Pharma Strategy Blog

A short while ago on this blog we began a series on Making a Difference about people in the cancer field who have a real passion and excitement for lasting and impactful change. The first one was an interview with Alain Moussy of AB Science in Paris.

Today, I had the pleasure of chatting with the admirable Dr. Susan Desmond-Hellmann, formerly Head of R&D at Genentech and now Chancellor at UCSF. It’s a strange business sometimes as we were both working in industry at the same time on different targeted cancer drugs in liquid and solid tumours but our paths never crossed, although it seems we share similar views on cancer drug development, ie purer targeted agents and finding faster ways to market for effective therapies that impact the lives of people with cancer.

Which brings me to the main topic of today’s discussion

There are many challenges in cancer drug development, not least of which are regulatory hurdles, time consuming, risky and expensive clinical trials (we’ve seen a lot of phase III failures lately), basic research, biomarker development and many others. Traditionally, cancer trials take two main strategies to market:

• Head to head comparison with standard care or a with and without approach if adding a new agent to the combination
• As a single agent in the relapsed, refractory setting

Both of these approaches are typically tested in the advanced or metastatic setting when the disease burden is relatively high and the risk of a drug failing in phase III trials is also high. In solid tumour cancers, once a drug has been shown to be effective, studies tend to move into the earlier, adjuvant setting after surgery has taken place but these trials can take a very long time to reach fruition, typically 5-10 years in some cases.

For many of us, the challenges of how to think outside the box and speed up development while treating earlier stage of disease more effectively has occupied many thoughts. Sometimes the bureaucracy across so many functions is just mind boggling.

No more.

Dr Desmond-Hellmann was telling me about the Investigation of Serial Studies to Predict your Therapeutic Response with Imaging and Molecular Analysis (I-SPY) project, which was launched in DC this morning and aims to change the way we think about cancer drug development.

“What’s really neat about the I-SPY trial is that Laura Esserman, the PI of the trial, is a breast cancer surgeon here at UCSF and has added so much value to the project because she sees patients early and has a unique opportunity to offer neoadjuvant therapy.

Patients are getting their primary therapy before they get surgery, so for imaging and biomarkers – either established or exploratory – it is a fantastic opportunity. The endpoint is pathological complete response, so you can see if the tumour has disappeared or not.”

Treatment with therapeutics prior to surgery is known as neoadjuvant therapy and has a much shorter time span (around a year) for collecting results than adjuvant trials.  Furthermore, Dr. Hellmann elaborated what is exciting about this new approach:

“It’s a fantastic rapid readout model so you can get answers much more quickly in a year, including pathological specimens, along with the answers from biomarkers and imaging, which are important.”

The FDA has allowed a master IND agreement for this study, so it will be possible to move agents in and out of the trial quickly. So if agent A looks promising it can be advanced quickly and more patients put on it, but if agent B looks toxic, it can be discarded quickly. It’s not just a clinical trial, but a experimental trial process that gives you a rapid readout of whether the agent works or not.

The hope is that you won’t be wasting time and money in phase III trials, but most importantly, patients experience on that molecule.  If the answer is yes on I-SPY, you then have a biomarker hypothesis for that agent and can then do a more traditional phase III trial having increased your chances of success.

In this way, we will also learn more about the biology of the cancer and effectiveness of the treatments earlier in the course of the disease, which may lead to better long term survival than if treatment is delayed to the later stage of disease, when the cancer has spread and metastasised.

You can find out more about the clinical trial process here and here.

The trial will look at the following protocol:

Source: I-SPY2.org

For breast cancer, the standard of care is paclitaxel followed by four cycles of anthracycline therapy.  In this model, women with breast cancer can also receive other therapies, either marketed or investigational, to see if their outcome can be improved. For this I-SPY2 project, the five initial investigational agents are provided by Pfizer, Abbott and Amgen:

1. ABT-888 (veliparib) from Abbott, is a PARP inhibitor
2. AMG 655 (conatumumab) from Amgen is an APO/TRAIL protein that causes apoptosis
3. AMG 386 from Amgen is a VEGF angiogenesis inhibitor similar to Genentech’s Avastin
4. CP-751,871 (figitumumab) from Pfizer is an IGF-1R inhibitor that targets the insulin receptor
5. HKI-272 (neratinib) from Pfizer is a Pan ErbB inhibitor similar to Herceptin

None of the I-SPY-2 breast cancer project would have been possible without the passion, energy and enthusiasm of women such as Drs Sue Desmond-Hellmann, Laura Esserman or Janet Woodcock of the FDA, who has been pressing for more creative solutions to fast track better cancer drugs for some time.  This consortium is particularly fascinating to watch because it brings together the major players – academia, industry and the FDA, in a way that has never been done before.  We should salute their originality and endeavour to think, and more importantly, do things differently.

If the basic concept proves successful, such a revolutionary clinical trial process may well become the new model for early and more effective drug testing, not only in cancer, but also for other diseases such as alzheimers, diabetes and other chronic diseases. In the long run, this approach may also lead to lower healthcare costs by improving efficiencies.

While Dr Hellmann was excitedly describing the process, I was thinking how much intuitive sense it makes and wished that the bureaucratic hurdles to more collaborative academia-industry-FDA clinical trials had fallen long ago.

The important thing though, is that it’s actually happening right here, right now and for people with cancer, that is good news indeed.

The future of Oncology… is in neoadjuvant therapy and biomarker led trials.