Biotech Strategy Blog

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

Posts tagged ‘ibrutinib’

Potential of CAR T cell therapy in CLL

Standing from the crowd in refractory CLL?

Last year the two FDA approvals of tisagenlecleucel (Novartis) and axicabtagene ciloleucel (Kite/Gilead) CAR T cell therapy for hematologic malignancies such as pediatric acute lymphoblastic leukemia (pALL) and non-Hodgkins lymphoma (NHL) have captured a lot of attention.

It’s worth remembering, however, that back in 2010 the first patient who had a dramatic response to CD19 targeted CAR T cell therapy was actually a gentleman with advanced chronic lymphocytic leukemia (CLL), the case study of which was subsequently published by Porter et al., (2011) in the New England Journal of Medicine.

We’ve been following CAR T cell therapy and its potential in CLL for some time now, with all the successes, trials and tribulations along the way.

Dr David Porter (Penn) told BSB earlier this month:

“The very first patients we treated are now eight years out from their infusion, a little over eight years, and still in remission, still doing extremely well with no evidence of disease or progression, never had any other therapy. So, I think it’s become very clear that for some patients this is effective in the far advanced setting.”

It’s now two years since we last spoke and it was a great pleasure to reconnect with Dr Porter. As he told BSB at ASH in San Diego:

“One way you make it better is to understand why it’s working and why it’s not.”

What have we since learnt about the potential for adoptive cellular therapy in CLL and what new insights did we gain from new data presented at ASH18? The answers may well surprise you.

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ASH18 Highlights from Day 3

What latest ASH18 data jumps to our attention?

San Diego – It’s time to put another dozen studies in the spotlight and review what we can learn from the existing data with a view on where we’re headed in the future.

Today’s list covers a whole gamut of targeted therapies, bispecific antibodies, CAR-T cell therapies and other immunotherapies, what’s more we have a range of targets in the list too, and not the obvious ones either.

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ASH18 Highlights from Day 1

What a wet wet wet start to the annual meeting of the American Society of Hematology (ASH) meeting being held in San Diego – quite a change from the snow in Atlanta at last year’s event!

Either way, does it precipitate a windfall of excellent data?

A lull between the rain – a soggy day in San Diego

Here are some of our early highlights, which include updates on neoantigen vaccines, novel approaches with CAR T cell therapies, NK cell therapies, targeted therapies and more…

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The science behind the venetoclax clinical trial strategy

Buried amongst the intense hurly burly of a major medical meeting such as the American Society of Hematology (ASH) are the unsung preclinical researchers whose work largely makes clinical development possible. After all, few sensible companies would bet on an expensive clinical trial program, especially in combination, without first knowing whether such an approach is rational or not and has a decent shot of working efficaciously.

At stake here is the potential for building a blockbuster cancer drug niche by niche.

Venetoclax (BCL-2 inhibitor) got off to a somewhat slow start compared to say, ibrutinib (BTK inhibitor), which had a much broader initial indication and a lower risk of tumour lysis syndrome (TLS), yet it may actually have a wider application across multiple hematologic malignancies. This could well end up as one of those classic tortoise versus hare stories in the long run.

Back in 2013, we posted five interviews conducted with a range of experts including:

  • Dr Oliver Sartor (prostate cancer)
  • Dr Susan O’Brien (CLL)
  • Dr Deepak Sampath (BCL-2 and ABT-199)
  • Dr John Jenkins (then deputy director at the FDA)
  • Dr Renier Brentjens (CAR-T cell therapy)

To put this in context, consider that we just recorded 15 interviews at ASH this year alone!

As regular readers know, we like to follow people and R&D stories over time, so while in Atlanta at ASH17 we took the opportunity to move a particular story forward – we wanted to learn where Dr Sampath and his colleagues are now and also where they are headed next. This gives readers a head start on anticipating what future clinical developments might be mentioned at JPM18 by either Genentech/Roche or AbbVie.

In our latest expert interview, we pick up and continue the discussion with Deepak Sampath to find out what’s happening with venetoclax four years on… it turns out quite a lot and makes for very interesting reading indeed.

Dr Deepak Sampath (Genentech)

Curious to now more about what this scientist and his work in BCL-2 targeting is all about?  Check out this short excerpt:

 

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ASH17 masterclass with Dr John Leonard on lymphomas

In our latest thought leader interview from the annual meeting of the American Society of Hematology (ASH) Dr John Leonard (Weill Cornell) provides a lesson on how to interpret key lymphoma data such as ECHELON–1, CAR T cells, and other topics at ASH, as well as what he’d like to see more of in lymphoma clinical trials.

In this hard-hitting interview, Dr Leonard reminds us that the media should not be a mere extension of the PR of companies. Instead he offers his real world insights into what may or may not be practice changing, and how we should interpret CAR T cell therapy data.

Dr John Leonard (Weill Cornell)

It’s a must read for anyone with an interest in lymphoma… here’s an excerpt to give you a flavour of the wide ranging discussion:

 

 

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ASH17 Will MURANO impact the CLL landscape?

As we continue rolling out our ASH coverage, we now move on to the in-depth analyses and thought leader interviews post meeting… What do experts really think about the critical questions that arise from new data? What is practice changing versus a nice to have in a small subset of people?

Someone said to me recently, “You seem very picky about who you interview. Why’s that?”

You betcha we are!

ASH17 in Atlanta

There are hem/oncs, thought leaders, and true experts whose opinions we value and know are solid and fair balanced in their commentary. There are also others who have major COI and will say whatever needs to be said about a particular individual study they are involved in, but are not reliable in a strategic perspective of the broader landscape or the impact of a study in terms of future trends.

I’d rather talk to people in the first category and learn from them – they don’t have to know everything or even agree with our own viewpoint, but they do need to be independent and fair balanced.

In the first of our ASH interview series, we posed some tough questions to a CLL expert and here’s a snippet on what he had to say:

Hah, at least we are thinking along the same lines!

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Commentary on ASH17 Day 2 in Atlanta

Snow at GWCCAtlanta – it’s day 2 of the annual meeting of the American Society of Hematology (ASH) meeting here in a chilly and snowy Atlanta.

I have to confess snow is not something we normally associate with southern States such as Georgia, but a cold snap has taken it’s toll on the ASH meeting, with many presentations cancelled as a result of travel delays.

Sunday at ASH is well known for the plenary session that takes place in the afternoon, but what else is hot at the meeting today? We’ve been talking to thought leaders, spending time in the vast poster hall and hearing some oral abstracts. There’s been been a surprising amount going on today at ASH in Atlanta.

If you are at ASH then you’ll know that all the sessions end at the same time, resulting in a massive movement of people as they go to the next session, as we saw today:

 

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Top 10 #ASH17 abstracts to watch out for

No ASH pre-conference coverage would be the same without a shout out to Dr John Leonard (Weill Cornell). For 10 days prior to the annual meeting he counts down each day with a lymphoma study that caught his attention and tags it #LeonardList. The first one went up yesterday:

Do follow Dr Leonard and his lymphoma selections on Twitter – there are usually surprising ones in the middle that are quirky or interesting that makes you stop and think more carefully.

Our #ASH17 series we have already covered aggressive lymphomas and also developmental therapeutics.

Atlantic Olympic Sculpture

Up next in our third ASH17 Preview, we take a broad look at the wealth of abstracts available and highlight ten key presentations, irrespective of tumour type, which readers should be watching out for.

Some of these ‘Champions’ may not be immediately obvious and include interesting preclinical findings, intriguing new products in development, as well as eagerly awaited mature data from recently approved therapies. It’s an eclectic mix, to be sure.

There are definitely some early trends and interesting new molecules emerging from company R&D pipelines that are worthy of further consideration in this year’s batch of abstracts.

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ASCO 2017 CAR T Cell Therapy Preview

Chicago RiverAlthough ASH and ASGCT are important meetings for CAR T cell therapies, there are still some intriguing data to be had at ASCO next month, including both oral and poster abstracts.

In our latest ASCO 2017 Preview, we take a look at what to expect from in the CAR T cell space.

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Promising new agents to watch out for in Chronic Lymphocytic Leukemia

Over the last five years the face of the chronic lymphocytic leukemia (CLL) landscape has changed quite dramatically with the advent of new approvals in several categories. These include anti-CD20 antibodies, BTK inhibitors, PI3K inhibitors and apoptotic Bcl–2 inhibitors.

In yesterday’s wide ranging interview we explored in-depth how these therapies are impacting the broader landscape, as well as emerging trends in how these regimens might be used.

In Part 2 of the ongoing series, we spoke with another CLL expert and explored promising new and earlier agents in development for a different perspective on how outcomes might be improved further.

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