Biotech Strategy Blog

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

Posts tagged ‘ASCO 2013’

AZD3514 is a novel Selective Androgen Receptor Down-Regulating Drug (SARD) that showed early preclinical promise for the treatment of Castration-Resistant Prostate Cancer (CRPC).

However the development of this drug in advanced prostate cancer has been terminated by AstraZeneca according to Dr Aurelius Omlin, a Clinical Research Fellow at The Royal Marsden Hospital who presented clinical data on AZD3514 at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

I previously wrote about the promising preclinical data for AZD3514 presented by Sarah Loddick at the 2012 annual meeting of the American Association for Cancer Research (AACR) and sometimes drugs when they transition to the clinic just don’t live up to their promise.

That’s what happened here, and it reminds us that testing of drugs on human volunteers remains a key part of drug development despite the inherent risks. (See my post on the TLS deaths on the AbbVie/Genentech ABT-199 CLL dose finding trial)

AZD3514 ASCO 2013 PresentationThe results from a first-in-human clinical trial with in men with CRPC were presented by Dr Omlin at ASCO 2013 (abstract 4511). In his oral presentation, he first noted that:

“AZD3514 is a first-in-class, non-steroidal small molecule androgen receptor (AR) down-regulator that inhibits nuclear AR translocation and results in proteasomal AR protein degradation.”

The phase 1 clinical trial to assess safety and tolerability explored doses ranging from 100mg once daily (OD) to 1000mg OD in capsule formulation, and from 1000mg OD to 2000mg taken twice daily (BID) in tablet formulation. A pretty comprehensive range, but……

“Tolerability of AZD3514 was problematic,” said Omlin. “80% of patients had Grade 1-2 Nausea (n=39 out of 49) and 49% Grade 1-2 Vomiting (n=24 out of 49).”  Additionally, grade 1-2 thrombocytopenia was seen in 33% of patients.  There was no dose limiting toxicity reported.

What killed it for AZD3514 was the fact that according to Omlin,

“Nausea and vomiting were characteristic from the very first dose level starting about 30-60 minutes after dosing and lasting for several hours thereafter.”

However, the drug did show activity in CRPC patients with several patients showing PSA declines including one patient with prior abiraterone exposure.  Two patients with soft tissue disease had confirmed responses according to Recist 1.1. There was also evidence of clinical activity from changes in the number of circulating tumor cells.

Industry analyst, David Miller (@BiotechStockRsr) commented on Twitter, while watching the presentation, that he thought it hard to see the drug progressing in development, and he turned out to be correct:

Dr Omlin concluded his presentation by stating that, “the development of this compound by AstraZeneca as a selective androgen receptor down-regulator in mCRPC has been terminated.”

Sometimes promising preclinical data just doesn’t hold up when it moves into human clinical trials. Another AstraZeneca drug with preclinical promise has gone to what Sally Church, PhD (@MaverickNY) refers to as “dog drug heaven.”

At the 2013 Annual Meeting of the American Society of Clinical Oncology in Chicago this past weekend, my impression of one of the most popular posters in terms of how fast the poster handouts disappeared (all 100 went in 7 minutes) was a phase 1 trial comparing PF-05280014, a potential biosimilar to trastuzumab (Herceptin) in healthy volunteers (ASCO 2013 Abstract No: 612)

Herceptin is used for the treatment of HER2+ breast cancer, and with global sales of over $5 billion, represents a major source of sales to Roche. However, Roche’s patent for Herceptin is expected to expire in 2014 in the UK, 2015 in Europe and 2019 in the United States, providing an opportunity for other companies to take a significant share of this market away from them.

Roche have long focused on life cycle management with strong patent defense built in to their long term strategic plans. In this case, their approach has been to launch new breast cancer products in the HER2 segment such as pertuzumab (Perjeta), for use in combination with Herceptin, and Kadycla (T-DM1) for advanced breast cancer patients who become treatment resistant to Herceptin. Trials are ongoing in the front-line setting with the goal of replacing Herceptin.

Several companies, including Amgen and Novartis, are looking to develop a biosimilar to Herceptin for the treatment of HER2+ breast cancer, and it now looks like Pfizer is in the race too. A biosimilar product is not a generic “copycat” i.e. a copy of a small molecule chemically synthesized to provide equivalent efficacy. Instead, a biosimilar is a copy of a biological compound such as an antibody or protein produced by living organisms intended to be equivalent to the original product. In general, monoclonal antibodies are much more difficult and complex to re-engineer than a pill or TKI.  This means that the main competitors in the biosimilar market are more likely to be generic offshoots of big Pharma rather than Indian generic companies, since they possess the technology and resources to engineer monoclonal antibodies.

There’s a lot of debate over biosimilars and whether they are truly identical. In the United States, the Biologics Price Competition and Innovation Act (BPCI) contained within the Affordable Care Act provided a regulatory route for biosimilars to be approved by the FDA, so long as they could be clinically shown to be “highly similar.”  Once approved, biosimilars are expected to be interchangeable, i.e. substituted for the original product with the expectation that lower drug prices will be the result. This represents a major competitive threat to Roche’s Herceptin HER2 franchise.

Interestingly at ASCO, Pfizer did not provide a QR code that linked to a PDF copy of their PF-05280014 poster, unlike most of their other posters at the meeting. I expect we will be hearing a lot more about biosimilars in the not too distant future, and the potential importance of this was highlighted by the intense popularity of Pfizer’s poster at the meeting.

Viewers of the ASCO 2013 preview video from Sally Church, PhD will have noted that PF-05280014 was one of her key breast cancer abstracts to watch out. If you haven’t already done so, here’s a link to the Pharma Strategy Blog ASCO 2013 Preview Video (free via sign-up) that is well worth watching.

Update June 5, 2013 5pm.  This post was not intended to be a comprehensive analysis of the biosimilar market and all the players (you have to pay me for that). However, Josh Berlin @BioPharmaJosh kindly pointed out on Twitter that the controversial Korean company Celltrion have filed for approval of their Herceptin biosimilar in Korea. This represents a competitive threat to Roche’s Asian market, and could give other companies a run for their money if they are first to market and file for approval elsewhere.

 

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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THE data of the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) that starts later this week in Chicago is expected to be the early clinical trial results for new breakthrough immunotherapies that target PD-1/PD-L1.

However, I’m also excited about the data being presented for the treatment of Chronic Lymphocytic Leukemia (CLL), a disease that kills 75,000 people a year around the world. ASCO typically does not have a strong focus on hematology and blood cancers, so it’s a reflection of the clinical significance of the data that it’s a hot topic at the meeting.

Several companies are in the race to bring promising new CLL drugs to market, and have presentations in Chicago.

Earlier this year, the FDA gave it’s new Breakthrough Designation to two CLL new products: ibrutinib, a bruton’s tyrosine kinase inhibitor from Pharmacyclics and obinutuzumab, an anti-CD20 monoclonal antibody from Roche Glycart. The breakthrough therapy designation recognizes the potential of these drugs to change the standard of care in CLL and meet unmet medical needs.

In many ways the changing CLL landscape reminds me of where prostate cancer was a few years ago just before new treatments such as enzalutamide and abiraterone came to market.

If you haven’t already done so I encourage you to watch the ASCO 2013 preview video from Sally Church (@MaverickNY) in which she highlights several of the key CLL oral presentations and posters. Update Sept 18: this video is now available on the Premium Content Video page.

A few of the CLL new products I’ll be looking out for at ASCO 2013 include:

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