April 6, 2017
By Alex Keown, BioSpace.com Breaking News Staff
SAN DIEGO – Halozyme Therapeutics’ experimental PEGPH20 is turning up the heat on cancer tumors as preclinical data is showing how the enzyme that targets and degrades hyaluronan (HA) is creating a hot environment for solid tumors, allowing immunotherapies to become more effective.
PEGPH20 is an investigational drug designed to bolster the efficacy of checkpoint inhibitors, Helen Torley, chief executive officer of Halozyme told BioSpace in an exclusive interview. Data released by the company earlier this month shows that PEGPH20 increases the effectiveness of a checkpoint inhibitor therapy and the number of cancer-fighting white blood cells accumulating in the tumor, particularly when HA is present. HA accumulates in higher concentrations around many solid tumors, potentially constricting blood vessels, impeding the immune response and the access of other therapies, Torley said.
“When the hyaluronan is present in the tumor, it’s a barrier to the checkpoint inhibitors,” she said in a telephone interview.
But, that changes when PEGPH20 is added into the mix, as the drug degrades the HA. During the American Association for Cancer Research (AACR) meeting Halozyme showed data models that PEGPH20 increased the anti-PD-L1 effectiveness by 411 percent compared to anti-PD-L1 alone as measured by tumor growth inhibition. Additionally, PEGPH20 increased the accumulation of CD8+ T cells by 176 percent (p=0.0025) in an HA-rich mouse model, the company said. Torley said she was pleased with the data and said that as far as she knows, Halozyme is the only company targeting hyaluronan.
PEGPH20 has the ability to bolster anti-PD-1 and PD-L1 therapies by making the tumor area “hot.” Torley said tumors are often described as having “gone cold,” which allows the cancer tumors to grow. PEGPH20 is able to turn the tumor “hot,” which allows the drugs to penetrate and attack the cancer cells, she said.
“This is such a hot, hot area of interest for companies,” Torley said.
She said the poster presentation of the data at AACR had people lined up six-deep to find out more about PEGPH20.
“Our data suggests we’re definitely having some impact,” Torley said.
It’s having such an impact that the U.S. Food and Drug Administration granted orphan drug designation to PEGPH20 for treatment of pancreatic cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic, pancreatic cancer. Torley said pancreatic cancer is an area the company is keen to see effective therapies developed. She said there are four approved therapies for pancreatic cancer, but they only provide incremental improvements in the typically fatal disease. Torley said these patients have some of the lowest survival rates and they are hoping that PEGPH20 can improve the rate of survival.
The company is developing multiple partnerships with large pharmaceutical companies such as Roche, Merck, Celgene, Pfizer, Janssen, AbbVie, and others.
Halozyme has an eight tumor collaboration with Roche, which includes pancreatic cancer, gastric cancer, cholangiocarcinoma and gall bladder cancer. Torley said these are some of the hardest cancers to treat with checkpoint inhibitors and the companies hope that the addition of PEGPH20 will improve those chances. PEGPH20 is being combined with Roche’s anti PD-1 drug, Tecentriq, which was approved by the FDA in October 2016 for the treatment of patients with metastatic non-small cell lung cancer.
PEGPH20 is also being used as an additive to a combination of Celgene’s Abraxane and gemcitabine in treating advanced pancreatic cancer.
Merck is running studies combining PEGPH20 with Keytruda, its anti-PD-1 immunotherapy drug in patients with advanced non-small cell lung and gastric cancers.
Additionally, the company is working with subcutaneous forms of PEGPH20 in combination with Roche’s Rituxan in multiple blood cancer indications. Halozyme also has a partnership with Janssen to study PEGPH20 with its multiple myeloma drug, darzalex. When it comes to the darzalex combination, Torley said PEGPH20 has dramatically lowered the amount of time it takes for darzalex to be administered intravenously, which frees up patients and caregivers to have more time to live their lives.
PEGPH20 has been a strong driver for Halozyme. The multiple partnerships the company has forged to test the efficacy of PEGPH20 allowed the company to expand its employment by about 30 percent in 2016, Torley said.
“We have our team in place now and we’re focused on executing our studies,” she said.
While the AACR data is certainly exciting, Halozyme has seen some disappointment. In March, Halozyme was notified by SWOG, a cancer research cooperative, that it suspended a Phase Ib/II trial evaluating PEGPH20 plus modified chemotherapy regimen Folfirinox versus modified Folfirinox alone in patients with previously untreated metastatic pancreas cancer had been temporarily closed to enrollment. The trial was suspended after the independent data monitoring committee determined preliminary data suggested the addition of PEGPH20 to the modified regimen of Folfirinox would be unlikely to demonstrate a statistically significant improvement in the primary endpoint of overall survival compared to the chemo drug alone. Torley said it was disappointing that PEGPH20 did not appear to benefit the chemo drug in that study.
Still, she said the number of studies PEGPH20 is included in will hopefully yield some positive outcomes. Torley said she anticipates readouts sometime in 2018 or 2019.
