Infinity Reports New Data from Phase 1b Trial of Saridegib in Patients with Pancreatic Cancer at ASCO-GI
– Infinity to Review Saridegib Development Program on January 31, 2012, in New York City –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan 20, 2012 - Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) today announced updated data from the Phase 1b portion of an ongoing Phase 1b/2 clinical trial of saridegib (also known as IPI-926) in combination with the chemotherapy gemcitabine in patients with previously untreated, metastatic pancreatic cancer. These findings were presented during a poster session at the American Society of Clinical Oncology's 2012 Gastrointestinal Cancers Symposium (ASCO-GI) in San Francisco (Abstract #213) and support the ongoing Phase 2, double-blind, randomized, placebo-controlled trial comparing saridegib in combination with gemcitabine to placebo and gemcitabine. In October 2011, Infinity announced the completion of enrollment in the Phase 2 portion of the trial, and the company expects to report topline Phase 2 data in the second half of 2012. The primary endpoint of the Phase 2 portion of the trial is overall survival.
Data from the Phase 1b, open-label study in 16 patients showed that saridegib in combination with gemcitabine was well-tolerated and clinically active. As previously reported, the recommended Phase 2 dose of saridegib in combination with gemcitabine was established at 160 mg administered orally once daily, which is the maximum tolerated dose of saridegib when administered as a single agent. The adverse events observed were consistent with the known safety profile of each agent. In addition, partial responses were observed in five of 16, or 31 percent, of patients treated at three different dose levels of saridegib. New data reported today showed that median progression-free survival was 7.6 months (95 percent confidence interval (CI): 3.5 - 8.7 months) and median overall survival was 10.2 months (95 percent CI: 5.7 - 12.3 months).
“Pancreatic cancer has the lowest survival rate among all the major cancers, and new treatments that can improve survival rates are desperately needed,” stated Charles Fuchs, M.D., MPH, director, Gastrointestinal Cancer Center at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School. “I look forward to seeing the results from the ongoing Phase 2 trial.”
Saridegib 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 saridegib may represent a fundamentally new approach to treating pancreatic cancer by depleting the fibrous tissue and improving blood flow, thereby facilitating the delivery of chemotherapy to the tumor.
“Acknowledging the limitations of assessing progression-free and overall survival in a small, single-arm Phase 1b trial, we are encouraged by these data and hope to confirm these results in our ongoing Phase 2, double-blind, randomized, placebo-controlled trial,” stated Pedro Santabárbara, M.D., Ph.D., chief medical officer at Infinity. “We are also continuing to develop saridegib in additional indications, including myelofibrosis and chondrosarcoma, in which Hedgehog pathway inhibition could offer a new approach to treating cancers for which current therapeutic options are limited.”
Trial Design and Results
The Phase 1b, single-arm trial evaluated once daily, oral administration of saridegib 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. The primary goal of the study was to evaluate the safety and pharmacokinetics of saridegib in combination with gemcitabine and to determine the recommended dose for the ongoing Phase 2 study. The clinical activity of escalating doses of saridegib was also evaluated. In the trial, 16 patients received doses of saridegib ranging from 110 mg to 160 mg.
The combination of saridegib and gemcitabine was well-tolerated, and adverse events were consistent with the known tolerability profile of each agent. The most commonly observed adverse events were Grades 1 and 2. The most common Grade 3 or 4 events were neutropenia and thrombocytopenia. No pharmacokinetic interactions were observed between saridegib and gemcitabine.
Five partial responses were documented among the 16 patients entered in the trial. Median progression-free survival was 7.6 months (95 percent CI: 3.5 - 8.7 months) and median overall survival was 10.2 months (95 percent CI: 5.7 - 12.3 months).
Histological evaluation of patient tissues showed evidence of Hedgehog signaling in pancreatic cancer metastases. In addition, evidence of fibrosis was observed in liver metastases. Taken together, these histological data provide further rationale for developing saridegib in metastatic pancreatic cancer.
As previously reported, the recommended Phase 2 dose of saridegib in combination with gemcitabine was determined to be 160 mg administered orally once daily, which is the same as the single agent Phase 2 dose of saridegib.
A copy of the Phase 1b data presented at ASCO-GI can be obtained by visiting https://ipiweb01.ipi.com/Posters/PosterRequest.aspx?id=2.
Infinity to Review Saridegib Development Program on January 31, 2012 in New York City
On January 31, 2012, Infinity will discuss its research and development of saridegib, including the company's science and supporting rationale for the clinical development of saridegib along with the anticipated milestones for this program in the second half of 2012. A brief summary of the Phase 1b data of saridegib presented at ASCO-GI will also be included. The event will be held from 10:00 a.m. to 12:00 p.m. EST at the Hotel Sofitel New York City.
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.3 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.4
Saridegib is currently being evaluated in three Phase 2 trials: 1) in combination with gemcitabine in previously untreated patients with metastatic pancreatic cancer; 2) as a single agent in patients with myelofibrosis; and 3) as a single agent in patients with chondrosarcoma. Saridegib was well-tolerated and showed clinical activity in a Phase 1b trial in patients with metastatic pancreatic cancer and in a Phase 1 trial in patients with advanced solid tumors, including a cohort of patients with basal cell carcinoma. These clinical trials build upon a robust set of supporting data that provide a strong rationale for evaluating the potential of saridegib for treatment across a broad range of cancers.
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 focused on the inhibition of the Hedgehog pathway, heat shock protein 90, 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.
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 therapeutic potential of saridegib and of Hedgehog pathway inhibition and Smoothened inhibition, the expectation that Infinity will report top-line data from the Phase 2 portion of its Phase 1b/2 clinical trial of saridegib in combination with gemcitabine in patients with pancreatic cancer during the second half of 2012, and the expectation that in January 2012 Infinity will review the research and development of saridegib, including science and supporting rationale for clinical development and anticipated milestones for the program in the second half of 2012. 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 Infinity's strategic alliance with Mundipharma will continue for its expected term or that it will fund Infinity's programs as agreed, that any product candidate Infinity is developing will successfully complete necessary preclinical and clinical development phases, that the results of later clinical trials will confirm positive results from earlier preclinical studies or clinical trials, or that development of any of Infinity's product candidates will continue. Further, there can be no guarantee that any positive developments in Infinity's product portfolio will result in stock price appreciation. Management's expectations could also be affected by risks and uncertainties relating to: Infinity's 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; development of agents by Infinity's competitors for diseases in which Infinity is currently developing its product candidates; 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 for the quarter ended September 30, 2011 filed with the Securities and Exchange Commission on November 8, 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.
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 Cancer Facts and Figures 2011, American Cancer Society. Last accessed January 4, 2012.
4 Pancreatic Cancer Action Network. Last accessed October 6, 2011.
Posted: January 2012