity. “I would like to thank the patients and families for their participation, as well as our investigators for their support and commitment to developing new agents for the treatment of pancreatic cancer.”
IPI-926 is a novel, oral, small molecule that inhibits Smoothened, a key component of the Hedgehog pathway. In preclinical models of pancreatic cancer, the Hedgehog pathway signals from the tumor to the surrounding environment to create a thick, fibrous tissue that provides support for tumor growth and prevents chemotherapy from reaching the tumor effectively.1,2 Inhibiting Smoothened with IPI-926 may represent a fundamentally new approach to treating pancreatic cancer by depleting the fibrous tissue and facilitating the delivery of chemotherapy to the tumor.
“IPI-926 as part of combination therapy may represent a new approach to treating pancreatic cancer by inhibiting the Hedgehog pathway and potentially improving delivery of chemotherapy to the tumor,” said Charles Fuchs, M.D., MPH, Director, Gastrointestinal Cancer Center at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School. “Clinical trials evaluating possible new treatments for pancreatic cancer, like this study with IPI-926, will hopefully lead to advances with the potential to improve survival for patients.”
In June 2011, researchers presented data from a Phase 1b trial evaluating once daily, oral administration of IPI-926 at escalating doses in combination with the standard dose of gemcitabine (1000 mg/m2) administered intravenously once weekly for three weeks with one week of rest in previously untreated patients with metastatic pancreatic cancer. A partial response was observed in five of the 16 patients, for a 31 percent response rate. The historic overall response rate to gemcitabine is less than 10 percent.3,4 Infinity continues to follow patients still enrolled in the trial and intends to report additional data from the Phase 1b trial at a future medical meeting.
“We look forward to obtaining the results from the ongoing trial in pancreatic cancer, which will inform our Phase 3 development plans,” stated Pedro Santabárbara, M.D., Ph.D., chief medical officer at Infinity. “Beyond pancreatic cancer, we are focused on advancing IPI-926 in Phase 2 trials in myelofibrosis and chondrosarcoma, as well as exploring a range of indications through investigator sponsored trials.”
Additional IPI-926 Program Updates
Infinity today also provided the following IPI-926 program updates:
- Phase 2 Trial in Myelofibrosis Initiated: Infinity is now actively enrolling patients in a Phase 2 exploratory clinical trial in up to 45 patients with myelofibrosis. The single-arm Phase 2 trial is designed to evaluate the safety and efficacy of IPI-926 administered orally once daily. The primary endpoint of the trial is hematologic response rate according to the International Working Group Criteria.
- Data of IPI-926 in Preclinical Models of Pancreatic Cancer to Be Presented at Upcoming Scientific Meetings: Infinity scientists will present preclinical data of IPI-926 in combination with nab-paclitaxel (also known as Abraxane®) in a xenograft model of pancreatic cancer, providing further rationale for evaluating IPI-926 in combination with chemotherapy in pancreatic cancer. The preclinical data will be presented at the upcoming American Association for Cancer Research (AACR) Tumor Microenvironment Complexity Meeting being held November 3 - 6, 2011, in Orlando, FL.
In addition, Infinity scientists will present data of IPI-926 in a preclinical model of pancreatic cancer liver metastasis at the upcoming AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics being held November 12 - 16, 2011, in San Francisco.
The company is also continuing to enroll patients in its Phase 2 trial of IPI-926 in patients with chondrosarcoma, a rare, life-threatening cancer of the cartilage. This randomized, double-blind trial is designed to compare the safety and efficacy of IPI-926 to matching placebo in patients with metastatic or locally advanced, inoperable chondrosarcoma. The trial is designed to enroll over 100 patients and is being conducted at approximately 50 sites worldwide.
About Pancreatic Cancer
Pancreatic cancer is the fourth leading cause of cancer death in the U.S., and it is estimated that more than 43,000 people are diagnosed with pancreatic cancer in the U.S. annually.5 Notoriously difficult to treat, pancreatic cancer has the lowest survival of all major cancers. The one-year survival rate for pancreatic cancer is 25 percent and the five-year survival rate is just six percent. The average life expectancy for patients with metastatic disease is three to six months. Unfortunately, pancreatic cancer is one of the few cancers for which the survival rate has not improved substantially over nearly 40 years.6
Myelofibrosis, an incurable malignancy of the bone marrow, is characterized by the replacement of normal bone marrow by fibrotic tissue and the production of blood cells in other organs, such as the spleen and liver. The primary manifestations of myelofibrosis are severe anemia resulting in weakness and fatigue, as well as massive enlargement of the spleen (splenomegaly) and liver (hepatomegaly), which result in abdominal pain and ultimately liver failure. The five-year survival rate for myelofibrosis is approximately 40 percent.7 There are limited treatment options for patients with myelofibrosis, and there are no approved therapeutic agents that directly target the fibrosis that underlies this disease.
Chondrosarcoma is a rare, life-threatening, cancer of the cartilage. In the U.S., chondrosarcoma accounts for approximately 30 percent of the 2,800 new cases of primary bone and joint cancers diagnosed each year.5 The most common locations for chondrosarcoma tumors to develop are the legs, arms or pelvis. Chondrosarcoma predominantly affects middle-aged and older adults, usually occurring in patients over 40 years old, with the incidence gradually increasing up to age 75.8,9 Chondrosarcomas are largely resistant to chemotherapy and radiotherapy, and the standard therapeutic strategy is surgery. For patients with metastatic disease or who are not candidates for surgery, no treatment has been shown to be effective and there is no established standard of care.
About Infinity Pharmaceuticals, Inc.
Infinity is an innovative drug discovery and development company seeking to discover, develop and deliver to patients best-in-class medicines for difficult-to-treat diseases. Infinity combines proven scientific expertise with a passion for developing novel small molecule drugs that target emerging disease pathways. Infinity’s programs in the inhibition of the Hedgehog pathway, the Hsp90 chaperone system, phosphoinositide-3-kinase and fatty acid amide hydrolase are evidence of its innovative approach to drug discovery and development. For more information on Infinity, please refer to the company’s website at www.infi.com.
Forward Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include those regarding the potential utility of Hedgehog pathway inhibition and IPI-926 in addressing cancer, the reporting of additional data from the Phase 1b trial of IPI-926 in pancreatic cancer at a future medical meeting, the presentation of preclinical data of IPI-926 in combination with nab-paclitaxel at the AACR Tumor Microenvironment Complexity Meeting, and the presentation of preclinical data of IPI-926 in a model of pancreatic cancer liver metastasis at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in 2011. Such statements are subject to numerous factors, risks and uncertainties that may cause actual events or results to differ materially from the company’s current expectations. For example, there can be no guarantee that IPI-926 will successfully complete necessary preclinical and clinical development phases or that Infinity’s strategic alliance with Mundipharma International Corporation Ltd. will continue for its expected term or that it will fund Infinity’s programs as agreed. Management’s expectations could also be affected by risks and uncertainties relating to: results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Infinity’s ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures, including in connection with business development activities; and Infinity’s ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing. These and other risks which may impact management’s expectations are described in greater detail under the caption “Risk Factors” included in Infinity’s quarterly report on Form 10-Q filed with the Securities and Exchange Commission on August 9, 2011. Any forward-looking statements contained in this press release speak only as of the date hereof, and Infinity expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.
Abraxane® is a registered trademark of Celgene Corporation, and Gemzar® is a registered trademark of Eli Lilly and Company.
1 Olive KP, Jacobetz MA, Davidson CJ, Gopinathan A, McIntyre D, Honess D, et al. Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer. Science 2009; 324(5933):1457-61.
2 Bailey JM, Swanson BJ, Hamada T, Eggers JP, Singh PK, Caffery T, et al. Sonic hedgehog promotes desmoplasia in pancreatic cancer. Clin Cancer Res. 2008;14(19):5995-6004.
3 Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: A phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2007; 25:1960-6.
4 Seitz JF, Dahan L, Ries P. Pemetrexed in pancreatic cancer. Oncology 2004; 18(13 Suppl 8):43-7.
5 Cancer Facts and Figures 2011, American Cancer Society. Last accessed September 26, 2011.
6 Pancreatic Cancer Action Network. Last accessed October 6, 2011.
7 Rupoli S, Da Lio L, Sisti S, Campanati G, Salvi A, Brianzoni MF, et al. Primary myelofibrosis: A detailed statistical analysis of the clinicopathological variables influencing survival. Ann Hematol. 1994; 68(4):205-12.
8 Dorfman HD, Czerniak B, Kotz R,, Vanel D, Park YK, Unni KK. WHO classification of tumours of bone: Introduction. In: Fletcher CDM. Unni KK, Mertens F.eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon, France: IARC Press; 2002.
9 Yasko AW, Chow W, Fressica D. Bone Sarcomas. In: Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ, eds. Cancer Management: A Multidisciplinary Approach (ed 12): CMPMedicas LLC; 2008.