Biotech Strategy Blog

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

Posts tagged ‘avastin’

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.

To learn more, subscribers can log-in or you can sign-up in the blue box below…

Ovarian cancer is an often neglected area in cancer drug development and historically has often been one of the last solid tumours to be evaluated as part of a life cycle management program. There are a number of reasons for this, but recently that situation has begun to change as our knowledge of the underlying biology improves and new agents are developed that target the particular oncogenic aberrations.

It is a tumour type that ranks 5th in cancer deaths amongst women and accounts for more deaths than any other gynaecologic cancer. Indeed, in 2014 nearly 22,000 women are estimated to be diagnosed with this cancer in the U.S. and approx. 14,000 will likely die from the disease.

Earlier this month the FDA approved bevacizumab (Avastin) in combination with chemotherapy (paclitaxel plus pegylated liposomal doxorubicin or topetecan) for the treatment of platinum-resistant, recurrent epithelial ovarian cancer (EOC), fallopian tube, or primary peritoneal cancer who have received no more than two prior therapies. The approval was based on the phase 3 AURELIA trial (n=361), which demonstrated an improvement in median progression free survival (PFS) of 6.8 vs. 3.4 months (HR 0.38, P<0.0001). This means that the women in the trial saw a 62% reduction in the risk of their symptoms worsening compared to chemotherapy alone.

Surprisingly, this advance represented the first new treatment option in this setting for 15 years!

The good news is that beyond Avastin, there are a number of other promising agents in development for ovarian cancer. At this year’s EORTC-AACR-NCI Molecular Targets meeting held in Barcelona, new data was presented on several such compounds that are well worth highlighting.

To learn more about these therapies, you can sign in or sign up below.

Sometimes timing can be amusing when writing up data and conferences. Yesterday, while writing about the immuno-oncology developments in renal cell cancer (RCC), I was putting a table of the trials together and absent mindedly noticed that Merck didn’t have much going in this indication compared to BMS and Roche/Genentech.

Oddly, the company fixed that this morning with their announcement that they are expanding their combinations and collaborations for the anti-PD–1 antibody, MK–3475. One of the new trials includes a partnership with Pfizer for axitinib (Inlyta), enabling them to study a PD–1 + VEGF combination in RCC. The table in yesterday’s thought piece has now been updated to include this trial, although it is in the planning stage at present.

Today, I want to switch horses a little bit and talk about another immuno-oncology therapy, namely, ipilimumab (Yervoy).  Dr Charles Drake (Johns Hopkins) presented an update on the post chemotherapy trial (CA184–083) in CRPC at ASCO GU this weekend, which we wrote about from ESMO last Fall when the data was first presented (see here).  What’s interesting is that the trial, although negative, only just missed its endpoint.

Last week I came across some interesting new developments relating to ipilimumab that are well worth discussing here, particularly in relation to biomarkers, as they may have significant implications for the drug clinically.

To read our analysis on ipilimumab, you can sign up or sign in below.

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.

To access the interview on PD-L1, you can sign in or sign up in the box below.

The 2014 ASCO Gastrointestinal (GI) Cancer Symposium takes place in San Francisco from Jan 16-18 and is the second meeting in this year’s oncology conference calendar. GI cancers include oesophageal, gastric, colorectal and pancreatic cancers, as well as hepatocarcinoma or HCC (liver).

You can follow any tweets from ASCO GI using the hashtag #GI14.

This year, the topics that most caught my eye in the program were pancreatic and gastric cancers.

This post provides insights on the key studies that looked interesting to me at this event, based on the schedule available.  The abstracts will be available on January 14th and can be accessed here.

Companies mentioned: Celgene, Lilly, Roche/Genentech, Aduro Biotech
Drugs mentioned:  Abraxane, Gemzar, ramucirumab, Avastin, Herceptin, GVAX


This afternoon at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in Fort Lauderdale saw the long-awaited briefing on the National Eye Institute Lucentis v Avastin comparative effectiveness trial in AMD.

I wrote in a previous post about the CATT results published in the New England Journal of Medicine.

I also tweeted from the briefing, but must add the disclaimer that live tweeting is tough and none of my tweets should be relied upon for accuracy.

What did I learn from the briefing (aside from the fact that ARVO’s technology vendors have real challenges in not being able to light a room properly, set up wifi and get a projector to work):

  • The CATT study was set-up before anyone knew what the price for Lucentis was.
  • No mention was made in the briefing today about comparative cost – but isn’t that what everyone thinks this study is about?
  • No mention was made of how you balance the cost benefits against the trade-off of the higher risk of serious adverse events that was seen.
  • When asked what they would give to a relative, most of the panel answering Q&A “punted” and said they would discuss the data with the patient, and try and get them to make an informed decision.
  • Only Dan Martin from Cleveland Clinic stuck his neck out and said if the patient asked him to make the choice of what to take, he would use Avastin over Lucentis – this statement clearly resonated with the audience (he received a big round of applause)
  • Two year data is already available and some of it was shown today, with no difference in death rate at 2 years between Lucentis or Avastin. The two year data will be published this time next year.
  • The study was not adequately powered to look at the serious adverse events (SAE), which means the statistically significant difference in SAEs may never be truly understood.

Overall, my impression from the briefing is that Lucentis is not identical to Avastin, although functionally the benefits from both appear broadly comparable with no statistical significance between them in terms of visual acuity gains. No mention was made of when you might use one drug over the other (if at all).

Lucentis did have some benefits over Avastin such as a lower retinal thickness at one year compared to the other three treatment groups, which was statistically significant. Both drugs produced an immediate and substantial decrease in retinal fluid, but more eyes were completely dry with Lucentis.

My thoughts are that the debate over Lucentis v Avastin is like the difference between a brand versus a generic, they are similar in terms of efficacy but not identical. While that’s perhaps an over-simplification given that in this case one drug is FDA approved and the other is not, those who want a brand and can afford it will buy a brand, while others may prefer the “generic” for cost reasons.

Will the Lucentis v Avastin decision be any different? If you can afford Lucentis through your insurance you may choose to take that, otherwise Avastin is another option for AMD.  Weighing cost versus slightly higher risk of SAE’s (for which there’s no adequate explanation showing causality) is how I would approach this decision.

It was interesting to note that the follow-up will continue and two year results will be published this time next year. They may shed further light on the serious adverse event differences, but I suspect that given the way the study is powered, this issue may not be resolved any further.

My overall take is that there is nothing compelling in the data to suggest that any ophthalmologist that is using bevacizumab off-label will switch patients to ranibizumab. Off-label Avastin use in wet AMD received an official NEI endorsement from the CATT study and will continue.

Equally those who are happy with Lucentis will not switch to Avastin on the back of this study, given that the Lucentis data appeared slightly better in places.  The controversy will no doubt continue and other studies comparing Lucentis v Avastin will add further insight.


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

1 Comment

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.


error: Content is protected !!