Biotech Strategy Blog

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

Posts tagged ‘daratumumab’

For years we’ve followed the trials and tribulations of targeted therapies seeing many approved and quite a few disappear forlornly (and officially) off to dog drug heaven. Many more sit in no-man’s land as companies eagerly wait in a holding pattern for other trial readouts in different tumour types. Sadly, sometimes these studies don’t generate enough compelling data either. With so much competition about, there are no shortcuts or low-hanging fruit in biotech or cancer drug development any more.

ASCO16 Chicago 1

En route to Chicago and ASCO!

Then along came antibody drug conjugates (ADCs), with some encouraging results in a range of cancers in both solid tumours and hematologic malignancies that lead to the approval of several new therapies.

After that, the next big advance was immunotherapies, specifically checkpoint blockade, with encouraging single agent activity in melanoma, lung, and even urothelial bladder cancer. We’ve also seen the promise fo combining two different checkpoints such as nivolumab and ipilimumab together in metastatic melanoma, albeit with an increase in toxicities.

This is all very well and good, although the challenge remains that the majority of patients either respond to therapy and relapse, or do not respond at all, depending on the circumstances, the tumour type and the regimen. We still have a long way to go in moving the needle and creating a new paradigm shift on a broad scale.

So what happens when we start to combine modalities – such as targeted therapies with immunotherapies?

Uh-oh, I hear the distant cries of disagreement erupt…

  • Remember vemurafenib plus ipilimumab in metastatic melanoma was scuppered by severe hepatitis?
  • What about osimertinib plus durvalumab in NSCLC and the increased incidence of ILD?

Both of these statements are true, and yet… we should not assume that all mixed therapy combination approaches are doomed on the basis of a mere n of 2. What happens if some are synergistic or additive? What happens of there are hidden gems that teach us new ways of doing things rather than doing the same old thing just because it’s always been done that way?

With this in mind, I’d like to open the door on our first ASCO 2016 Preview series with a look at novel combination approaches in development that caught my eye.

What are the early hints and signals that we can learn from the data? Which companies are evaluating imaginative new ideas that may turn the tables on traditional thinking?  The ideas discussed here may well surprise a few people.

To learn more, Subscribers can log-in below or you sign up for a subscription and join the ever burgeoning BSB club of sophisticated lay people – including investors and commercial/new product development people – who can really understand and appreciate the fundamentals of cancer R&D…

Aloha! The Eddie Aikau Big Wave surf contest only happens on Waimea Bay on the North Shore of Oahu in a year when there are 40 ft swells. It’s six years since the last one took place.

Surfing Waimea Bay

Waimea Bay Surfing on Feb 10th 2016

Yesterday, at the last minute the big waves failed to show up as an expected storm took a different track.

In R&D terms this is a bit like a phase 3 trial that was expected to be positive, only at the last minute reads out negative.

Last year was an exceptional year in multiple myeloma with several new approvals. It was a “Grand Cru” year, but there is already another wave on the horizon…

Whether it’s a 40 foot Eddie Aikau wave remains to be seen, just like the bay and weather dictates the waves, clinical trial data and physician experience ultimately drive uptake.

This post continues our in-depth post-ASH analysis and pre-TANDEM coverage, with a look at the new wave in myeloma that’s coming our way.

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ASH 2015 OrlandoOrlando – the 2015 annual meeting of the American Society of Hematology (Twitter #ASH15) kicks off in earnest today at the Orange County Convention Center.

There’s a comprehensive press program at #ASH15, which will no doubt drive a lot of the media coverage, but in addition to discussing some of the highlights, we’ll be going off the beaten path, and gathering noteworthy data for our post-meeting coverage.

There’s always a lot of great posters at the meeting, as well as useful educational and scientific sessions.

If you are interested in checkpoints in hematology, do check out the Scientific Session chaired by Dr Krishna Komanduri (@drkomanduri) “Checkpoint, Please?” It takes place from 9.30 am to 11 am today. It’s repeated again from 4 to 5pm on Sunday.

As the conference program notes, “this session will provide a broad overview of checkpoint inhibition and its therapeutic potential in the setting of solid tumors, alloreactivity and treatment of hematologic neoplasms.”

This is a rolling blog post, throughout the day we’ll be adding commentary as the opportunity presents.

Subscribers can login to read more or you can purchase access below.

This year has been an unprecedented Grand Cru year for the field of multiple myeloma, with no less than four drugs approved by the FDA to date… the fourth one just this morning while writing this preview!

  • Panobinostat (Farydak) in relapsed/refractory disease in combination with bortexomib plus dexamethsone after at least 2 prior therapies.
  • Daratumumab (Darzalex) received accelerated approval based on phase 2 data and is human CD38-directed monoclonal antibody that is indicated for the treatment of patients who have received at least three prior lines of therapy.
  • Ixazomib (Ninlaro) is the first oral proteasome inhibitor and is approved in combination with lenalidomide plus dexamethasone, in people who have received at least one prior treatment.
  • Elotuzumab (Empliciti) is a monoclonal antibody against CS–1/SLAMF7 approved today in combination with lenalidomide plus dexamethasone after 1–3 lines of prior therapy.

There are also many promising new agents in development and quite a few that may well not make it to market as a result of newer, better tolerated agents coming through.

To learn more about our insights on multiple myeloma, subscribers can log in or you can sign up below to read our latest ASH 2015 Preview.

Multiple myeloma (MM) has been very much in the news this week after the American Society of Clinical Oncology (ASCO) abstracts were released to much anticipation.

Myeloma is largely thought to be an incurable disease despite the option of an autologous stem cell transplant for newly diagnosed patients. That said, I have actually met some people who have had two or 3 transplants over several decades, a testament to their strength and fortitude in enduring such a challenging procedure.

This year, the news media have focused on elotuzumab (BMS/AbbVie), a CS1/SLAMF7 inhibitor that has previously shown clinical activity in earlier trials, after it was showcased in the ASCO Presscast last week. This why you see many articles on the data reported from this particular abstract.

New Orleans American QueenIt’s not the most exciting new data in this disease for me though, that honour goes to two other therapeutics of an entirely different kind. They come completely out of left field and what we saw over the last two months really caught our attention and may surprise you too.

Indeed, we saw hints of some of this data at the American Society for Gene and Cell Therapy (ASGCT) meeting last week in New Orleans.

To learn more about the exciting new developments in the field of multiple myeloma and what a leading thought leader had to say, you can sign in or sign up in the box below.

The ASCO 2014 annual meeting starts on Friday in Chicago and there’s some interesting Multiple Myeloma (MM) data that we’ll be covering.

This preview outlines which MM data may be noteworthy at ASCO and for those going, I’ve included the session times and locations so you can mark your dance card accordingly. There will be more on the potential commercial implications of the data once they have been presented.

Although ASCO is mainly considered a solid tumour meeting, it has not been without some excellent data on hematologic malignancies over the years.

ASCO will always have a particularly soft spot for me since we launched imatinib (Gleevec) for advanced CML on the Friday of ASCO way back in 2001. Many readers may know that I was in new products at Novartis Oncology and was heavily involved in bringing STI571, as it was originally known, to market and subsequently moved on to the brand team.

Gleevec on cover of Time MagazineThe meeting happened in a blur; on Friday we shipped drug for the first scripts the same day within hours of approval received that morning, flew to the conference, had a packed hall with standing room only for 2,000 people in a CME session in the afternoon, presented the one-year phase 3 IRIS data on the Monday, and received a very nice mention from Dr David Scheinberg (MSK), one of the phase 2 trialists during the Sunday plenary session. All these events occurred only a few days after hitting the front page of TIME magazine. It took quite a few weeks to come down from that incredible high!

When people insist ASCO is a solid tumour meeting, I always smile and remember that isn’t always the case.

Hematologic malignancies can generate excellent data mid year. This year, there is good news to discuss, not in CML, but multiple myeloma (MM) at both ASCO and at the European Hematology Association (EHA) Congress in Milan from June 12-15. There is also some nice CLL data, which I will cover in a separate Preview.

What’s different at ASCO this year?

This year, ASCO promises to offer some rather interesting data on some studies in multiple myeloma that missed the ASH deadline last September. You can’t always predict when a readout will occur, so good data can also abound at ASCO, EHA or the Lugano Lymphoma meeting.

As part of our commitment to continuous improvement, we plan a slightly different approach to the daily coverage for ASCO.

This year, we’ll be posting a live blog each day (for subscribers) where we’ll put quick comments about our impressions of data or our thoughts on what’s generating interest, short audio notes and excerpts of interviews with experts.

Given we’re in a lot of sessions and ASCO is pretty spread out (#BlisterWalk), so the live blog won’t be real-time, but we plan to make frequent updates to it during the day.

Please do check back at the blog for daily for updates and insights as they happen.

To learn more about our second ASCO Preview, which is on multiple myeloma, you can sign in or sign up below.

This year at the American Society of Hematology (ASH) there are over 800 abstracts on multiple myeloma alone. Obviously, one can’t possible do them all justice, but there are a number of important ones that are well worth highlighting, especially given the raft of new products in development, as well as some solid data from existing approved products.

Myeloma has long been dominated by proteasome inhibitors and immunomodulatory (IMiD) agents in combination with prednisone, dexamethasone, melphalan or as a triplet such as RVd, VMP etc. In Europe, melphalan still dominates as part of the base therapy, while in the US, dexamethasone (dex or simply d) is preferred partner since the tolerability is much improved along with a lower risk for secondary primary malignancies (SPMs).

In this detailed preview, the following companies and products are covered:

Companies: Millennium, Celgene, J&J, Amgen, Novartis, GSK, Array, Actelion, Biotest, KaloBio, Curis, Verastem, Karyopharm, Aeterna Zentaris.

Products: Ixazomib, lenalidomide, pomalidomide, carfilzomib, panobinostat, daratumumab, ibrutinib, CC-292, afuresertib, GSK2857916, ARRY-520, ACY-1215, indatuximab ravtansine, CUDC-907, VS-5584, selinexor, LCL161, BYL917, perifosine.

I also discuss some controversial topics such as lack of overall survival in the Revlimid trials and the risk of cardiovascular adverse events with Kyprolis. There are also an exciting raft of new compounds with new targets in various stages of development.

Obviously there will be more to come at the meeting, but for now, there’s plenty to discuss and review ahead of time.

Subscribers and those wishing to read the in-depth review by subscribing can click through the Tinypass box below to sign in or sign up – check it out!

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