Biotech Strategy Blog

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

Posts tagged ‘Multiple Myeloma’

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…

Jounce Poster AACR 2016

The AACR Poster Halls get packed quickly!

It’s time to change direction and take a look at some of the Gems from the Poster Halls at the recent American Association for Cancer Research (AACR) meeting.

One particular abstract that looked interesting related to the Aduro compound, BION–1301, which is a monoclonal antibody targeting the B cell Maturation Antigen and its ligand, A Proliferation Inducing Ligand (BCMA-APRIL) in multiple myeloma.

Increasingly, there has been a lot of clinical interest in the BCMA target, but what about APRIL?

We spoke to one of the scientists involved in the research about this novel agent:

“It is very effective at abrogating the activity of APRIL and, in particular, in our models blocks the growth, survival, drug resistance, migration and adhesion of myeloma cells both in-vitro and in-vivo in our murine models. These models have been predictive for clinical activity of other novel targeted therapies including lenalidomide and bortezomib, and so we think targeting APRIL represents a very promising strategy.”

Sounds pretty good, right?

To learn more about what they had to say about this approach, subscribers can log-in or you can sign-up in the blue box below.

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 Manic Monday

The #ASH15 wall of people marching to the poster hall just after 5pm

Orlando – it’s Monday at the annual meeting of the American Society of Hematology (ASH) annual meeting, a day I call “Manic Monday” because there are so many simultaneous sessions, you end up running around frazzled, in/out of sessions, in the hope of catching all the presentations of interest.

It’s particularly challenging if you are in a full session — you won’t be able to get back in if you leave — which results in having to make difficult choices on what to see and where to run to.  Some of the myeloma thought leaders were urging colleagues to tweet sessions they couldn’t be in, so “Manic Monday” may be a good time to contribute to the collective ASH Twittersphere.

We’re starting today’s rolling post with my notes from the lymphoma New Drugs session yesterday, then we’ll be updating the blog as the day goes by, as the opportunity permits.

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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.

It’s that time of the month where the BSB readers get their chance to put us on the hot spot!

SITC 2015 Land GrabHere, we take a look at reader questions that have been submitted and argue the toss – is there evidence preclinically or clinically that is useful or instructive?

We can’t promise to answer every question, sometimes there simply isn’t any data to help either way.

This week, the topic is CAR T cell therapies, a subject that seems to be very high on many people’s minds and many of you had similar questions, so here goes…  

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The immuno-oncology space continues to get both interesting and also very crowded with over 20 chimeric antigen receptor (CAR) T cell therapies now in development. Originally, the excitement began with the University of Pennsylvania’s dramatic announcement regarding the first two advanced CLL patients they successfully treated, leading to a collaboration with Novartis and spurring a new ‘arms race’ development in this niche.

While most of the CAR T cell therapy data since has largely focused on acute lymphoblastic leukemia (ALL) and to a lesser extent, non-Hodgkins lymphoma (NHL), many have been wondering what was happening on the CLL front?  Has hope been abandoned there or will we see a renaissance occur?  It is of particular relevance with the Abbvie/Genentech announcement that venetoclax has positive data in CLL patients who have the Del17p mutation and filing is likely here in this subset soon.  Therapies such as ibrutinib and idelalisib are already approved in refractory CLL and may also have a future role to play here.

Do we need suicide switches for CAR T cell therapies such as Bellicum and Cellectis are developing or not?

Meanwhile, other hematologic malignancies are also being explored, including multiple myeloma. Why would a CD19 CAR work in a disease long considered to be CD19-negative in advanced, refractory disease?

Carl June UPenn

Dr Carl June, U Penn

What about progress with solid tumours? Many commentators and investors have been highly sceptical of the chances of success here following the advent of positive checkpoint data beyond metastatic melanoma and early CAR data in mesothelin cancers.

To answer these questions and also get a flavour for where things are headed with CAR T cell therapies, we recently interviewed one of the leading experts in this field, Dr Carl June (U Penn).

To learn more about Dr June’s perspective, subscribers can log in below or you can sign up in the box.

Last month’s Biotech Strategy mailbag – where we answer questions from subscribers – turned out to be rather controversial with strong feelings running in several camps on Puma Biotech’s neratinib in breast cancer.

This time around we have a bunch of questions on completely different topics and compounds to cover:

  • BRAF plus MEK and/or immunotherapy in BRAFV600 metastatic melanoma
  • Immunogen’s IMGN853 – now known as mirvetuximab soravtansine – in platinum resistant ovarian cancer
  • AbbVie/Genentech’s ABT–199/GDC–0199 venetoclax

To learn more about our insights, subscribers can log in or you can sign up in the box below.

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 big news yesterday evening was that Amgen’s phase III FOCUS trial in relapsed/refractory multiple myeloma failed to meet its primary endpoint of overall survival (HR=0.975).

Kyprolis logoSuch a marginal hazard ratio (HR) tells us that the risk of death was not reduced by taking carfilzomib over best supportive care.

According to the company:

“The 315-patient, open-label study evaluated single-agent Kyprolis® (carfilzomib) for Injection compared to an active control regimen of low-dose dexamethasone, or equivalent corticosteroids, plus optional cyclophosphamide in patients with relapsed and advanced refractory multiple myeloma. Nearly all patients in the control arm received cyclophosphamide. Patients were heavily pretreated and had received a median of five therapeutic regimens prior to study entry.”

To learn more about our insights and thoughts on this data, you can sign in or sign up below.

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