We hear the word chemotherapy all the time. It’s a treatment associated with most cancers. But its ubiquity also masks a hidden secret: The chemotherapy field for brain cancer specifically is woefully out of date. The reason for this has to do with the blood/brain barrier and the need for a medicine that can cross it. Not all chemotherapies can do this, which is what makes the available supply of chemotherapy drugs for brain cancer very limited.
There are technically five chemotherapy drugs available to treat brain cancer, but one of them heavily outsells the others. Temodar from Merck & Co., Inc. (NYSE:MRK) sold $882M in 2012 before its patent expiry. The other four have been generic for a long time, including Lumustine, rebranded as Gleostine in 2014 from Nextsource Biotechnology, a private firm. Matulane has been around since 1969. Oncovin was once an Eli Lilly & Co (NYSE:LLY) bestseller but is now only a minor player with some new reformulations of the drug in development. The Gliadel wafer is the fifth, a chemotherapy manually inserted into a surgical site post resection, but sales are minimal. That leaves Temodar nearly all alone at the top.
Even worse for brain cancer patients, Temodar is not all that effective on nearly two thirds of patients with the most lethal form of the disease. Glioblastoma multiforme is one of the most aggressive cancers known, and is sadly the most common form of brain cancer. The reason for Temodar’s ineffectiveness on two thirds of patients is an enzyme called MGMT that defends the tumor against Temodar’s attack in this patient population.
This sordid state of affairs for GBM sufferers may change relatively soon. A new chemotherapy called VAL-083 by DelMar Pharmaceuticals Inc. (NASDAQ:DMPI) just entered Phase II development. VAL-083 is known to bypass MGMT protection of the tumor. While new in the sense that it is now being developed commercially, it has actually been known about since the 1970’s. Earlier trials on VAL-083 conducted by the National Cancer Institute (see table below) have shown that VAL-083 looks to be superior to Temodar in terms of median and overall survival.
Keep in mind though that these earlier trials did not differentiate between high MGMT and low MGMT expression patients. DelMar’s new Phase II trial is only enrolling high MGMT expression patients, which means that if DelMar is right about VAL-083’s mechanism of action, improved results over Temodar (TMZ above) should be even more pronounced. The trial will enroll 48 patients, and from there the company is looking to begin a pivotal Phase III on 180 patients that will serve as a basis for approval.
The trial is actually DelMar’s first step in the clinic for VAL-083, the previous steps already having been completed by the NCI. Since the patient population for GBM cancer is so small and the trial is on refractory cancer, meaning cancer that has already failed standard-of-care treatments like Temodar, no placebo arm will be necessary and open label results will be known from interim reports, giving shareholders and patients and their families an earlier indication of the potential of this new/old drug before the trial is completed.
Shares of DelMar have already responded very well to the announcement of the new trial with shares up 41% since news went public. For a lesser-known company like DelMar, the response indicates market readiness for a new approach to GBM brain cancer. Marketing should not be an issue here as the patient population is so focused.
The path to approval from here is, first, to complete this Phase II of 48 patients, and then move on to a pivotal Phase III of 180, estimated by DelMar to take about 20 months to complete once it starts. Extrapolating from those numbers, this 48-patient trial could take as little as half a year at the same rate. However long it does take in reality, we should be getting interim results as they become available throughout 2017.
Meaning, this year should give us a pretty good clinical indication of whether VAL-083 is a viable replacement for the $882 million near-blockbuster Temodar.