Here’s What ’60 Minutes’ Didn’t Tell You About The ‘Miracle’ Glioblastoma Treatment
by Arlene Weintraub
Last night, CBS CBS -2.00%’ hit newsmagazine 60 Minutes devoted not one but two segments to an early-stage trial at Duke University of a cancer therapy that some patients are calling a “miracle.” It’s a genetically modified form of the polio virus, injected directly into the brains of patients with glioblastoma, a particularly deadly type of brain tumor. Eleven of the 22 patients treated so far died, but the other 11 have seen their tumors shrink. Three featured in the story are cancer-free.
No wonder correspondent Scott Pelley and more than a few doctors and patients were throwing around the word “cure” during the piece. This is usually a devastating diagnosis: Median survival is little more than 14 months and two-year survival is just 30%, according to the American Brain Tumor Association. The disease takes 12,000 lives per year in the U.S. Surely anything that makes a glioblastoma melt away is worth some attention.
The virus was engineered by Dr. Matthias Gromeier, a molecular biologist at Duke who has been working on the treatment for the last 25 years. As Pelley explained, Gromeier removed part of the virus’ genetic material, which rendered it incapable of harming normal cells. That means it can only replicate in cancer cells, and in the process of doing so, it kills them while sparing healthy tissues. It’s a promising new approach in the burgeoning area of cancer immunotherapy.
But this is just a Phase I study, and as has been shown so many times in the past with experimental cancer treatments, early hopes are so often dashed. Here are some caveats to keep in mind as this therapy makes its way through the development process.
Polio is far from the only virus being studied as a cancer treatment.
The idea of using viruses as weapons against cancer isn’t new. It actually dates back to the late 1800s, when physicians treating cancer patients started reporting miraculous remissions in patients who came down with the flu or some other virus. By the 1950s, scientists understood that some viruses have a unique ability to invade just about any cell in the body and kill it. But turning that ability into cancer treatments was challenging: Either the virus-based drugs were too weak to wage effective attacks against tumors, or they were so powerful they prompted dangerous immune responses in patients. (That actually happened to one of the patients in the Duke trial, as 60 Minutes reported.)
The advent of genetic engineering created a renaissance of sorts in the search for so-called “oncolytic viruses”—bugs that can be genetically altered so they only infect and kill cancer cells. The 60 Minutes segment played up the idea of using polio, the feared virus that world health organizations went to great lengths to eradicate, but scientists have also studied herpes simplex virus, vaccinia (cowpox, closely related to smallpox), and respiratory viruses. The aggressiveness of the bug is not what’s important here, but rather how amenable it is to the genetic engineering required to make it useful as a cancer drug.
There are more than a half-dozen companies with genetically engineered viruses making their way through the development path, including biotech giant Amgen AMGN -0.63% It made waves in 2011 when it shelled out $425 million plus $575 million in milestone commitments to buy Biovex, which invented a herpes-based treatment for melanoma.
Several smaller companies are also working in this field, including Oncolytics Biotech ONCY +% DNATrix, and Oncos Therapeutics. But these companies have faced plenty of research disappointments and development challenges. Jennerex Biotherapeutics, which was working on a viral therapy for liver cancer, for example, flunked a Phase II trial and was bought out by a South Korean company in late 2013. The drug didn’t hit the trial’s endpoint for overall survival.
Amgen’s treatment is up for FDA approval, but it’s no slam-dunk.
Amgen’s treatment derived from the herpes virus, talimogene laherparepvec (T-VEC), is currently awaiting FDA approval, and the agency has scheduled an advisory committee meeting to discuss the drug on April 29.
As promising as this drug is, no one is using the word “cure” to describe it. In one trial, 16% of patients who got the experimental treatment saw their tumors shrink for at least six months, compared to 2% of patients in the control group. A later Phase III trial produced a “durable response” but missed the endpoint for overall survival.
The FDA doesn’t have to follow the advice of its advisory committees but it usually does, so the outcome of the meeting on Amgen’s drug will be closely watched by everyone working to bring virus-based cancer drugs to market.
What’s the business model here? Hard to say.
Some virus-based cancer treatments, including Amgen’s, are administered to patients on an ongoing basis. But others—the Duke treatment, for example—are designed to work with just one dose. The modified polio virus continues to work years after infusion, eating away at the tumor until it’s gone, according to the scientists featured in the 60 Minutes piece.
How can a company make money on a one-time treatment? That’s an open question, though it’s certainly not the first time it’s been asked in oncology. The University of Pennsylvania is working on a treatment that involves removing the white blood cells from cancer patients, using a modified HIV virus to re-engineer them, then infusing them back into the body, where they proceed to attack cancer cells. Novartis is backing the project and expects to file for FDA approval by 2016.
The invention of these modified cells, known as chimeric antigen receptor T-cells, or CARTs, has turned into one of the hottest pursuits in oncology research, with Novartis now competing against Juno Therapeutics and several startups. It’s not yet clear, however, how any of them will scale-up the production of the personalized therapy in a way that will prove profitable.
Caveats aside, the precedent set by Novartis’ support of Penn’s project certainly bodes well for Gromeier and the rest of the Duke team. The researchers, who are supported by grant money and philanthropic donations, are planning a Phase II/III trial in glioblastoma, and they are interested in exploring the therapy in other tumor types, including pancreas, prostate, and lung cancer.
They expect to hear in about year if the modified polio virus will be awarded “breakthrough” status by the FDA. That designation would greatly speed up the development process—and likely draw the interest of the deep-pocketed investors needed to take on both the promise and risk of this experimental therapy.
FOR INFOTMATION ON THE DUKE UNIVERSITY TRIALS SEE: