Individualised approaches to medicine

Rebecca Aris interviews Mark Frohlich

Dendreon

Tp begin our personalised medicine focus month, we speak with Mark Frohlich of Dendreon around the difference between personalised medicine and individual therapies and the potential of immunotherapies.

Personalised medicine has attracted much media attention of late. Immunotherapy harnesses a patient’s own immune system to fight their cancer and is therefore individualized. However, it differs from other personalised medicines. Confusion exists around the terminology, which can often lead to public misunderstanding.

Dendreon develops cancer immunotherapies. We interviewed Mark Frohlich of Dendreon on Dendreon’s current focus, how its products deliver personalised medicine and the potential of immunotherapies.

Interview summary

RA: Mark, thank you for joining me. How do you define personalised medicine?

MF: I would define it as individualising the treatment of a patient to their particular body and /or cancer.

RA: You’re viewed as a company involved in personalised medicine, and yet you don’t consider immunotherapy to be a personalised medicine. Where does this confusion lie?

MF: I would consider our immunotherapy to be a personalised medicine. However, the term ‘personalised medicine’ is most commonly used to refer to the sampling of a patient’s particular tumour, and the tailoring of the patient’s treatment based on a molecular analysis of the tumour’s profile.

Our immunotherapy is personalised in that we activate the patient’s own immune system to target their cancer. In the case of our approved immunotherapy for advanced prostate cancer, Provenge, we target the immune system to a tumor antigen, which is known to be expressed in almost all prostate cancers, so we don’t need to profile each patient’s individual tumor. Both approaches are individualised, but in different ways.

RA: What are the key challenges and opportunities associated with immunotherapy?

MF: One of the challenges is that the way the therapy works is different from traditional therapies. Immunotherapies stimulate the immune system in the body, which then targets the cancer. It therefore takes time for that immune system to build and to be able to fight the cancer.

In contrast to traditional therapies like chemotherapy, you may not see the tumour shrinking or tumour markers going down, or effects on short term markers like disease progression.

Our immunotherapy, Provenge, has been demonstrated to prolong overall survival. Because it is the first and only approved active immunotherapy for cancer, physicians and patients need a lot of education to help them understand that they can still be benefiting from the therapy, even if the tumour is not shrinking on an imaging scan or a tumour marker measured in the blood isn’t decreasing. We have shown that Provenge prolongs overall survival in randomised phase III trials, even without measurable effects on disease progression measures.

&nbsp,

“In contrast to traditional therapies like chemotherapy you may not see the tumour shrinking or tumour markers going down…”

&nbsp,

RA: How do we manage the challenges associated with the immunotherapy given the small patient volume and the need for commercial return?

MF: I don’t think that there’s necessarily a small patient volume. We’re targeting the metastatic castrate resistant prostate cancer, which in the US is a patient population of probably 60,000 or 80,000 patients. That presents a sizeable opportunity, both in terms of the number of patients who can benefit as well as commercially.

Part of the challenge is that the cost of making these therapies is much higher than it is for small molecules or antibodies, which can range from pennies to maybe hundreds of dollars for a dose. An individualised immunotherapy requires a much greater investment for each individual patient. In the case of Provenge, we harvest blood three times from the patient. Each time we ship it to a central manufacturing facility, incubate it for approximately 2 days to activate the cells, and then ship the product back to the physician’s office to be infused.

It’s obviously much more resource intensive, but these are logistical challenges that can be overcome. Since the commercial launch of Provenge, Dendron has become much more efficient in its supply chain and manufacturing processes.

As we see increased volumes of patients, we will be able to further optimise our processes and are currently working towards automation of the manufacturing process.

RA: How do you think we can better communicate what personalised medicine and immunotherapy is to healthcare providers and patients?

MF: I think that’s going to be a gradual educational process. The success of other immunotherapies, such as ipilimumab for metastatic melanoma, has helped people to appreciate that this is a growing trend, which is really going to revolutionise the treatment of cancer. Immunotherapy has the benefits of being very effective, prolonging overall survival. In the case of Provenge, the therapy is of very short duration, administered in approximately 1 month, and has a very favourable safety profile.

You don’t have the toxicities associated with chemotherapy that may require growth factor support, hair loss or other side effects, and sometimes hospitalisations. Those things can reduce a patient’s quality of life and also contribute to the cost of care too. These are factors that are often not fully appreciated when people compare an innovative, personalised immunotherapy approach with traditional approaches such as chemotherapy.

&nbsp,

“The tools to identify antigens exist and in the future those diagnostic tests will be developed in parallel with immunotherapy.”

 

RA: How aligned is the diagnostic market with current progress in immunotherapy?

MF: The diagnostic market is presently more geared towards the typing of patient tumours to determine what the particular aberrations are that may be driving the tumour.

In our case, we chose a tumour antigen for the immune system that is present in virtually all patients with prostate cancer. Initially, in our early trials, we were testing all the patients for expression of that protein. When we found that virtually all patients expressed the protein, we decided that it wasn’t necessary to test for its presence, and the FDA did not require us validate a diagnostic test.

This won’t necessarily be the case for other cancers. For example, we currently have a trial ongoing now in bladder cancer, in which we are targeting the tumour antigen HER2. Because it is expressed in about half the bladder cancer patients, we do need to test for it. In this case, there already is a HER2 test, because it’s used for identifying patients who are appropriate for the antibody therapy Herceptin in breast cancer, but we may need to do some additional validation work in bladder cancer.

The tools to identify antigens exist and in the future those diagnostic tests will be developed in parallel with immunotherapy.

The way that the field is heading is to target multiple tumour antigens. If you target enough of those, such that virtually all patients in a particular disease type express one or more of those, it may not be necessary to have a diagnostic test associated with it.

RA: What is next for Dendreon?

MF: Our first priority is to ensure that as many patients as possible who are within the current FDA label indication and have the potential to benefit from Provenge, receive it.

We’re also pursuing a licence application in Europe, and we’re interested in applying this platform to patients with other cancers. As I mentioned, we currently have a bladder cancer trial ongoing. We’ll also be looking at a variety of other cancers that we can target with this approach.

There is a tremendous opportunity to combine our immunotherapy with other types of biologic agents. We have investigator initiated trials going on as well as company-sponsored trials looking at combinations of Provenge with either standard agents or biologic agents.

There is a real biologic possibility for synergy between agents like that. If that’s something we can demonstrate, it could dramatically improve the outcome of patients.

RA: Mark thank you very much for your time today and for your insights.

&nbsp,

press-releases-pharmaphorum

 

About the interviewee:

Dr. Frohlich serves as Dendreon’s executive vice president of research and development and chief medical officer. Prior to joining Dendreon, Dr. Frohlich was vice president and medical director at Xcyte Therapies, a biotechnology company. Prior to that was an assistant professor in the Division of Hematology / Oncology at the University of California, San Francisco, where he specialized in urologic oncology and was active in laboratory, translational and clinical research. Dr. Frohlich did his post doctoral training in oncology at the University of California, San Francisco. He received his B.S. from Yale University in electrical engineering and economics and his M.D. from Harvard Medical School.

What are the key challenges and opportunities associated with immunotherapy?