Biotech Strategy Blog

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

Posts tagged ‘Ariad’

After a long lull on the targeted therapies front – outside of EGFR T790M in lung cancer – this year’s ASCO has plenty to be cheerful about with new data across multiple tumour types.  We can’t cover them all here, but more will be discussed in the Daily Live Blogs starting on Saturday.

Which drugs are going to be in roaring back after a quiet period?  Which ones will be having a more muted meeting?

ASCO16 Chicago 4For those of you who are working in the targeting therapy world, take heart, there is a future beyond cancer immunotherapy; it is not the universal panacea and will likely not cure every cancer, at least for now.

There’s still a market opportunity for targeted therapies in cancer, and as we mentioned in yesterday’s ASCO Preview, there is also potential for the combination of targeted therapies with immunotherapies, so long as the combined toxicity is manageable and doesn’t outweigh the benefits.

In this post we’re looking at a selection of targeted therapies in a variety of tumour types. There’s a lot to choose from at ASCO this year.

Here’s a few we think are worth highlighting upfront.

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With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:

“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”

Good question.

There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.

Reading Market Philly Chocolate TowerTo maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.

When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!

I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research.  Thank you for joining our conference coverage service, we really appreciate it.

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It’s a while since we discussed ALK+ lung cancer, but with new data coming out at ESMO last week, this is a good time to take stock and see what’s happening with the next generation inhibitors in a post crizotinib (Xalkori) world. These include ceritinib (Zykadia), alectinib and Ariad’s AP26113, which just received Breakthrough Therapy Designation from the FDA.

At ESMO two years ago in Milan, it was quite clear in a dedicated ALK session that these agents not only looked very promising, but were also likely to be fast tracked to market in patients with crizotinib resistance. All are more potent (based on the IC50) than crizotinib, while some target point mutations associated with crizotinib resistance and others have activity in patients with brain metastases, which is one of the common causes of progressive disease with crizotinib.

Today’s post is a long and meaty one – it not only covers data that was presented at the meeting, but also offers a glimpse into the changing ALK landscape.

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In my final post from the 2013 annual meeting of the American Association for Cancer Research (AACR), I wanted to share some more reflections from my time in the poster sessions. It’s certainly not all mice, and test tubes, and there were some interesting data from biotechnology companies to consider.

Sometimes the data presented is completely new, other times if you are following a product or company you can see the next stage of development and track progress. AACR posters are often not available if you don’t attend the meeting.

Additionally companies use AACR to showcase potential early licensing opportunities and new targets, so like Bitcoins a few nuggets can be mined from the meeting.  Here are a few examples of what the AACR poster sessions had to offer from a biotech perspective.

Gilead $GILD – Following a new combination

At the 2012 American Society of Hematology (ASH) annual meeting in Atlanta last year, Russell Burke and colleagues from the Knight Cancer Institute at OHSU (Brian Druker’s lab) presented a poster (abstract 3876) on the rational for Combining idelalisib (GS-1101/CAL-101), a PI3 kinase delta (PI3Kδ) inhibitor and a novel highly selective Spleen tyrosine kinase (Syk) inhibitor, GS-9973. In their abstract they noted that,

Simultaneous inhibition of multiple pathways downstream of the BCR [B-cell receptor] has the potential to result in a synergistic response that may overcome the resistance observed with single compound use” 

Furthermore, they also demonstrated that,

both PI3Kδ and Syk inhibition reduces CLL survival” and that “combination therapy targeting both PI3Kd and Syk may provide a novel treatment approach, especially in patients with poor risk disease that may not respond optimally to single agents.”

This year at the AACR annual meeting, a Gilead poster (abstract  26) evaluated the safety, pharmacokinetics and pharmacodynamics of this combination in female healthy subjects.  The poster concluded:

  • Co-administration of GS-9973 with idelalisib displayed markedly higher PD effect vs. either agent alone.
  • Overall, GS-9973 and idelalisib were well tolerated when administered in combination or alone.
  • Phase 2 studies in B cell hematologic malignancies evaluating GS-9973 + idelalisib are ongoing.

We will most likely have to wait to ASH meeting later this year in New Orleans to see what the clinical benefit of this combination is, but you can see how you can follow progress from a poster at ASH, to a poster at AACR and then a phase II or III clinical trial presentation at ASH or ASCO in the future.

Ariad $ARIA – a new potential target for ponatinib?

Ponatinib (Iclusig) is a multi-targeted tyrosine kinase inhibitor (TKI) of several targets including Bcr-Abl, FGFR, ALK and RET.  Several posters were presented at AACR last week.  In one that caught my attention (abstract 2084), Ariad researchers showed it is a highly potent inhibitor of activated variants of RET Kinase, which is often dysregulated in medullary thyroid cancer (MTC) and non-small cell lung cancer (NSCLC).

Vandetanib ($AZN) and cabozantinib ($EXEL) are other multi-kinase inhibitors that received FDA approval in the last year or two for MTC, albeit in different lines of therapy, so the activity of other TKI’s in MTC should not come as a surprise.

The Ariad poster demonstrated the preclinical activity of ponatinib over other TKI’s in variants of RET in MTC and NSCLC.  The poster concluded:

These results provide strong support for the clinical evaluation of ponatinib in patients with RET-driven cancers.”

From a scientific rational the above statement makes sense, but from a commercial perspective it’s more questionable if this were the lead indication.  However, it could make strategic sense to add on small niche indications for a compound that is generating its primary revenue elsewhere.

The challenge is that the medullary thyroid cancer market is not large especially in the relapse setting, as Exelisis have found, plus the tumour is a slow growing one.  While NSCLC sounds promising, the number of NSCLC patients with RET is small (~1%).

This means it will most likely require the screening hundreds of patients to find one patient with RET into a clinical trial, assuming they are willing and meet the inclusion criteria.  This is likely to be an expensive and time-consuming process, so the commercial rational will need to be carefully considered.

BioMarin $BMRN – a prostate cancer licensing opportunity or a “dead donkey”?

Companies also use posters at AACR to showcase potential licensing opportunities and one example I came across was BioMarin’s poster (abstract 2049) for BMN860 a novel CYP17 inhibitor.  Based on some limited preclinical data that showed BMN860 to be more potent than abiraterone acetate (Zytiga), the company are seeking to license out their compound.

Interestingly, the BioMarin poster showed no data comparing BMN860 to other second-generation CYP17 inhibitors such as TAK-700 (orteronel), and the presenter admitted they had no plans to do further preclinical work on it themselves.

Given the costs of bringing a new prostate cancer drug to market and the uncertainty of the market opportunity in the face of generic abiraterone and competition from other CYP17 inhibitors far head in development, it’s hard to see the commercial opportunity for BMN860.

If you are a Pharma BDL professional looking to in-license a novel CYP17 inhibitor, then BioMarin do have one on offer.  However, for those used to British vernacular, it struck me as a “dead donkey” being too little too late to really capitalise on the market opportunity.

This is the end of my coverage of AACR 2013.  I am looking forward to the AACR-EORTC-NCI Molecular Targets and Cancer Therapeutics meeting in Boston later this year.  Given the focus of Boston biotech on cancer drug development, I expect this to be a high quality meeting.

If you are interested in more coverage from AACR 2013, I encourage you to check out Pharma Strategy Blog, which will have some in-depth pieces in the coming days.

The Yonhap news agency announced today that the South Korean equivalent of the FDA had approved Il-Yang pharmaceuticals radotinib (brand name Supect) for chronic myeloid leukemia (CML).  Radotinib is a tyrosine kinase inhibitor, also known by its development code of IY5511.

I briefly mentioned radotinib in my CML update from the ASH 2011 annual meeting.

The Yonhap release quotes an official at the Korean Centers for Disease Control and Prevention (KCDC) as saying that:

“It will be used on patients who have become resistant to existing drugs such as Gleevec, Tasigna and Sprycel.”

While its use in Korea appears to be in second or third line & non-responding patients, the Yonhap release states that “Il-Yang have started additional clinical trials in South Korea, India, Thailand and Indonesia,” and the intention in those countries appears to be directed to front line use.

No mention is made of China or Brazil, but the fact that Il-Yang are focusing on the emerging markets of Asia, does not rule out that this drug might finder wider use outside of the countries where clinical trials have taken place.  I could certainly see generic companies interested in potential licensing opportunities.

Details of the price of Supect (not a name I particularly like, I have to say – suggests “Suspect” but I am sure the name translates better in other languages) are unknown. Il-Yang are quoted in the Yonhap release as saying that it will be priced cheaper than existing CML drugs.

Could Supect be a competitor to Ariad’s ponatinib? I am sure there will be more information released as to which mutations it targets, but it’s a product that has largely flown under the radar.  I have not seen any presentations at recent EHA or ASH annual meetings.  Even if it is more closer to imatinib than ponatinib in terms of efficacy, its launch may have an impact on the future ponatinib pricing strategy.

Will Novartis and BMS compete on price in Korea and other Asian markets? It will be interesting to watch whether they see Supect as serious competition.  With the prospect of generic imatinib in a few years time, radotinib may have just made it to market in time.

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