Biotech Strategy Blog

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

Posts tagged ‘bevacizumab’

The 2016 Congress of the European Society for Medical Oncology (ESMO) is fast approaching. It takes place next month from October 7th to 11th and we will be on site covering the meeting for Biotech Strategy Blog. We’re looking forward to a great meeting!

ESMO 2016 CongressIf you are sitting on the fence as to whether you should go to Copenhagen, then hopefully our series of Previews will help you decide.

Be warned that accommodation is in already in short supply and ESMO are now putting people up across the Oresund bridge in Malmo, Sweden.

The Congress App has a lot of useful information and is well worth downloading, if you haven’t done so already.

Last week many of the late breaking abstract (LBA) titles were announced, although there are still some placeholders. While we won’t know the actual late-breaking data until the meeting, the LBA titles offer insights into what will be presented in Copenhagen.

In the second in our ESMO 2016 Preview series, we’re highlighting the lung cancer late breakers that we’re looking forward to hearing, providing some background on why they may be of interest, and a look at how some of subset landscapes may be a-changing in the future.

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Tesaro’s niraparib is a highly selective poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor that can induce synthetic lethality in tumor cells with homologous recombination DNA repair deficiencies (HRD), including germline BRCA-mutated tumours.  It received a lot of attention yesterday following the company’s announcement that the phase 3 trial successfully met its primary endpoint.  The trial was expected to readout this month, so it was bang on schedule.

ASCO 2016 Posters 5

Braving the scrum in the ASCO 2016 poster hall

The results generated a lot of discussion and also a bunch (half a dozen!) of questions from readers, since there was a lot noise around the top-line data in the press release, but very little real analysis or context.

I was planning on rolling out the draft posts we have been working on Gems from the Poster Halls, which included one focused on ovarian cancer.  It therefore makes sense to combine the poster analysis with a reader Q&A on ovarian cancer, including a detailed look at Tesaro’s niraparib as there are some important subtleties that many have missed.

Inevitably this ended up as a rather meaty analysis rather than the quick review I originally intended!

To learn more about the latest developments in PARP inhibitors and the ovarian cancer landscape, you can sign-in or sign-up in the box below…

One of the (many) highlights for me at the recent annual meeting of the American Association for Cancer Research (AACR) was a “Meet the Expert” session presented by Professor George Coukos.

Prof George Coukos AACR 2016

Prof George Coukos AACR 2016

Professor Coukos is Director of Oncology at the University Hospital of Lausanne and Director of the Ludwig Institute for Cancer Research in Switzerland.

Ovarian cancer is becoming a fascinating battleground for cancer immunotherapy, with multiple challenges that must be overcome before we see improvements in outcomes, especially for women advanced disease.

The interview with Prof Coukos is a follow-on to the one we did on advanced ovarian cancer and checkpoint blockade at ECCO 2015 in Vienna with Dr Nora Disis (Link).

If you missed it, you can still listen to highlights in Episode 7 of the Novel Targets Podcast (Link).

After his AACR presentation, Prof Coukos kindly spoke with BSB and in a wide ranging discussion, highlighted some of the innovative clinical trial strategies he is working on to move the cancer immunotherapy field forward in ovarian cancer.

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Driving St Charles StreetcarAfter exploring the science behind chemotherapy improving T cell trafficking into the tumour yesterday – which is one of the key rate limiting issues that need to be addressed with immunotherapies such as checkpoint blockade – some obvious follow-up questions comes to mind:

  1. Does the compelling data in mice translate to humans?
  2. Can chemotherapy turn a cold tumour into a hot one?
  3. Will patients have improved outcomes as a result – or not?

It’s easy to dismiss traditional therapies in favour of appealing new developments, but what happens when we combine them?  Do we get additive effects, synergies or a negative impact?

As part of our ongoing AACR coverage, we explored this conundrum in the context of new data readouts, as well as the broader competitive landscape.

What we found was really interesting!

BMS, Merck and Genentech/Roche all have trials ongoing in the metastatic colorectal cancer space, with very different approaches being taken.  Does it matter?  Which one’s driving the bus?  We summarise these trials and offer some strategic insights on this niche.

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New developments in renal cell carcinoma

Continuing our focus on genitourinary (GU) cancers this week, today we turn our focus from prostate cancer to renal cell carcinoma (RCC).

There were two important announcments on Monday this week relating to renal carcinoma.

Firstly, Exelixis announced positive top line data from a phase 3 pivotal trial of cabozantinib versus everolimus in relapsed metastatic renal cell carcinoma (METEOR).  The study met the primary endpoint (i.e. significantly improved progression free survival) and the company revealed the following data:

  • Cabozantinib reduced the risk of disease progression or death by 42%; Hazard Ratio = 0.58, (p < 0.0001) compared to everolimus
  • Interim Analysis of OS demonstrated a trend in favour of cabozantinib; Hazard Ratio = 0.67, (p = 0.005) compared to everolimus
  • Exelixis to complete US and EU regulatory filings in early 2016

Secondly, a press release from BMS highlighted the phase 3 CHECKMATE–025 trial comparing nivolumab to everolimus, also in relapsed metastatic RCC, where the independent Data Monitoring Committee recommended early stoppage on the basis of the primary endpoint (OS) being met. The company likely be seeking discussions with Health Authorities with a view to filing the data with the FDA and EMA.

There are some interesting points that fall out of these releases. To learn more, subscribers can log-in below or you can purchase a subscription in the box below.

We hope that everyone had a relaxing holiday break and now it’s time to get back to work.  Tomorrow I will review some more of my thoughts in the immuno-oncology space, since that area had a tremendous amount of progress in San Diego with lots of new ideas to process and summarise.

In the meantime, a few people have written in and asked about what was happening with overcoming resistance in various tumour types, was there anything new to say in that space that was in addition to the the detailed previews we covered before the conference?

Actually, there was a quite a few posters and presentations that caught my eye, so I thought this would be a good idea to review them here:

Lung Cancer: HER2, VEGF, T790M, EGFR, erlotinib, gefitinib, trastuzumab, bevacizumab, CO-1686, AZD9291

Prostate Cancer: mTOR, PI3K, Androgen Receptor, enzalutamide, abiraterone, CC214–2, ARN–509, BET Bromodomian inhibition, ODM–201, GDC–0980, GDC-0068, PF–04691502, BKM120, BEZ235

In the second part of our mini-series on immuno-oncology, I thought it would be a nice idea to share a recent interview conducted with one of Roche/Genentech’s leading researchers in this field.  I was particularly interested in their approach because while BMS and Merck have clearly focused on anti-PD-1, Roche and Genentech have effectively zigged with their development of an anti-PD-L1 inhibitor.  Does this matter?

Here, we explore the general background to this approach and, in particular, where the company are going with their anti-PD-L1 inhibitor, MPDL3280A.

Topics discussed:

anti-PD-L1, anti-PD-1, anti-CTLA-4, checkpoint point inhibitors, T cells, biomarkers.

Drugs mentioned:

MPDL3280A, nivolumab, MK-3475, ipilimumab (Yervoy), lirilumab, BMS-986016 (anti-LAG3), bevacizumab (Avastin), erlotinib (Tarceva), vemurafenib (Zelboraf), cobimetinib.

If you are interested in more background on how the PD-1 and PD-L1 inhibitors work, you can check out the mechanism of action (MOA) in our video preview from ASCO last year, which explains this in fairly simple terms.

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Breaking news:

The New England Journal of Medicine have just published online the results of the Comparison of Age-related macular degeneration treatment trial (CATT) comparing the efficacy of FDA approved ranibizumab (Lucentis) to off-label bevacizumab (Avastin); a trial that has important commercial importance given the comparative costs of an intravitreal injection of around $1950 (Lucentis) vs. $50 (Avastin).

Key Study Results

Based on 1208 patients randomly assigned in the single-blind noninferiority trial, primary outcome was mean change in visual acuity between baseline and 1 year. This was equivalent between the two drugs.

Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively.

Secondary outcome measures included the incidence of ocular and systemic side effects, the results show some similarities and differences:

Rates of death, myocardial infarction and stroke were similar for patients receiving either bevacizumab or ranibizumab (P>0.20).

The proportion of patients with serious adverse events (primarily hospitalization) was higher with bevacizumab than with ranibizumab (24.1% vs 19%)

The conclusion of the study is that:

At 1 year, bevacizumab and ranibizumab had equivalent effects on visual acuity when administered to the same schedule”

However, here is the potential ‘get out’ for Genentech:

Differences in rates of serious adverse events require further study.

The investigators note that the difference in serious adverse events may be due to:

“chance, imbalances in baseline health status that were not included in the medical history or multivariate models, or a true difference in risk.”

i.e. they don’t know.

What the results from the CATT study mean is that Avastin and Lucentis are similar, but different. That is not a surprising result given that they originate from the same anti-VEGF monoclonal antibody.  However, they are not identical.

Clearly, if I were a patient, the additional 5% risk of serious adverse events would have to be weighed against the cost benefits. For those who are uninsured or unable to afford Lucentis, receiving Avastin may be an informed decision worth taking.  As the investigators note:

One of the many factors that contribute to the selection of a drug for a patient is cost.  A single dose of ranibizumab costs 40 times as much as a single dose of bevacizumab.  This cost differential has important economic implications when extrapolated to the more than 250,000 patients who are treated for neovascular AMD annually in the United States.

I look forward to hearing the animated discussion of these results at the ARVO annual meeting in Fort Lauderdale on Sunday.

ResearchBlogging.orgThe CATT Research Group (2011). Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration New England Journal of Medicine DOI: 10.1056/NEJMoa1102673

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This weekend I will be at the annual meeting of The Association for Research in Vision and Ophthalmology (ARVO) in Fort Lauderdale.

I’m excited about attending because earlier in my career I worked at Alcon Laboratories on European IDE clinical trials for three novel intra-ocular lenses.

ARVO is the ophthalmology equivalent of AACR and is where scientists involved in drug, device research meet to discuss new findings and early stage research.

The title of meeting is “Visionary Genomics.”  After listening to the plenary session at the recent AACR annual meeting by Lynda Chin on how insights from cancer genomics are translating into personalized medicine, I’m looking forward to seeing the impact of genomics on vision research.

Sunday’s ARVO/Alcon keynote presentation is from Roderick McInnes who is the Canada Research Chair in Neurogenetics at McGill University in Montreal.

A presentation that is already generating some advance interest is Sunday’s presentation of the results from the Comparison of Age Related Macular Degeneration Treatments Trials (CATT).

Age related macular degeneration (AMD) is the leading cause of vision loss in those over 65 in the United States, with over 7 million people estimated to be at risk.  Once you have AMD in one eye, you have a 43% risk of developing it in the other eye over a  five year period, a scary statistic!

The first CATT clinical trial is between bevacizumab (Avastin®) and ranibizumab (Lucentis®), both similar anti-VEGF inhibitors that are derived from the same monoclonal antibody.  It will be interesting to see whether the data supports the current practice of off-label use of bevacizumab given its lower cost compared to ranibizumab.

The findings from this data will also potentially impact aflibercept (VEGF-Trap) that is being co-developed by Bayer and Regeneron.  In February, Regeneron submitted a biologics license application (BLA) to the FDA for the use of VEGF-Trap in wet AMD.

The initial results from the aflibercept phase III AMD trial announced late last year showed a non-inferiority to ranibizumab.  If aflibercept is approved and comes to market in 2012, depending on the CATT results, it may have to compete on price against off-label bevacizumab in AMD.  Whether a more convenient injection once every two months for VEGF-Trap (compared to monthly for Lucentis) is sufficient to justify a price premium, it will be interesting to watch the market dynamics in this space.

You can find more about the meeting on the ARVO conference website and they have also put up a blog for the meeting.   The theme of my blog posts over the next few days will be ophthalmology related, and I expect to be live tweeting from ARVO 2011 on Sunday and Monday.  I’ll also be aggregating tweets from the meeting (hashtag #ARVO11) on this blog.


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