Biotech Strategy Blog

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

Posts tagged ‘Juno’

San Diego – Monday at the 2016 Annual Meeting of the American Society of Hematology (#ASH16) is typically a day of multiple oral sessions in parallel.

This year it was a major challenge doing a mad dash between sessions as the meeting is now so big that in San Diego it’s being held, not only at the vast convention center, but is also using the meeting rooms of three nearby three hotels – it’s literally a mile walk to go from one end of the convention to the other, so you have to factor that time into your crazed schedule with multiple clashes.

On the positive side, there’s even courtesy pedicabs – cycle rickshaws (great idea & fun) – I caught one at 7am the other day to save my toes from at least one #blisterwalk…

Pedicab at ASH16 in San Diego

Following on from our ASH Highlights 2016 Part 1, this post answers critical BSB Reader questions that have come in thick and fast and require more than 140 characters on Twitter to answer.

Predictably, the majority of the first tranche of questions have been CAR T cell therapy related, so if you have a keen interest in this area, this is the post for you.  We tackle 5 critical questions and offer some insights.

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San Diego – after “Flying Friday” where I flew from Munich to San Diego, Biotech Strategy Blog coverage of the 2016 annual meeting of the American Society of Hematology (ASH) is now done for another year.

Downtown San Diego during ASH 2016 With over 27,000 attendees – it’s the largest ASH annual meeting I’ve seen in 20 years of coming here!  ASH is definitely the pre-eminent global meeting for hematology and blood cancers.

As you might expect, the thought leaders at this event are super-busy, but we’ve already managed to catch up with a few, and we’ll be rolling out interviews in the “post-game show.”

Subscribers have been asking what’s really hot at ASH this weekend, so reflecting my interests and the sessions I went to, here are my seven highlights/learnings of ASH 2016 (so far). There’s a lot more data to come!

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Juno Therapeutics LogoThis is an important and necessary follow-up to the ongoing Juno JCAR015 story in July after three patients had died due to complications associated with cerebral oedema. At that time, the company attributed the deaths to the inclusion of fludarabine in the lymphodepletion given prior to CAR T cell therapy infusion, leading to severe neurotoxicity, and clinical hold was lifted by FDA after the protocol was subsequently amended.

This morning came the dramatic announcement that following the protocol amendment, Juno has voluntarily placed the ROCKET trial on clinical hold again following another two deaths from cerebral oedema.

What gives and what are the consequences here?

We take a joint look at some of the issues that arise from this situation in terms of the CAR T cell therapy market and also pen thoughts from the analyst call this morning.

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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 race to the be first to market in the United States with a CD19 directed CAR-T cell therapy is a bit like the America’s Cup Challenge Race Series – one boat/company is ahead and then another is ahead, it’s an ever changing and fluid situation…

Americas Cup Portsmouth

In this post, we’re looking at questions from subscribers – so what’s in the July BSB mailbag?

* CAR T Cell Therapy: Is the recent FDA hold – that came and went in record time, a setback to Juno? Who will win the CAR-T race to market in the United States? What is the market opportunity in Europe?
* Jounce/Celgene Deal: Celgene have a reputation for doing deals with innovative biotech companies, but then what? Is the Jounce deal a good one, or is it a value destroyer?

There are a few other questions in the mail bag, but the above gives you a flavour of some of the commentary in this post.

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No CyclingLate this afternoon, Juno Therapeutics ($JUNO) announced (link to press release) that the FDA had put a clinical hold on enrollment into a phase 2 trial of their JCAR015 construct in relapsed refractory acute lymphoblastic leukaemia (ALL) in adults in the ROCKET Trial: NCT02535364.

The decision by the FDA was as a result of three recent patient deaths reported to be due to neurotoxicity. In after-hours trading the stock dropped 30% from a market close of $40.82, reaching an after hours low at time of writing of $26.66 at 4.43pm ET.

In this post we look at what happened, the possible reasons behind it, and what it may mean for other CAR T companies. A leading CAR-T cell expert also provided BSB with some commentary after the news broke.

Good News: Post now updated following FDA lifting hold on ROCKET trial.

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Yesterday, Juno Therapeutics and Celgene announced a ten year collaboration that is expected to close in July-August.  In short, Celgene has exclusive right to entire the Juno portfolio in oncology and auto-immune cell therapy products in development outside North America and co-promote certain programs globally (not specified).  Juno, meanwhile, gains the option to co-develop and co-promote select Celgene programs (also not specified).

You can see the terms of the deal here.

And listen to the webcast from the call after hours.

This news comes hot on the foot of an earlier announcement that the FDA accepted the Juno IND for JCAR017, a CD19 CAR T cell therapy being developed in relapsed/refractory NHL scheduled to initiate in 2015, with the possibility of a registration trial commencing in 2016.

What was fascinating, however, was the BioTwitter reactions last night – predictably, people either loved or hated the news – it clearly came as a surprise to many.

This morning my inbox is full of questions on this dramatic topic from subscribers, so here are some topline thoughts on this issue to answer the questions coming in.

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“Nothing lasts forever, because nothing ever has.”

James Shelley, The Caesura Letters

This year’s annual AACR meeting was so good, we could probably write another 50 posts and still not be done! With ASCO fast approaching, however, it’s almost time to draw it to a close and the final post conference note will be published on Monday.

Today is the penultimate report and focuses on the key highlights that caught my attention in immuno-oncology, which covers the gamut from checkpoint inhibitors, co-stimulants, innate immunotherapy and CAR T cell therapy to bispecific antibody TCRs.

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This weekend, a controversy erupted at the American Association for Cancer Research (AACR) relating to Juno’s chimeric antigen receptor (CAR) T cell therapy following a series of tweets by Jonah Lomu, a keen biotech investor:

This innocuous looking tweet started a maelstrom of speculation and wild rumours that spiraled a little out of control.  This was perhaps not helped by Dr Michel Sandelin being a little caught off guard after his presentation yesterday, essentially saying, ‘no comment’ and that the trials were stopped for ‘safety reasons’.  Rather than calm things down, it unfortunately added fuel to the fire.

renier-brentjensYesterday, we spoke remotely with Dr Renier Brentjens (MSKCC) off the record and ascertained that the furore, far from being a major incident that impacts the whole field negatively, was actually a tempest in a tea cup that has been blown out of all proportion.

After his invited presentation and Dr June’s discussion in the clinical trials symposium today, Dr Brentjens agreed to answer our questions on the record to provide some detail and straight facts to put things in context to address the concerns.

To learn what Dr Brentjens had to say in this exclusive interview, check out the full post – it makes for interesting reading:

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Without much further ado, you can hear what Dr Brentjens has to say about the ‘safety concerns,’ interactions with the FDA and the CAR T cell therapy class effects in the brief, unedited, yet very candid interview below.

Please note that I’m here at the conference centre without a laptop or editing to tone down the background hubbub – this is the raw recording, which is just how I heard it live:

Some thoughts:

The two adult ALL deaths reported are unfortunate but should come as no surprise when considering these patients were mostly considered ‘salvage’ and very sick indeed.  I think MSKCC and the FDA are rightly taking a sensible and cautious approach to patient safety while they consider the need for dose reductions before resuming the trials once IRB approval has been obtained.  While the deaths were seen in the adult ALL study, the institution took a conservative approach and temporarily suspended all of the studies in that protocol group. I thought this was a measured response.

Tumour lysis syndrome and cytokine release syndrome are both, in some ways, a sign of great efficacy, as we have clearly seen with AbbVie’s Bcl2 inhibitor, ABT-199 in the past.  The challenge with highly effective therapies, as always, is going to be learning how to expand the T cell production and induce tumour cell killing in a controlled way.  Not every patient is going to be able to cope with the dramatic biologic effects that ensue, nor is the response consistent in every patient.  Controlling the immune system response is not an easy task.

Interestingly, the neurotoxicity issues associated with confusion etc were also reported by Dr Kochenderfer in the Kite lymphoma trial at ASH, so it is unclear whether this is a class or dosing effect. It clearly isn’t limited to just the Juno therapy. No doubt this will be continue to be watched and monitored carefully once trials resume at a lower dose. We should remember that these are patients not only with poor performance status, but also with a very poor prognosis so the risk:benefit considerations are very different from a frontline trial in healthier patients.

Dr June brought up the issue of persistency and implied that the MSK/Juno construct had an effect for only a few weeks, while the UPenn therapy was longer (months).  This was not my perception from all the data I saw recently at ASH and Dr Brentjens was quick to address this in the interview above.

My expectation is that a dose reduction will be quickly proposed, the exclusion criteria amended for co-morbidities and a revised IRB approved to all parties satisfaction, including the FDA.

We can expect more data on CAR T cell therapy at ASCO, where we will continue to follow the progress of this exciting class of immunotherapy.  We should not expect it all to be plain sailing, there are bound to be a few periods of doldrums (challenges to be overcome) interspersed between the exhilarating and positive data that is being reported in very refractory and sick patients.

{UPDATE – April 19th, 2014}

We’ve literally just heard from Juno that the adult ALL study hold has now been lifted by the FDA and they are enrolling patients again.

This is really excellent news for patients and good work all around in getting the issue resolved so promptly, which is no mean feat.

Juno have confirmed that the clinical trials database has yet to be updated administratively (that will probably happen early next week after the Easter holiday weekend), but all five trials associated with the IND have had their hold removed and are recruiting.

 

 

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