Cancer Immunotherapy: Is the Hype Over and the Hope Beginning?

The simplistic and lazy cancer vaccines are immunotherapy: treatments that stimulate a patient's immune system to fight cancer.

A decade or more ago, in a capital market far far away, cancer immunotherapies and treatments, and the companies that researched them were white hot. Due to the incredible time it takes to develop these therapies and the lack of clear regulatory guidance and pathways at the FDA, they have been stuck in trials -- and, understandably, investors have run for cover.

But now, they may be on the rebound -- for patients and for investors.

What is cancer immunotherapy?

I prefer a very narrow definition when talking about investments: new drugs designed to turn on the patient's immune system to fight cancer on it's own.

Wikipedia has a good working definition that also includes some broader approaches beyond my own definition.

When I talk about cancer immunotherapy (and when Wall Street talks about immunotherapy companies) it is the treatment, stimulation and management of a patient's own immune system to fight cancer in many forms. Treatments are being developed to either prevent the onset of cancer, almost like a traditional vaccine or immunization, or to stimulate a patient's immune system after the onset of the disease typically by injecting therapeutic antibodies.

Different kinds of cancer tumors have cells that have unusual type of antigens (go to Wikipedia for this one also) and these are often the targets of immunotherapies -- especially antigens that appear on the surface of cancer cells and are relatively easy to get to.

Research scientists also look for something called "cell surface receptors." These do not occur with any frequency in a healthy patient and are an integral part of the duplication process of cancer cells, and if an immune system can stop these receptors, a tumor, theoretically, could stop growing.

Who plays in this arena? The most infamous company is Dendreon (DNDN) and its prostate cancer treatment Provenge. The success (at a panel) and failure (with the FDA staff) of this drug in the approval process highlights the problems facing developers of these treatments. The problems:

• What to treat? When these companies got started, "tumor shrinkage" or the stopping of tumor growth was all the rage. Now, they are being asked to extend life, a much more logical target but this changes things. Dendreon's trials of Provenge failed to stop tumor progress but one small one seemed to show a survival benefit.

• Who is the regulator? Most cancer drugs are regulated by a group at the FDA known to some of us -- the wittier ones -- as statistical fascists. The panels convened by this group to review new treatments are dominated by practicing oncologists who see two weeks more survival as a relevant fact. It is not.

  Some of the immunotherapy companies are regulated by a different group at FDA and they are far more sensitive to the issues facing brand new technology. This group stacked the panel looking at Provenge with seven immunologists -- and lost the battle with the statistical fascists within the agency, and the drug was rejected. It was the first cancer treatment approved by a panel and rejected by staff in living memory. This mess -- and it is a mess! -- makes handicapping the potential success of a treatment in trial and the approval process very difficult.

• How to measure progress? If life extension is what counts, trials need to be much longer than a trial to measure tumor progress -- the new trial for Provenge is three years long -- and trials need to be managed very well with most patients at the same stage of the disease when entering the trial.

  Most start up biotechs lack the management ability to keep their bathroom stocked with toilet paper and are very poor at managing trials the way the FDA wants them managed. The executive teams at these companies are also populated with arrogant scientists not willing to listen or work with public servants. I kid you not. So many trials are still underway that are aiming at something other than life extension.

• Manufacturing: Many of these treatments require processing of an individual's patient's blood -- some involving the taking of tumor tissue samples -- and this requires a manufacturing facility that requires FDA approval and a whole new FDA set of regulations. A great book is "Inside the FDA" by Fran Hawthorne, which will give you a good look at how tortured this process can be.

• Does it work? Traditional high profile oncologists -- used to poisoning and burning patients or giving them cocktails of drugs they put together outside FDA labels -- want more data.

  I don't. Provenge clearly works on some sub-group of advanced prostate cancer patients, and these people are going to die anyway. Other treatments have failed, notably a treatment from Antigenics (AGEN). Let us hope the arrogant doctors who manage these companies and the arrogant doctors on the FDA panels abandon Francis Bacon, at his worst, and let one through. And then another, and another....
  

Dendreon (DNDN): Avoid this dog. Management is screwing up the trial process again and the new trial will be interrupted to present interim results to get an expedited FDA approval at the end of 2008. The betting money is the trial will fail to show life extension because they enrolled the easier-to-find patients in the trial first - the sickest patients. A dumb move.

Cell Genesys (CEGE): They are also working in an advanced prostate cancer treatment, GVAX, and their trials are constructed to show life extension and also in conjunction with other known treatments, so if the therapy works, they may have a fighting chance to get an approval.

Antigenics (AGEN): Probably a dead company, their drug did not work, they have burned through oodles of investor cash, stay away.

Oxford Biomedica PLC (OXB: LSE, London Stock Exchange): They just concluded a huge deal with the Sanofi-aventis (SNY), potentially worth more than half a billion dollars, as SNY tries to play catch up in the $50-billion-dollar-per-annum cancer treatment market.

Big pharma: The dinosaurs working in this area are Sanofi-aventis, GlaxoSmthKline (GSK) and German company Merck Kga. Stay away, dinosaurs are just that, dinosaurs.

Bottom line: If investors continue to support these companies -- and just one drug works and gets an approval -- all hell will break loose to the upside for there is a great need for a next-generation approach to cancer treatment.