Reimagining a conventional way of attacking cancer is Rafael Pharmaceuticals’ idea of aiding a more immediate way of treating patients with pancreatic cancer, which is one of the most leading causes of death from cancer in the world.
Israeli researchers from Rafael Pharmaceuticals launched a phase III clinical trial on Thursday for pancreatic cancer at eight sites throughout Israel, which the company sees as a breakthrough for the drug that they are developing.
Rafael Pharmaceuticals is a leader in the growing field of cancer metabolism-based therapeutics. Supplementarily, their approach to helping expedite the process of extinguishing pancreatic cancer from patients is to starve the cancer cells to death with the help of other existing medical solutions.
Meanwhile, the concept of starving cancer cells has been a long tried approach to attack the problem from the root—starve them enough to prevent them from dividing and cause eventual cell death. However, previous attempts have continuously failed to show much promise that proves it to become an effective track to follow.
As an effort, Rafael Pharmaceuticals is looking at a drug called CPI-613, which activates two key tricarboxylic acids (TCA) cycle enzymes called Pyruvate dehydrogenase and alpha-Ketoglutaric dehydrogenase. Particularly, these TCA cycle enzymes are responsible for signaling cells to release stored energy.
Basically, CPI-613 mimics the processes of chemical reactions performed by the two mentioned above TCA cycle enzymes. But specific to the drug, it “feeds misinformation to these regulatory elements, making them feel that there is too much carbon flow” and signal cancer cells to release stored energy. Essentially, the cells eventually die or weakened as a result.
Tim Pardee, Rafael’s Chief Medical Officer, also noted that the drug also offers many benefits: “[CPI-613] simultaneously inhibits both complexes so tumor cells that are primarily driven by glucose cannot utilize glucose in the TCA cycle. Tumor cells that are primarily driven by glutamine usage cannot use glutamine-derived carbons in the TCA cycle. And, importantly, tumors cannot switch from one source to the other in the presence of CPI-613.”
In other words, one benefit with their drug is that cancer cells cannot utilize their primary source of energy, such as glucose, to grow and replicate because CPI-613 feeds them information that there is already an abundance of which. While the second benefit is that for the cells to develop resistance to the drug is unlikely, and the third, the drug is highly selective; thus, it will hardly cause significant damage to healthy cells.
Pardee adds that CPI-613 combined with other existing treatments such as chemotherapy can effectively expedite the process of curing pancreatic cancer, at least that is what their clinical trial is trying to prove.
As of the moment, the researchers are looking to perform phase III on a group that they are calling the AVENGER 500, where the first 250 people diagnosed with late-stage pancreatic cancer will be administered CPI-613 with a chemotherapy combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin, called FOLFIRINOX. Meanwhile, the next 250 will only receive chemotherapy treatment.
If the theory serves right, the pharmaceutical company will yield positive results by September 2020, and the company will be able to apply and receive expedited approval by the FDA. If not, he said that the earliest the drug would be on the market from this trial would be October 2021.
The trial kicked off at eight hospitals throughout the country, including Hillel Yaffe Medical Center, Yitzhak Shamir Medical Center, Soroka Medical Center, Sheba Medical Center, Rambam Health Care Campus, Laniado Hospital, Tel Aviv Sourasky Medical Center and Shaare Zedek Medical Center.
In particular with pancreatic cancer, it is the 12th most common cancer worldwide, with 458,918 new cases in 2018 alone. It is the fourth leading cause of cancer death and accounts for 7% of all cancer deaths, according to Cancer.Net.
Furthermore, the problematic thing about pancreatic cancer is that it is hard to detect early on, so researchers are hell-bent into finding solutions for the disease when it is already in its late stages, or it is already too late to administer early-on medical treatments.
Thus, the five-year survival rate for people with pancreatic cancer is 9%. For the 52% of people who are diagnosed after cancer has spread, the 5-year survival rate is 3%, Cancer.Net says.
“Every day, more than 1,200 people around the world receive a pancreatic cancer diagnosis, and our trial brings hope as the only Phase 3 clinical trial in metastatic pancreatic cancer,” said Sanjeev Luther, President and Chief Executive Officer of Rafael Pharmaceuticals. “The expansion of our trial into Israel is the first step in bringing our commitment to developing treatments for patients with significant unmet medical needs to a global level.”