From Forbes: A New Cancer Drug Worked In Over 25% Of Patients. What Does That Mean?

by Jon Fortenbury 9/10/2014 for Forbes: A new cancer drug, during a phase I trial, placed a patient with myelodysplastic syndrome in a complete remission that has lasted for more than three years. And it did so, in a non-invasive manner, setting forth a new way of treating cancer. CPI-613, a drug made by , benefited 29 percent of cancer patients during a phase I trial at Wake Forest Baptist Medical Center, enabling complete cancer removal in one patient, partial cancer removal in three and stabilization in two. Though the majority of patients involved in the study saw no change in their cancer situations, the drug caused minimal to no issues. The results of the study, which were published in the current online edition of the journal Clinical Cancer Research, have study leader Dr. Timothy Pardee envisioning the day where doctors can “leave the chemotherapy part out” for some patients. “That’d be a really exciting development that I think can be achieved in time,” said Pardee, director of leukemia translational research at Wake Forest Baptist Medical Center. CPI-613, which shuts down the production of energy in the mitochondria of cancer cells, is “directed toward exploiting the difference between normal and cancer cells,” said Cornerstone Pharmaceuticals president and COO Bob Rodriguez. Whereas normal cells use the energy in the mitochondria for essential functions, cancer cells use it to reproduce faster and repair damage from cancer treatments like chemotherapy. The 29 percent reported benefit of patients, it should be noted, was only for those who completed the trial, which started out with 26 patients with relapsed or resistant hematological malignancies (tumors of the blood, bone marrow or lymph nodes, such as leukemia and lymphoma) being given CPI-613 as a two-hour infusion. Five patients did not complete the trial: one refused, one obtained an infection and three developed acute kidney failure (which resolved in all but one patient). Once researchers determined the maximum tolerated dose, the drug didn’t produce any major issues. For the 21 who did complete the trial after that point (the median age was 65), they received CPI-613 on days one and four of each week for three weeks every 28 days. Ten went on to do more cycles of the drug than the trial asked for. Not everyone is sold on CPI-613, though. “I am concerned about the toxic effects seen in some patients and the generally low overall response rates seen in the cancer patients,” said Dr. Thomas Seyfried, biology professor at Boston College and author of Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer. Seyfried was not involved in the study, but thinks personalized metabolic therapies and drugs that are non-toxic to anyone, combined with the calorie-restricted ketogenic diet, is a superior way of treating cancer. CPI-613 doesn’t appear to be toxic at the right dosage, but it’s still too early to tell how it will affect a large number of people. According to Rodriguez, CPI-613 distinguishes itself from other cancer therapies by “leaving healthy normal cells unharmed under preclinical exposure conditions that kill a broad spectrum of cancer cells.” Also, no patients in the trial lost their hair or experienced reduction in bone marrow activity, which could leave them susceptible to potentially life threatening infections. With so many other cancer treatments harming or killing healthy normal cells, if CPI-613 does in fact leave them unharmed while treating cancer, it’d be ideal, but some, like Seyfried, remain skeptical of that being the case for everyone. It’s still being investigated why the drug was able to place in complete remission the man with myelodysplastic syndrome, which is a cancer where the bone marrow doesn’t produce enough healthy blood cells and instead produces abnormal cells in the blood and/or bone marrow. “At present, I can only guess that his cancer cells were wired in a way to be dependent on the mitochondria that we were able to inhibit,” Pardee said. CPI-613, Cornerstone’s primary drug, is in phases I, I/II and II of other clinical trials, being tested in patients with:

• Small cell lung cancer
• Advanced and/or metastatic solid tumors
• Relapsed or refractory myelodysplastic syndrome
• Locally advanced or metastatic pancreatic cancer
• Advanced cholangiocarcinoma (bile duct cancer)
• Metastatic pancreatic cancer (in combination with modified FOLFIRINOX)
• Relapsed or refractory acute myeloid leukemia (in combination with high doses of Cytarabine and Mitoxantrone)

The results of other trials have not been released or published yet. Cornerstone, a private New York/New Jersey-based company that has raised approximately $50 million from primarily individual investors since its incorporation in 2002, wants to give the researchers themselves the opportunity to release those results first. Cornerstone is not the only company exploiting the divergent metabolic process of cancer cells. There’s Agios, Calithera and a string of others. But the fact that CPI-613 was able to partially or completely remove the cancer in four patients gives Cornerstone, and potentially many cancer patients, a bright future.