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One of the difficulties that investors face in emerging healthcare biotech is rooted in understanding what they are paying to develop. Of course there will be a small number who do, but in the majority of cases the nature of the industry means that investors are relying solely on simplified explanations of complex processes to form judgment. There is also a sales bias involved. Like it or not, if two companies are developing the same treatment and one of them shouts louder about it, they will inevitably draw more investment.

Couple these two factors with the hit and miss nature of the FDA's approval process, and you will have an extremely risky sector. There is one way to reduce a substantial portion of this risk however, and it is rooted in the science. Improve your understanding of what is being developed; how it improves upon the current standard of care; and what its chances of FDA approval are, and you can vastly increase your chances of backing the right company. This article will focus on these three areas, in a "hot-topic" area of cancer treatment - dendritic cell immunotherapy. The treatment I will be considering is DCVax-L; the company that develops it, Northwest Biotherapeutics (NWBO).

What is DCVax-L?

A simplified explanation of how the treatment works can be found on NWBO's website. It states:

"DCVax®-L is an experimental autologous cellular therapy designed to create a specific immune response against a patient's cancer."


"DCVax®-L utilizes a patient's own dendritic cells (DC), and an extract of the patient's own tumor cells to achieve an immune response."

But what does this mean? First, let's consider the cancer. DCVax-L is designed to treat a very specific form of brain cancer called Glioblastoma Multiforme [GBM]. 60% of brain tumors are diagnosed as astrocytoma, which simply means that they start in the brain or spinal cord, and GBM is the most deadly of all diagnosed astrocytoma. The median survival rate without treatment is a little over 4 months, and with current standard of care treatment survival is 15 months.

Now, a look at the treatment. There are two main forms of cell therapy, autologous and allogeneic. Autologous refers to treatment using cells from the patient's own body, and allogeneic refers to using cells from someone else. DCVax-L is autologous. The human immune system works in two ways. The first of these, the innate immune system, is our "first line of defense". It kicks in when we get sick. The second is the adaptive immune system, which is the part of the system that develops long term defense against pathogens. It serves to "remember" certain pathogens, and create an immune response if we encounter them. DCVax-L takes advantage of the adaptive side. Dendritic cells play a major role in this adaptive system. They are what is referred to as "antigen presenting", which means they present the T-Cells with an antigen that is on the cell that is to be attacked, and the T-Cells then attack any other cell in the body that has the same antigen.

This is how dendritic cells are used in DCVax-L. After the tumor is removed from the brain and combined with white blood cells from a blood sample. These white blood cells are then allowed to "mature" into dendritic cells. The dendritic cells now have the tumor antigen, and when they are reintroduced into the body the T-Cells read this antigen, and can recognize the tumor as something to attack.

DCVax-L is not designed to attack the entire tumor and destroy it. Rather, it is designed to equip the immune system with the cells necessary to prevent its recurrence. One of the biggest problems with GBM is that it often recurs because it is extremely difficult to remove every cell of the tumor from the brain during surgery. However, if the immune system can recognize the tumor, it can attack the remnants of it after it is removed and drastically reduce, or even eliminate recurrence. This is the goal of DCVax-L, and therefore it only applies to those whose tumors are operable.

How does it compare to the current standard of care for GBM?

The current standard of care treatment for GBM is a combination of surgery, radiotherapy and chemotherapy. None of these treatments are particularly effective on GBM however, for a number of reasons.

Let's look at surgery. Surgery on the brain is extremely risky, for obvious reasons. Also, GBM cells are extremely infiltrative. Even if 99% of the tumor is removed (not uncommon) the GBM cells are so widely spread that secondary tumors are likely to develop.

Next, radiotherapy. Once the primary tumor is all but removed, most patients undergo radiotherapy. Those patients that do are reported to have a life expectancy double that of those who don't, but having one's brain radiated it is not without its problems. Other than side effects, one major problem is rooted in GBM cell hypoxia, meaning that the cancer cells are oxygen starved. Hypoxia is very common in GBM cells because they grow so fast that the body cannot supply them with enough oxygen. Oxygen-starved cells happen to be much more resistant to radiation, to the point where it can render radiotherapy ineffective. Brain radiotherapy itself is also extremely unpleasant and comes with serious quality of life issues. To say the least, it will cause hair loss at the site where the radiotherapy beams pass in and out of the brain and can cause extreme fatigue, nausea, and untold more side effects.

Finally, chemotherapy. The chemotherapy drug most commonly used in the treatment of GBM is called Temozolomide, which acts to disrupt cell growth. A study suggests that treatment with a combination of radiotherapy and Temozolomide can increase the median overall survival to 12 months, versus 8 months with just radiotherapy. Of course, there are many negative side effects associated with chemotherapy. The way chemotherapy works is by attacking cells with high rates of reproduction. Most adult cells don't reproduce that quickly. Some do however; hair, nails and the lining of the digestive system for example. As a result these are attacked by the chemotherapy drugs and induce the negative side effects that have become most commonly associated with cancer treatment.

The benefit of DCVax-L when compared with these three current standard of care treatments is rooted in its targeted approach. Because the dendritic cells carry only the GMB tumor antigen, the T-Cells it instructs to attack will only attack the tumor. No collateral cell damage is experienced, so no hair loss, digestive difficulty, tiredness, nausea etc.

What are its chances of success?

While the outcome of clinical trials are notoriously difficult to predict, some indication as to DCVax-L's chances can be gleaned from a consideration of the current phase endpoints and the previous phase data. DCVax-L is currently in the final phase 3.

The primary endpoint for the trial is an increase in progression free survival, or PFS. PFS simply refers to the length of time during and after treatment during which the disease does not get worse. The PFS associated with standard of care treatment for GBM is just short of 7 months. For patients who underwent DCVax-L treatment the PFS was a median 25 months, a 350% increase.

The secondary endpoint for the trial is an increase in overall survival, or OS. OS is the length of time from the start of treatment that half of the patients in the trial are still alive. The OS associated with standard of care treatment for GBM is 14 months. For patients who underwent DCVax-L treatment the OS was just over 36 months, a 250% increase.

These phase 1/2 results are derived from a much smaller dataset, and as such cannot be relied upon to guarantee reproduction, but such a dramatic increase in both the primary and secondary endpoint figures indicates that DCVax-L does at least stand a chance.

A little about NWBO

NWBO is an American company. The company's main focus is the development of immunotherapy treatments for various types of cancer, using its DCVax system. It is currently trialing DCVax-L in the US and Europe, but DCVax-L is not the only treatment that NWBO has in its pipeline. The DCVax process can be applied to a number of other cancers. One such application is DCVax-Prostate, which is in now frozen in phase 3 prior to enrollment pending the outcome of DCVax-L. The treatment works in much the same way as DCVax-L, but a specific antigen present in all prostate cancers called Prostate Specific Membrane Antigen [PSMA] is combined with the dendritic cell in place of the brain tumor tissue used in DCVax-L. The treatment is also in phase 3 clinical trials and, if successful, will expose NWBO to a global market estimated to be worth over $50B by 2017.

Also in the pipeline is DCVax-Direct. Another dendritic cell cancer vaccine therapy, aimed at all inoperable solid tumors. NWBO announced the commencement of an open label combined phase 1/2 clinical trial for DCVax-Direct in June this year, with data coming out on a patient by patient basis, the first of which should be coming out by the end of this year. Although not particularly indicative of human efficacy, DCVax-Direct worked to completely eradicate tumors in some mice, and is therefore an exciting prospect for the future.


The aim of this article was to look at the science behind NWBO's lead cancer treatment, and use this to determine its advantage over the current standard of care and its likelihood of success in its ongoing clinical trials. The treatment is supported by sound scientific principles, and data so far shows that it has a number of benefits over the currently available treatments in both overall effectiveness and improving patient quality of life. Results are expected early 2014, and if approval is achieved, in time DCVax-L could become the new standard of care treatment for GBM sufferers.

Source: A Closer Scientific Look At Northwest Biotherapeutics' Lead Candidate