A couple of years ago we had a lot of fun here on BSB following the progress of ibrutinib (Imbruvica), obinutuzumab (Gazyva), and idelalisib (Zydelig) in CLL and indolent NHL. It seemed back then that the stunning trio were the hot topics for some time at ASCO and ASH meetings. Exciting times! All three target different entities (BTK, anti-CD20 and PI3K-delta) and made it past the tape to market, with Gazyva leading, Imbruvica a close second and Zydelig a slightly more distant third. I was reminded of the race again over the last week or so as the 4Q earnings were announced, with Pharmacyclics reporting almost $500M for Imbruvica last year and estimating sales to hit $1B in 2015. In contrast, Zydelig revenues for 2014 were $23M, reflective of their much later market entry in the US.
Still, that was a pretty impressive set of drugs all in development at the same time.
Two other agents we also reported on regularly were Infinity’s IPI-145, a PI3K delta-gamma inhibitor, and ABT-199/GDC-0199 (now known as venetoclax). I haven’t heard much about the former of late, but after a few missteps, the next big question to consider is whether venetoclax is coming back strongly or destined for dog drug heaven?
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One of the things I most enjoy in cancer research is hearing wonderful patient stories from oncologists who are at the coal face of clinical trials. They get to deal with death and dying every day and like those in Pharma R&D, also live for the successes, the drugs that make it through pipeline despite great odds against them and make a meaningful impact on the daily lives of ordinary people.
We’ve all heard topline data presented at medical conferences around the world, but what the summary data can’t tell you is how a drug can impact people in ways that are clinically meaningful yet are more obtuse to capture in the aggregate. This is why case studies at CME sessions are increasingly popular, because they add value and context to common issues in a way that a Kaplan-Meier curve can never do.
With the flurry of recent US and EU approvals for obinutuzumab (Gazyva), ibrutinib (Imbruvica) and the newest kid on the block, idelalisib (Zydelig), in CLL and indolent lymphomas, I wanted to take a look at these drugs from a different perspective.
A reader wrote in asking which of these new agents would emerge the winner and why?
Today’s post therefore offers some thoughts on the emerging CLL landscape now that we are shifting from new product development to the marketplace.
Drugs mentioned: Gazyva, Imbruvica, Zydelig, ABT–199/GDC–0199, Arzerra, IPI–145, CTL–019
Companies: Roche/Genentech, J&J/Pharmacyclics, Gilead, GSK, Infinity, Novartis
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Previously, we discussed the role of new agents being developed for aggressive non-Hodgkins lymphoma (NHL) with Dr Nancy Valente of Genentech, particularly how their antibody drug conjugates (ADCs) could have a potential role to play in revolutionizing treatment for patients with an otherwise poor prognosis.
The second half of the interview from ASCO 2014 focuses on more indolent disease, namely chronic lymphocytic leukemia (CLL) and the role of their novel therapeutics obinutuzumab (Gazyva) and ABT–199/GDC–0199.
We’ve heard a lot of positive data about the anti-CD20 monoclonal antibody, obinutuzumab, but the Bcl2 inhibitor undergoing co-development with AbbVie has had a bit of a chequered history to date. There is no doubt that ABT–199/GDC-0199 is highly potent, while lacking the severe myelosuppressive effects (thrombocytopenia) of its predecessor, navitoclax — which can be both a blessing and a curse — as the phase I single agent investigators discovered recently when severe tumour lysis lead to two sudden patient deaths.
It is important to address these issues expeditiously in a safe and rational way to ensure patient safety for those who enroll in both current and future trials. This is a critical issue we discussed at length with Dr Valente and how the company has been handling it.
At the AACR Molecular Targets meeting last November, many readers will remember that we learned about Genentech’s research plans for combinations with GDC–0199 in CLL and NHL in an interview with one of the scientists for that program, Dr Deepak Sampath.
Today, it’s time to look at where and how this exciting agent might impact CLL. Obviously, both CLL and NHL have commonalties and overlap, since they are both B cell disorders, so often what works in one disease often works well in the other too, as rituximab has clearly demonstrated.
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Now that the last of the 2013 cancer conference season is finally over, we’re going to run a couple of post meeting summaries this week from ASH as a few subscribers have asked for the Cliff Notes version of what was hot – or not in the context of the market.
New treatments for Chronic Lymphocytic Leukemia (CLL) was one of the hot topics at the recent annual meeting of the American Society of Hematology in New Orleans.
Hot on the heels of Roche’s recent FDA approval for Gazyva (obinutuzumab/GA101) in CLL, other companies in the race to market including:
- Pharmacyclics and Johnson & Johnson (ibrutinib)
- Gilead (idelalisib, GS-9973)
- Infinity (IPI-145)
- AbbVie and Roche (ABT-199/GDC-0199)
- Novartis (CTL019).
Here’s my subjective and personal assessment of the winners and losers based on the data presented:
Originally, I was thinking of doing an in-depth review of lymphomas i.e. non-Hodgkin’s lymphoma (NHL), which involve 85% of lymphomas and Hodgkin’s lymphoma (HL), which take up the remaining 15%. This topic, however, has been largely done to death already.
There are are some very useful sources of carefully curated content that I enjoy following every year and in this post I’m going to direct you to some of those and highlight where I think the critical topics are in lymphomas.
Companies mentioned: Roche, GSK, AbbVie, Pharmacyclics, Gilead, Infinity, Seattle Genetics
Drugs mentioned: Rituxan, Arzerra, Gazyva, ABT-199, ibrutinib, idelalisib, IPI-145, Adcetris
The chronic lymphocytic leukemia (CLL) landscape has been one of the most dynamic and exciting over the last 12 months, with many new therapies emerging against different targets from CD20 to BCR signaling, Bcl2 to the PI3K pathway. Other new targets may also soon emerge.
The annual meeting of the American Society of Hematology (ASH) in New Orleans sets the scene for the rollout of more mature data and affords an early evaluation of where the various companies competing in this space may shake out. Given that we are moving beyond traditional chemoimmunotherapy to evaluate several newer classes of therapy including B cell receptor (BCR) and PI3K signaling, anti-CD20 antibodies, anti-CD19 chimeric antigen receptor T cell technology (CART) it looks to be shaking out to an exciting conference.
Companies mentioned: Roche/Genentech, Gilead, Pharmacyclics, Abbott, Celgene, Infinity, Incyte, ONO, Amgen, TG Therapeutics, Novartis
Products discussed: rituximab, bendamustine, obinutuzumab, idelalisib, ibrutinib, ABT-199, CC-292, GS-9973, IPI-145, ONO-4059, INCB40093, AMG 319, TGR-1202, CTL-019
The Food and Drug Administration (FDA) today approved Roche/Genentech’s obinutuzumab (Gazyva), also known as GA101, for untreated Chronic Lymphocytic Leukemia (CLL) in combination with the chemotherapy chlorambucil. Updated CLL11 trial data will be presented at the 2013 annual meeting of the American Society of Hematology (twitter #ASH13) in New Orleans from December 7-10. Gazyva is the first drug with a Breakthrough Therapy Designation to be approved by the FDA.
“Gazyva is an important new medicine for people with newly diagnosed chronic lymphocytic leukemia as it more than doubled the time a person lived without their disease worsening compared to chlorambucil alone,” said Hal Barron, M.D., chief medical officer and head of Global Product Development in a press release this morning.
Blog readers who attended the Roche analyst event in Chicago during the ASCO annual meeting in June will have noted that Roche’s long-term corporate strategy is focused on combining cancer drugs to improve treatment outcomes; a theme echoed by Charles Sawyers, President of the American Association for Cancer Research (AACR) during his ASCO Science of Oncology award lecture on “Overcoming Resistance to Cancer Drug Therapy“.
One of the combinations that Roche COO Daniel O’Day highlighted in the analyst event at ASCO was obinutuzumab/GA101 (Gazyva) with GDC-0199 (ABT-199) for the treatment of B-cell hematological malignancies such as CLL & non Hodgkin’s lymphoma (NHL). Obinutuzumab is a glyco-engineered CD20 antibody, while GDC-0199 is a Bcl-2 inhibitor. Both cause apoptosis (cell death) through complementary mechanisms of action.
An abstract on the preclinical data for this combination will be presented at the ASH annual meeting in New Orleans. A phase 1 clinical trial in CLL with this combination is currently underway and recruiting patients (NCT01685892).
I had the great pleasure at the recent AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics meeting in Boston to talk with Deepak Sampath, PhD the leader of Genentech’s Bcl-2 preclinical research about the rational for the obinutuzumab plus GDC-0199 combination.
In this SoundCloud, Dr Sampath introduces himself and what his lab does at Genentech: What he said during the interview makes for interesting reading, and suggests this combo could have blockbuster potential!
Subscribers to Premium Content can read a transcript of the interview below: