Biotech Strategy Blog

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

Head and Neck cancer – or to be more precise – squamous cell carcinoma of the head and neck (SCCHN) has joined the checkpoint inhibitor club with two FDA approvals this year. National Harbor Maryland

Firstly, we saw the accelerated approval of pembrolizumab (Merck) based on objective response rate on August 5, 2016 for patients with recurrent or metastatic head and neck squamous cell carcinoma (SCCHN) that has continued to progress despite standard-of-care treatment with chemotherapy.

It’s a dismal disease with a generally poor prognosis in advanced patients once initial therapy fails.

While some patients do benefit with anti-PD–1 checkpoint therapy, the overall response rate in the KEYNOTE–012 trial of 174 patients was pretty low, i.e. 16%. In other words, the majority of patients do not respond or receive any clinical benefit.

Secondly, last week on November 10 nivolumab (BMS) was approved by the FDA based on the phase 3 CheckMate–141 data presented at ASCO earlier this year. The data was published in the New England Journal of Medicine to coincide with the FDA approval.

There were no statistically significant differences between the two arms for median PFS (2.0 months with nivolumab versus 2.3 months with standard therapy, HR for disease progression or death, 0.89; P=0.32) or ORR (13.3% vs. 5.8%) for nivolumab versus investigator’s choice, respectively. There was, however, a clear benefit in favour of nivolumab in median overall survival (7.5 months in the nivolumab group versus 5.1 months in the control group; HR 0.70; P=0.01).

This effect on patient outcome is a classic pattern for cancer immunotherapy with checkpoint blockade. Response rate and PFS are measurements that are very relevant to chemotherapy, but they are not as relevant to cancer immunotherapies where what is impacted more noticeably is overall survival and the long tail of the curve.

With two approved anti-PD–1 monotherapies in SCCHN, the next challenge has now become how can we improve on monotherapy by boosting the number of PRs to CRs potentially improving long term outcomes and/or turn non-responders into responders? This is the stage we are at in many tumour types now.

Combination approaches are believed to be the way forward, which is why we anticipated with great interest the lirilumab plus nivolumab head & neck combination data presented this past weekend at the 2016 Society for Immunotherapy of Cancer (SITC) meeting at National Harbor, MD. The presentation is available for download on the Innate Pharma website. The data raises numerous questions and scenarios that can be considered…

  • Are the data exciting, encouraging or disappointing?
  • Are the results enough to give confidence if a phase 3 trial with the combination were to follow?
To address these questions and other critical issues – including red and green flags – we took a deep dive into the data in the context of scientific facts and explored the landscape carefully.

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Post 2016 US Election, we move on and get back to business with an in-depth review of some new science and clinical data.

ash-2015Yes, it’s time for another Bushidō – “Way of the Warrior” – guide to the key ASH abstracts!

Here we focus on acute myeloid leukemia (AML), a difficult and challenging disease to treat with a high unmet medical need for new effective therapies.

In this Preview we look at key companies in the AML space, as well as a look at what’s happening in classic targets and also some new ones that are receiving notable attention, both preclinically and also in the clinic.

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It was only five years ago that the number of abstracts on CAR T cell therapies at the American Society of Hematology (ASH) ran to a dozen or less. Fast forward to 2016 and we now have tens of them, almost too many to count, let along review quickly and easily.

ash-annual-meeting

A scene from ASH 2015…

To give you an idea of the staggering speed of progress, in 2010 it took me less than half an hour to search and read all the CAR T cell abstracts, now it takes nearly a whole day to peruse and review them carefully.

We can’t resist a challenge…

As usual, we will write in more depth from the meeting as the data emerges in real time since many of the abstracts are often placeholders with updated information provided at the conference itself.

For now, here we provide an in-depth preview of the CAR T cell landscape in terms of the players, the products, new scientific research, biomarkers, emerging trends and more in a handy What to Watch For (W2W4) guide on key areas to expect at ASH to enable better enjoyment and awareness as the data rolls out next month.

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The abstracts (apart from the late-breakers) for the 2016 annual meeting of the American Society of Hematology (Twitter #ASH16) went live at 9am ET today. Link to 2016 ASH Abstracts.

ASH16 takes place in San Diego from December 3-6.

View of San Diego from ASH 2011In this initial post, I’m sharing my first impressions of what may be some hotly contested trials at ASH16 in San Diego, as well as a few intriguing abstracts with combination data that caught my attention.

With over 3,000 oral and poster presentations, all typically of a high quality, this by post by definition, is a highly subjective one.

After we’ve had more time to process the data, further ASH16 Previews will roll out over the next few weeks highlighting more key abstracts to watch out for by tumour type or treatment modality.

In-depth commentary and analysis will follow after we’ve heard or seen the data presented at the meeting.

I’ll be flying to ASH from the EORTC-NCI-AACR Molecular Targets meeting. Do say “hello” if you have plans to be in Munich or San Diego.

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Part 3 of our series on Gems from the Poster Halls at ESMO continues with a look at another four important combination studies that may be of keen interest to readers.

These include both targeted therapies as well as immunotherapies.

Some of the posters I was originally keen to write about turned out a little unexpectedly with some issues to address i.e. lack of efficacy or unwanted toxicities based on the dosing schedule used and may require tweaking of the dosing, schedule or trial design. Others will unfortunately be destined for dog drug heaven unless a new tumour type offers more promise. Such is the R&D roller coaster that is oncology – sometimes we forget that more compounds fail than make it market.

The good news is that there were plenty of promising approaches that are worthy of writing up and discussing. In the third part of our poster mini-series, we take another deeper dive with a careful look at some new data in Copenhagen.

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One of our popular series from conferences is Gems from the Poster Halls, where we take a look at some of the studies or research data that caught our attention and explain how they may have future significance. In the past, posters have lead to phase 2 or 3 trial designs and subsequent approval. Others have sadly missed signals in small studies that could have prevented an expensive phase 3 faiure. Hence, it is often important to pay attention to posters.

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The ESMO16 Poster Hall Maze

Posters can also give early warning for what’s developing in pipelines. The BTK inhibitor, ibrutinib, was originally codenamed CRA–032765 (at Celera) and later PCI–32765 (at Pharmacyclics), for example, while the PI3K-delta inhibitor, idelalisib started life as CAL–101 (at Calistoga). We previously followed the progress of these compounds while they were in preclinical and phase 1 and documented progress long before they became active drugs in a race to market in CLL.

My favourite codename is always going to be STI–571 (imatinib). We would start planning ASCO and ASH activities every January and September, so companies should be well in hand in their preparations for ASH and SABCS by now. There’s a tremendous amount of work involved behind the scenes in order to have a great event, and I’m not talking about the fripperies like exhibits and light boxes here.

Last year at ECCO, StemCentRx burst on the scene and were subsequently acquired at a significant premium by AbbVie, taking quite a few people by surprise.

So what can we learn about the data from ESMO this year? What new trends are emerging this time around?

Here, we take a fresh look at FOUR interesting new developments from small and large pharma/biotech companies alike in Part 2 of the Gems series. In the first one [Link], we interviewed an expert and discussed their approach to biomarkers in early small studies to help them better design larger follow-on trials more effectively.

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On their blog earlier this month, the Broad Institute posted a nice piece wittily entitled, “Opinionome: What will be the next big –ome?

It included a chart exploring the main -omes and -omics, as well as suggestions from experts on what they saw as the next hot thing in this space.

university-of-copenhagenAn interesting thing that stood out to me in this timely piece was the complete and utter absence of the glycome and glycomics, which would be my answer to their provocative question – maybe not necessarily as the most hyped one  – but certainly as a very impactful one.

While in Copenhagen for ESMO, we took some time out to meet with a leading global expert in the obscure field of glycomics and had the pleasure of hearing what he had to say about this exciting field of research.

The research may impact not only our knowledge about how cancer progresses, but also how it can be used to design and devise better therapeutics, including CAR T cell therapies. The answers we heard may therefore surprise.

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esmo-poster-hallThis post started out as a look a one of the Gems from the Poster Halls at ESMO, including an interview with a thought leader in biomarkers, then morphed into a broader Op Ed that includes a strategic analysis of where we are, where we are going, and how we could get there more effectively and efficiently.

It’s time to turn tables to start challenging the status quo and slow pace of development if we really want to make a difference in advanced ovarian cancer.  I was recently challenged by a well respected GYN oncologist to delineate how we could do things differently so here are some ideas, along with the scientific rationale in my response to his gauntlet.

Is the ideal situation one where multiple companies randomly throw mud at the wall hoping something sticks the best approach? Or are there more effective ways to make a difference?

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One of the surprising things I learned over the summer was how many people misunderstand how advanced ovarian cancer is treated as a disease… it isn’t really one disease to start with, but is actually a series of subsets depending on the molecular underpinnings and also how women with the condition react to therapy.

Imagine then, when we see a series of press releases and abstracts emerge on PARP inhibitors followed by a rather indecent and sudden rush to judgment by Wall St and investors on the ‘Winner takes All’ out of the lot?

Except that real life doesn’t work that way in clinical practice.

A head/desk moment to be sure, and a frustrating one for those who understand what this is actually all about. To address this siituation, we had the pleasure of communicating with KOLs remotely or sitting down with several thought leaders in gynecologic cancer in Copenhagen to debate various aspects relating to current treatment paradigms, new clinical trial data with PARPs, and what they are most excited about going forward.

Copenhagen Waterfront

Copenhagen Waterfront

Today’s post highlights our latest thought leader interview with an experienced GYN oncologist and their perspectives on the rucaparib and niraparib data presented earlier this month at ESMO.

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One of the surprise controversies at ESMO16 was the fall-out between Myriad Genetics (NASDAQ: MYGN) and Tesaro (NASDAQ: TSRO) over whether the company’s PARP inhibitor, niraparib, should require a companion diagnostic for the treatment of women with platinum-sensitive ovarian cancer in the maintenance setting. We previously wrote about this from Copenhagen (Link).

christianhavn

Christianhavn

Tesaro were so keen on controlling their message, in the run-up to ESMO, they even went to the trouble of taking out a legal injunction against Myriad Genetics in an attempt to prevent them publishing their own press release discussing the niraparib data.

We knew about this “off the record” at ESMO, but it’s now a matter of public knowledge and John Carroll admirably reported the story on Endpoints last week (Link).

It is a sad reflection on any biotech partnership or pharma alliance if you can’t reach an agreement in private, and have to resort to an injunction in US Federal Court. Doubly unfortunate when you lose the injunction too!

As many readers are already aware, back in June 2014 AstraZeneca failed to convince an FDA ODAC about the merits of olaparib in the same indication that Tesaro are seeking. This is why the data for Tesaro and their regulatory/commercial approach justifies careful scrutiny.

What’s more, data from Myriad Genetics was key to AstraZeneca obtaining a subsequent indication for olaparib in more advanced ovarian cancer, so their experience in this space cannot be dismissed.

dr-johnathan-lancaster

Johnathan M. Lancaster MD PhD

At ESMO, the Myriad Genetics Laboratory Chief Medical Officer, Dr Johnathan Lancaster kindly spoke to BSB.

He shared his perspective on the niraparib data and why a companion diagnostic should be considered based on the NOVA trial data presented by Dr Mansoor Mirza. You can read more about the data in The NEJM paper that was published simultaneously (Link).

Dr Lancaster was formerly Director of the Center for Women’s Oncology, and Chair of the Department of Women’s Oncology at Moffitt Cancer Center in Tampa.

While he does bring a corporate bias based on his position at Myriad Genetics Laboratories – and Myriad clearly have a vested interest in selling diagnostic tests – his clinical perspective is worthy of consideration and it’s one that is shared by other GYN oncology thought leaders we have spoken to (see: earlier post, “what Tesaro aren’t telling you about niraparib”).

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