Biotech Strategy Blog

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

Posts tagged ‘Acute Myeloid Leukemia’

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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It’s been quite a roller coaster week so far for CAR T cell therapies, with Gilead announcing its intended acquisition of Kite Pharma on Monday.  If that wasn’t enough, Wednesday brought another surprise – the FDA approved a rare double header – for Novartis’s CTL019, now known as tisagenlecleucel (Kymriah) for pediatric and young adult patients with a form of acute lymphoblastic leukemia (ALL), as well as a new indication for Genentech’s tocilizumab (Actemra) for the treatment of CAR T cell-induced severe or life-threatening cytokine release syndrome (CRS) in patients two years of age and older.

Inevitably there has been much hullabaloo and much anticipation over the expected price tag that might accompany the first cell therapy product approved in the US. Whatever your view on this, many of us were no doubt relieved it came in under $500K ($475K, with no charge for the product in the first month if there was a manufacturing failure or no response).  While undoubtedly pricey, frankly it could have been a lot worse given the relatively small patient population.

Of course, the approved therapy isn’t the only expected high ticket item – there’s also hospital costs (including highly trained physicians and nurses), ICU costs (for very sick patients), supportive care costs (including tocilizumab if CRS occurs), not to mention any lab, diagnostic or monitoring tests required. All of these will no doubt push the total bill nearer to $1M.  In children though, the lifetime value of curative intent and many additional years of life is a much easier to grasp concept for payers than adding a few extra months at a high cost in adults.

These issues do raise the stakes for Kite and what they plan to do strategically in aggressive lymphomas, where there is a larger pool of eligible people for therapy, which must be offset by lower response rates (vs. pALL) and likely lower durability based on the data we’ve seen to date.  If we are truly moving into a world of value based pricing in the US, then efficacy and tolerability will ultimately have an impact on the perceived cost and value of treatment.

As Warren Buffett, the famous value investor has been want to say, “Price is what you pay, value is what you get.”

Whoa that’s a lot to think about – who knows what Friday may bring at this rate – and we still have the Kite Axi-Cel approval in aggressive lymphomas to go yet…

Meanwhile, there’s also a high unmet medical need for new effective treatment options in Acute Myeloid Leukemia (AML), especially in the relapsed/refractory setting, which is why we’re firm supporters of the Beat AML trial that the Leukemia and Lymphoma Society are pioneering. (See: Interview with Dr Brian Druker).

There’s also interest from several companies in a variety of novel targets, including CD123.

Notre Dame, Paris

Cellectis recently announced the enrollment of the first AML patient into their trial of an allogeneic CAR T cell therapy (UCART123) targeting CD123.

Quite aside from the issue of addressing whether such a product can be administered safely and effectively, one major why there is notable interest in Cellectis is because an allogeneic CAR T cell therapy offers the potential of a much cheaper off-the-shelf product as well as enhanced performance from an abundance of fit immune cells from healthy donors rather than tired or exhausted ones from people who are sick, thereby reducing the risk of manufacturing failure.

While in Paris, I spoke with Cellectis Chief Medical Officer, Loan Hoang-Sayag, MD about the trial design and CD123 as a target in AML.

This is the third and final post in our summer mini-series on gene editing and allogeneic CAR T cell therapy.

The first in the series featured an interview with Professor Waseem Qasim (Link), and the second with Cellectis CSO, Dr Philippe Duchateau (Link).

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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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Acute Myeloid Leukemia (AML) is challenging disease to treat and quite distinctly different from its cousin, acute lymphoblastic leukemia (ALL).  The first is more common in adults, while the second is more prevalent in children.  Success rates with pediatric ALL have far outstripped what we have achieved with adults in AML to date, partly due to the elderly nature of the disease making for poorer outcomes with stem cell transplants (SCT), as well as increased clonal heterogeneity and cytogenetic complexity with age.

Quite a few FLT3 inhibitors have come and gone over the years – many keen observers will remember Cephalon’s (now Teva) TKI called CEP-701, which was tested in relapsed/refractory disease and Elderly AML, for example, and slid off largely unnoticed to dog drug heaven.

How much does clinical trial design impact a drug’s success or failure?

Sometimes quite a bit, as this story with midostaurin demonstrates; limited activity in advanced disease but much more dramatic results in the upfront setting.  Clearly, sometimes testing drugs in later disease does not predict their future performance elsewhere!

To put more colour on the data presented at ASH, we interviewed a thought leader in adult AML for his perspective on the FLT3 R&D developments.

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San Francisco F line Trolley originally from MilanSan Francisco – Acute Myeloid Leukemia (AML) is largely a disease of the elderly since it is uncommon before the age of 45. It generally has a much poorer prognosis compared to other leukemias such as CML and even ALL.

There are two main treatment options – high chemotherapy (ara-C is the main bedrock) or a stem cell transplant in those patients who are considered eligible. With the average age at diagnosis being ~66yo, many patients may be elderly and frail, making a SCT not a viable option.

Ara-C (cytarabine) has been around for many years and despite numerous clinical trials, it has yet to be displaced. There’s plenty of room for improvement though, and a high unmet medical need still exists. The good news is that despite the challenge of finding a highly effective yet well tolerated therapy, there’s a lot of R&D activity in this space.

In this preview of the data to be presented at the American Society of Hematology (ASH) annual meeting in San Francisco, I highlight my top 10 AML abstracts that are worth checking out.

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