SAN DIEGO, Sept. 30, 2013 /PRNewswire/ -- Halozyme Therapeutics, Inc. (NASDAQ: HALO) today announced mature patient progression free survival (PFS) and ongoing overall survival (OS) data from a Phase 1b trial of PEGPH20 (PEGylated Recombinant Human Hyaluronidase) in combination with gemcitabine for the treatment of patients with stage IV metastatic pancreatic cancer. In the trial, both PFS and OS data suggest a potential clinical benefit of using PEGPH20 with gemcitabine in patients with high levels of tumor associated hyaluronan (HA). These results are being presented at European Cancer Congress 2013 (ECCO-ESMO-ESTRO) in a poster session at 14:00 CEST (Hall 4, Abstract #2598). Early response rates from this trial were previously presented at the 2013 American Society of Clinical Oncology (ASCO) Annual meeting in June 2013.
The accumulation of HA, a protective matrix that surrounds many solid tumors, has been shown to be an indicator of poor patient prognosis and may accelerate disease progression. In this single arm study, all patients received PEGPH20 in combination with gemcitabine. The primary objective was to determine the recommended phase 2 dose. Exploratory analysis evaluated PFS and OS in a subset of patients with available biopsy samples and HA scores. In patients with high levels of tumor HA (n=6), PFS was 219 days compared to 108 days for patients with low levels of tumor HA (n=11), while OS in the high HA group was 529 days compared to 174 days for the low HA group. OS data is still not mature for the high HA group. With respect to the intent to treat population irrespective of HA status (n=24), PFS was 154 days and OS was 200 days.
"PEGPH20 has been shown in animal studies to deplete HA from tumors and improve perfusion and drug delivery to the tumor bed. The data from this trial suggest that similar processes may be occurring in patients as well and that patients with high levels of HA may derive the most treatment benefit from PEGPH20 combination therapy," stated Sunil R. Hingorani, M.D., Ph.D., Associate Member of the Clinical Research and Public Health Divisions at Fred Hutchinson Cancer Research Center and lead investigator for this study. "Pancreatic cancer is a devastating disease, and these data provide intriguing evidence for a new treatment paradigm. We look forward to the results for PEGPH20 in large randomized Phase 2 trials with the most active chemotherapy regimens available to definitively establish the potential benefit of this strategy and correlation with HA status."
Additional Study Details
This study enrolled 28 patients with stage IV treatment naïve pancreatic ductal adenocarcinoma. Patients were treated with one of three doses of PEGPH20 (1.0, 1.6 and 3.0 µg/kg twice weekly for four weeks, then weekly thereafter) in combination with gemcitabine 1000 mg/m2 administered intravenously. The overall response rate (ORR) (complete response + partial response) by RECIST 1.1 criteria was 42 percent (10 of 24 patients, 95 percent CI 22 – 62 percent) in the intent to treat population for those treated at therapeutic dose levels of PEGPH20 (1.6 and 3.0 µg/kg). Additionally, 43 percent of evaluable patients saw a reduction of at least 70 percent in serum carbohydrate antigen 19-9 (CA 19-9), a biomarker of tumor cell burden.1 In the intent to treat population, 17 patients had biopsies evaluable for HA scoring. The method of HA scoring was prospectively defined for tumor-cell associated and stromal associated tissue, and assessed by central pathology laboratory evaluation. The ORR in patients with tumor-cell associated high HA was 83 percent, indicating that tumor-cell associated HA may be a better predictor of PEGPH20 combination treatment effect compared to stromal associated HA.
Treatment was generally well tolerated, and the adverse event profile was consistent with those seen in previous studies of PEGPH20 as a single agent and as previously reported for gemcitabine alone. The most common adverse events for PEGPH20 were muscle spasms, myalgia and arthralgia (all grade 1/2). There was no evidence of new toxicities when used in combination with gemcitabine and the pharmacokinetics of PEGPH20 with gemcitabine was consistent with the pharmacokinetics of PEGPH20 as a single agent. Additionally, the pharmacodynamic and pharmacokinetics results support the dosing regimen of PEGPH20 at 3µg/kg, which is being used in an on-going Phase 2 trial.
Halozyme has initiated a Phase 2 multicenter, randomized clinical trial evaluating PEGPH20 in combination with nab-paclitaxel and gemcitabine to confirm the combination treatment effect (ORR, PFS and OS) based on HA levels. The study plans to enroll approximately 124 patients with stage IV pancreatic ductal adenocarcinoma. Halozyme is also developing an HA diagnostic tool to be used in this study to evaluate the potential treatment benefit based on tumor HA levels at baseline. This diagnostic approach may enable additional PEGPH20 combination clinical studies in other HA-rich tumor types.
Emerging data show that most pancreatic cancers surround themselves with a protective hyaluronan-rich matrix, which makes the disease difficult to treat and is itself an indicator of poor prognosis. PEGPH20 has been shown to deplete this matrix component from the tumor and rapidly changes the tumor microenvironment and metabolism, which may render the tumor more vulnerable to therapy as well as inhibit tumor growth.
About Pancreatic Cancer
In most patients diagnosed with metastatic pancreatic adenocarcinoma, survival rates are the lowest of any cancer. In 2013, it is estimated that almost 45,000 new cases of pancreatic cancer will be diagnosed. About one-in-78 people in the U.S. will develop the disease, affecting equal numbers of men and women, almost always after the age of 45. Its tendency to spread prior to diagnosis makes it the fourth deadliest cancer with a less than six percent five-year relative survival rate, with more than 38,000 people succumbing to the disease each year.2-3
Halozyme Therapeutics is a biopharmaceutical company dedicated to developing and commercializing innovative products that advance patient care. With a diversified portfolio of enzymes that target the extracellular matrix, the Company's research focuses primarily on a family of human enzymes, known as hyaluronidases, which increase the absorption and dispersion of biologics, drugs and fluids. Halozyme's pipeline addresses therapeutic areas, including diabetes, oncology and dermatology that have significant unmet medical need. The Company markets Hylenex® recombinant (hyaluronidase human injection) and has partnerships with Roche, Pfizer, Baxter, and Intrexon. Halozyme is headquartered in San Diego, CA. For more information on how we are innovating, please visit our corporate website at www.halozyme.com.
Safe Harbor Statement
In addition to historical information, the statements set forth above include forward-looking statements including, without limitation, statements concerning the possible activity, benefits and attributes of PEGPH20, the possible method of action of PEGPH20 and its application in a new potential paradigm for treatment of pancreatic cancer, future clinical trials for PEGPH20, the development of the HA diagnostic tool and its potential uses, and the possible utility of PEGPH20 in pancreatic cancer and other tumors. The forward-looking statements are usually (but not always) identified through use of the words "believe," "enable," "may," "will," "could," "intends," "estimate," "anticipate," "plan," "predict," "probable," "potential," "possible," "should," "continue," and other words of similar meaning. Actual results could differ materially from the expectations contained in forward-looking statements as a result of risks and uncertainties including clinical trial enrollment and results, regulatory approval requirements, unexpected expenditures and costs, unexpected results or delays in development and regulatory review, unexpected adverse events and competitive conditions. These and other factors that may result in differences are discussed in greater detail in the Company's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on August 7, 2013. Halozyme does not undertake to update these forward-looking statements.
References 1. Pancreatic Cancer Treatment, National Cancer Institute, http://www.cancer.gov/cancertopics/pdq/treatment/pancreatic/HealthProfessional/page1/AllPages.Accessed September 19, 2013 2. American Cancer Society, Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013. 3. Pancreatic Cancer, American Cancer Society,http://www.cancer.org/cancer/pancreaticcancer/detailedguide/pancreatic-cancer-key-statistics. Accessed September 19, 2013.
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