Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology & Hematology

Posts tagged ‘AACR’

There are quite a few posters at the forthcoming AACR-NCI-EORTC Molecular Targets meeting this weekend that I wanted to highlight as potentially interesting and will additionally review in more depth once they have been published.

Please note: None of the embargoed abstracts are covered here in this preview to avoid any complications, but more detailed notes and reports will follow later on these from the conference as they are published.

Here some of the abstracts that caught my eye, in no particular order:

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Chicago – At the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Charles L Sawyers, MD, President of the American Association for Cancer Research (AACR) and one of the United States leading cancer researchers, told the 30,000 meeting attendees in the plenary session that we need to get to combination therapy faster in order to overcome cancer drug resistance.

Charles L. Sawyers, MD gives 2013 Science of Oncology Award Lecture at ASCO annual meeting

In his Science of Oncology Award lecture entitled “Overcoming Resistance to Cancer Drug Therapy,” he told the audience that drug resistance is universal. It represents one of the key challenges in cancer treatment. A patient may obtain a dramatic response on a new treatment, but as the cancer finds escape routes among the network of cellular signaling pathways, resistance to the drug is acquired and the cancer reappears.

You can read a previous interview with Dr Sawyers on Pharma Strategy Blog.

Daniel O’Day, COO of Roche Pharmaceuticals, referred to Dr Sawyers’ ASCO lecture at a corporate event in Chicago. He told analysts that a key future strategy for Roche will be improving cancer treatment with combinations. The ability to bring effective combinations to market faster will favor large companies such as Roche who have a robust pipeline of cancer drugs in development. You can see Genentech’s perspective on this via a well thought out post from their VP of Clinical Development, Chris Bowden.

The other advantage of a broad robust pipeline for large Pharma is the ability to leverage this strategically and globally as the reimbursement landscape changes. In the HER2 arena, for example, Roche could hold the price of Perjeta while offering discounts to Herceptin, thereby offering a lower price for the combination that might be attractive to purchasers. In Europe, this kind of creative bargaining is becoming more common in the approval process as Health Authorities seek to reduce costs and find more affordable options before giving approval for new drugs in their market.

Dr Sawyers talk was one of the highlights of ASCO 2013 for me.  I captured the essence of his presentation from the many tweets that took place as it was presented. Here’s a link to the Storify.

 

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A scientific meeting that I would have liked to have attended and one where I think attendees will obtain a lot of insight into the future of prostate cancer research is the forthcoming American Association for Cancer Research (AACR) Advances in Prostate Cancer Research meeting.

AACR Advances in Prostate Cancer Research Meeting 2012Chaired by Charles Sawyers (MSKCC) and Arul Chinnayan (Michigan) it has an impressive line-up of speakers and sessions.  The meeting takes place next week (Feb 6-9) in Orlando.

There are two presentations on cabozantib (XL184) that may offer new insights into the mechanism of action of the drug and its potential:

Cabozantinib (XL-184) and prostate cancer: Preclinical and clinical profile of a novel agent

Maha Hussain, University of Michigan Medical School, Ann Arbor, MI

Cabozantinib (XL184) inhibits androgen-sensitive and castration-resistant prostate cancer in the bone and increases bone formation in non-tumored bones
Eva Corey, University of Washington, Seattle, WA

A few of the presentations at the meeting that caught my attention include:

  • Role of inflammation (William Nelson)
  • Influence of tumor microenvironment on progression and resistance (Christopher Logothetis),
  • Novel therapeutic targets in prostate cancer (Arul Chinnaiyan)
  • Overcoming castration-resistant prostate cancer 
(Charles Sawyers)

If you have in an interest in prostate cancer research, February 6-9 in Orlando is the place to be.

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The 102nd Annual meeting of the American Association for Cancer Research (AACR) ended yesterday in Orlando, and it was only the diehards who kept going till the last session of the last day for an update on “Novel Androgen Receptor Antagonists.”

As I mentioned in an earlier post, there is a lot of excitement in the prostate cancer field at the moment with three new therapies approved last year (cabazitaxel, sipuleucel-T, denosumab), and more expected over the next two years (abiraterone acetate, MDV3100, cabozantinib/XL-184).

What I took from the AACR session I attended, is that there are also other products in the pipeline that are worth watching.  Below is a list of some of the products that were mentioned. It’s not intended to be a comprehensive review of the prostate cancer landscape, only my notes and thoughts on some of the new products that the speakers touched upon.

Abiraterone Acetate: The postive phase III trial results were reported last year at ESMO and ASCO GU, and the approval of this drug is currently being considered by the FDA.  Approval is expected shortly, and possibly in time for launch at the forthcoming annual meeting of the American Urological Association (AUA) meeting in Washington, DC.

Abiraterone (brand name Zytiga) inhibits the enzymes (17-alpha hydroxylase and C17, 20 lyase) responsible for adrenal androgen formation.

The phase III results were impressive in very sick patients who were close to the end of their lives in very advanced disease.  Overall survival increased from 10.9 to 14.8 months in the second line chemotherapy setting post docetaxel.  It’s expected that the results will be more dramatic pre-chemotherapy.

Once the FDA approval is obtained, it’s hard to see how oncologists will not consider abiraterone instead of cabazitaxel in the second-line chemotherapy setting.  An easily taken pill with fewer less side effects may be a more convenient option for elderly or frail men with prostate cancer.  Abiraterone’s approval will not be good news for sanofi-aventis.

I also expect we will see significantly off-label usage of abiraterone pre-chemotherapy by urologists as they seek to maintain hormone-sensitivity in their patients after several lines of anti-hormonal therapies.  There is a phase III trial ongoing in this setting that is expected to show promising data by the end of the year.

However, it’s a good strategy to come market as soon as possible to provide wider access to patients in need, and the post-docetaxel second line setting allowed the overall survival benefit to be shown before the pre-chemo data would be available.

However, what I learned at the meeting is that abiraterone acetate may not be the best product in the long term.  Currently it requires the corticosteroid, prednisone, to be given at the same time to attenuate the mineralocorticoid effects.  Questions that were raised in the AACR session about long-term treatment with abiraterone included, “Must a corticosteroid be given concurrently?” and “What about hypertension?”

Other questions remain, such as possible development of resistance to abiraterone. Often the first drug to market is not the best, and it’s possible that second generation new products in the pipeline may be better than abiraterone and delay the time to resistance further.

However, what abiraterone does have is first mover advantage and depending on the pricing strategy adopted by Johnson & Johnson, the ability to capture market share earlier.  It will be interesting to see what happens with this drug, but it’s certainly an exciting time for patients with prostate cancer.

TAK-700: This drug from Takeda/Millennium is a more potent inhibitor of C17α-hydroxylase than abiraterone.  One of the panelists at AACR believed that TAK-700 “may in the long run surplant abiraterone acetate due to less need for mineralocorticoids.” TAK 700 entered phase III clinical trials late last year.

MDV3100:  This drug is being developed by Medivation/Astellas and is also in phase III trials, with data expected by the end of this year or early 2012.  It has a high affinity for the androgen receptor. However, what came across in the AACR presentation by Howard Scher, was his view that the second compound developed by Charles Sawyers, ARN-509 may be better than MDV3100.

ARN-509: This drug from Aragon Pharmaceuticals is in phase I/II clinical trials and is definitely one to watch.  As Dr Scher pointed out, ARN-509 is more potent than MDV3100 and I expect we will see publication of more data on ARN-509 in the near future.

If you are interested in prostate cancer, AACR are offering webcasts and podcasts of scientific sessions this year.  Further information can be found on their website.  AACR have also announced a scientific special session on “Advances in Prostate Cancer Research” from February 6-9 2012.  It’s certainly an interesting and exciting time in this field as new products become available, something that is likely to make a real difference to how this disease is treated.

 

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Faced with the opportunity to read around 900+ posters yesterday afternoon in the first of the six main poster sessions from Sunday to Wednesday here at the AACR annual meeting, any selection of a “poster of the day” is extremely subjective.  All the posters here have considerable scientific merit having passed a rigorous peer-review selection process.

Faced with a smorgasboard of choice, one ends up focusing on areas of personal interest. One area I have recently started to write about on this blog is the impact nanotechnology may have on cancer research and in particular how nanoparticles in the form of diamonds can be used to reach into tumors.

So “my poster of the day” from Sunday April 3rd, Day 2 of AACR is  “Multistate Nanoparticle Delivery System for Deep Penetration into Tumor Tissue.” It is Abstract#548 on the AACR website, and is from a team of researchers at the Department of Chemistry at MIT, Massachusetts General Hospital and Harvard Medical School.

The published poster by Cliff Wong and colleagues is “a proof-of-principle demonstration that a size changing nanoparticle can facilitate delivery into the dense collagen matrix of a tumor.

The authors conclude, that what they have developed is: “the potential for customized delivery of nanoparticles by using genomic and molecular data to achieve optimal delivery for a particular patient.”

Heralding the future potential of their research, the poster states that as result of this work they now can “design a series of customized nanoparticles that are activated by a variety of tumor-associated proteases such as cathepsin B and urokinase plasminogen activator (uPA).

One question that this research raises to me is to what extent different tumors may require a different sized nanoparticles to deliver drug to the target area? If we do need different sized nanoparticles, then how do we determine which is the best size/combination?

I’m excited at the possibility that not only may we have personalized medicine, but that nanotechnology may enable customized drug delivery.

The heart of the AACR annual meeting to me is the posters, and they frequently stimulate questions that may generate novel new approaches or trigger new research avenues or opportunities to make a difference in the lives of future cancer patients.

 

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There are 5,396 posters at the 102nd Annual Meeting of the American Association for Cancer Research (AACR) here in Orlando. Intermingled with the exhibitors (something that no doubt encourages traffic to the exhibits), the posters provide a window into the world of current cancer research and the spirit of collaboration.

Researchers from all over the world present their latest scientific discoveries, what they may have spent 3 years or more years on while studying for a Ph.D or undertaking a post-doctoral fellowship.

The research is innovative, and what’s seen at AACR is often at the cutting edge and shown prior to publication in a major journal.

What is palpable is the energy surrounding the poster discussions as experts, thought leaders and leading researchers network and share ideas with typically more junior colleagues, and in the process relate their experience to the poster being presented.

In a world of fixed term grants, the poster session is also an opportunity to showcase research to those who may be looking to hire new talent to their team.

It takes six poster sessions over four days for the 5000+ posters to be presented. I’m looking forward to the exercise!

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It’s a busy day of science at the 102nd American Association for Cancer Research (AACR) annual meeting in Orlando, You can follow what’s happening on twitter, #AACR.  Pharma Strategy Blog has an excellent “Cover it Live” widget that shows everyone’s #AACR tweets. It allows you to go back in time, so you can see what happened earlier.  AACR also has some excellent webcasts and podcasts from the meeting.

However, what caught my attention this morning was the launch of a new journal, Cancer Discovery; preview copies were handed out to attendees at the plenary session this morning.

In a world where we are already overwhelmed by data, publications and sources of information, why is this journal both important and worth reading?

Firstly, this team has a distinguished group of editors, Lewis Cantley, PhD and José Baselga MD PhD are Editors-in-Chief.  However, what attracted me was the way this journal, in a highly readable way, covers a wide range of topics from news, updates on current research to mini reviews and research articles.

In the news section, the journal picked up on nanodiamonds for drug delivery (a topic previously mentioned on this blog), and discussed the Gilead acquisition of Calistoga from perspective of bringing PI3K delta inhibitors to market.

I liked the selected highlights of recent articles of exceptional significance from the cancer literature.  The mini review on the “stumbling blocks on the path to personalized medicine in Breast Cancer” summarized the challenges in the clinical development of PARP inhibitors. The research articles reminded me of those I’ve read in other journals such as Science, with high quality figures and tables.

If AACR and the editors can keep up the high standard of the April 2011 preview copy they have published, Cancer Discovery will definitely be on the reading list of those involved with cancer research, new product development and translational medicine.

You can find out more about Cancer Discovery and read online articles on the AACR website.

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In an acquisition that highlights the importance of cancer and inflammation, Gilead Sciences today announced the acquisition of Seattle based Calistoga Pharmaceuticals for $375M.

Calistoga’s pipeline is focused on the development of PI3 kinase inhibitors for cancer and inflammation. Sally Church on Pharma Strategy Blog has written extensively about “The potential of the PI3K pathway inhibitors in lung cancer”, and discussed Calistoga’s CAL-101 compound and its development for hematological malignancies in her report on “What’s hot at ASH in 2010”.

I encourage you to read (if you already don’t) Sally’s excellent Pharma Strategy Blog for further information on the science and mechanism of action of the PI3K pathway (way beyond my pay grade) and her view on CAL-101’s potential.

Sally will also be at the timely AACR meeting on targeting PI3K/mTOR signaling in cancer that is being held in San Francisco later this week.

What makes CAL-101 interesting to me is its potential in targeting inflammatory mediators. CAL-101 is a first in class PI3K delta specific inhibitor; the delta isoform of phosphoinositide-3 kinase (PI3K) is expressed in leukocytes involved with a variety of inflammatory, autoimmune and hematological cancers. Increasingly I think we will see companies investigating the cross-talk between inflammation and other diseases.

In addition to the upfront payment of $375M, there are potential milestone payments of $225M.  The deal is set to close in the second quarter of 2011.

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