Posts from the ‘Biotech Strategy Blog Posts’ Category
The challenge of Tumor Lysis Syndrome in Hematology New Product Development
February 20th, 2013
Daedalus
Tumor Lysis Syndrome (TLS) has been in the news recently as a result of two patient deaths in a chronic lymphocytic leukemia (CLL) clinical trial with AbbVie’s ABT-199, a novel BCL-2 inhibitor in early stages of development.
What is TLS and why is this important in cancer research was subsequently analyzed by Icarus Consultants hematology industry expert, Sally Church, PhD on Pharma Strategy Blog.
Sally notes in her post, “we don’t yet know whether the effect in ABT-199 is a dose-schedule issue or a compound structure issue (especially given the reformulation from the original navitoclax issue).”
It’s a major setback to AbbVie ($ABBV) when the company was poised to start a phase 3 clinical trial with ABT-199 in CLL.
AbbVie will have to convince doctors that careful dose scheduling can solve the problem of a drug that may be too potent for the body to handle. Further deaths due to TLS could easily stop the development of this compound.
The setback to ABT-199 is, however, good news for ibrutinib that along with ABT-199 is in a race to market in CLL.
On February 12, 2013, ibrutinib received “breakthrough designation” from the FDA for the treatment of mantle cell lymphoma (MCL) and Waldenstrom’s macroglobulinemia.
Breakthrough designation means that a drug can be approved on the basis of early clinical data. Depending on when filing takes place, FDA approval of ibrutinib in MCL could be forthcoming later this year.
We expect to be producing a report on the CLL new products in development soon. This will cover some of the challenges and issues companies are facing. If you haven’t already done so, please sign up below if you would like to receive news alerts and be the first to know when reports are available.
The annual meeting of the American Association for Cancer Research (AACR), held in Chicago earlier this month, is one of the most important meetings of the year for cancer scientists, pharma/biotech drug development and new products professionals.
Bill Sellers, in the AACR plenary session, described how Novartis are using the Cancer Cell Line Encyclopedia (CCLE) in conjunction with the Broad Institute to identify promising new compounds.
As Sally Church, PhD noted on Pharma Strategy Blog in her post on the highlights of AACR 2012:
“What made the meeting exciting for me was the sheer number of new compounds emerging from late preclinical to early phase 1.”
Two of the many promising new drugs in early stages of development were highlighted on Biotech Strategy Blog:
AZD3514 (AstraZeneca), a selective androgen receptor down regulator (SARD) in phase 1 clinical trials for castration resistant prostate cancer (CRPC).
ABT-199 (Abbott), a new Bcl-2 inhibitor (that improves on navitoclax), in phase 1 drug development for chronic lymphocytic leukemia (CLL).
There were many noteworthy posters presented at AACR particularly from young researchers
e.g. “Overcoming resistance to EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer” was a poster that suggested the prospect of future drug development targets.
During the high quality poster and oral sessions, we met numerous people including CEOs of baby biotechs, young researchers and clinicians with an interest in translational research, including Laura Strong, Ph.D President & COO of Quintessence Biosciences (@scientre), David Woessner who was presenting his PhD research (@pinfoto) and Philippe Aftimos, MD from Belgium (@aftimosp), all of whom were actively sharing their observations during numerous sessions via Twitter during the conference.
The annual meeting is not just about basic science though, but also drug development strategy and emerging research trends, such as the automation of preclinical drug discovery, as well as the collaboration between academia and Pharma/Biotech in combination clinical trials using two novel compounds from different companies. This last trend, I am pleased to say, has already begun and will hopefully continue apace in the future.
If you were not able to attend AACR, then Sally Church aggregated all the #AACR tweets from the meeting on Pharma Strategy Blog. AACR also have webcasts of some of the sessions available, including some with free access.
We’re already looking forward to AACR 2013 in Washington, DC and the timing of the meeting means it should take place when the renowned Cherry Blossom are in full bloom. Hopefully, this will provide a great opportunity for another Pharma Strategy Blog video!
The prostate cancer market continues to evolve at a fast pace. Companies with products on the market or in development will need to adapt their marketing strategy to the changing prostate cancer market dynamics. Some of the recent news includes:
MDV3100 shows 4.8 improvement in median overall survival
Sally Church, PhD on Pharma Strategy Blog interviewed David Hung, MD CEO of Medivation and discussed the MDV3100 clinical trial data presented at ASCO GU.
Sally has been following the development of MDV3100 for a while, and previously interviewed Dr Charles Sawyers one of the co-developers.
MDV3100 showed an improvement in median overall survival of 4.8 months in advanced prostate cancer, and offers a number of significant advantages over abiraterone acetate (Zytiga) due to its different mechanism of action on the androgen receptor.
One of the advantages is it’s ability to target splice variants:
You can read more about MDV3100 on Pharma Strategy Blog.
Is ARN-509 more effective than MDV3100?
Another interesting compound in prostate cancer drug development is Aragon’s ARN-509. Recent research published in the AACR journal, “Cancer Research” suggests that ARN-509 may be a more potent androgen-receptor antagonist than MDV3100.
Whether ARN-509 will make it to market remains in question given that Medivation claim the compound was part of the intellectual property it acquired from UCLA along with what became MDV3100.
You can read more about the potential of Aragon’s ARN-509 in prostate cancer on Pharma Strategy Blog.
Radium-223 (Alpharadin) significantly prolongs time to first Skeletal Related Event
Pieter Droppert has written on Biotech Strategy Blog about the radium-223 (Alpharadin) clinical trial data presented by Dr Oliver Sartor at ASCO GU.
Alpharadin is a bone targeted radiopharmaceutical that has shown not only a significant delay in the time to first skeletal related event (SRE) but an increase in overall survival.
Dr Sartor kindly offered some clinical perspective on the data that you can read on Biotech Strategy Blog.
In case you missed it, the video interview with Dr Chris Parker at ECCO/ESMO 2011 in Stockholm offers further information on radium-223 and the ALSYMPCA trial results:
Amgen fails to convince ODAC that Xgeva should have a prostate bone mets indication
If you were following the prostate cancer news this past week, then the ODAC 12:1 vote against granting an indication for denosumab (Xgeva) for the prevention of prostate cancer bone metastases was in the news
Pieter Droppert collated the Xgeva ODAC meeting tweets on Storify if you are interested in what was live tweeted during the meeting.
Once Alpharadin is approved will radiation oncologists now get more involved in the treatment of prostate cancer and how will this impact the market dynamics? Will urologists favor MDV3100 that does not require administration of prednisone at the expense of Zytiga?
Companies will need to adapt their marketing strategy as new prostate cancer new products come to market in 2012.
Deserted River Walk due to San Antonio cold weather
If you are interested in news from the San Antonio Breast Cancer Symposium (SABCS) then Sally Church, PhD has a number of reports on Pharma Strategy Blog that are worth reading.
SABCS Video Preview
In her preview of the SABCS meeting (that you can also watch below), Sally reviews some of the BOLERO-2, CLEOPATRA and NEOSPHERE clinical trials, and what impact positive data may have on breast cancer patients. It is well worth watching.
SABCS Twitter Coverage
Although there is no wifi in the meeting rooms at SABCS, a few scientists, patients advocates and physicians are tweeting from the meeting including @drsteventucker and @teamoncology. You can easily follow the twitter conversation and check-out what’s been said through the #SABCS aggregator on Pharma Strategy Blog. As Sally would say, “check it out!”
As an example of how effective social media can be to share information, Pieter Droppert (@3NT) used storify to share some of the insights posted on twitter during the SABCS plenary lecture he attended on potential of macrophages as breast cancer drug development targets.
Breast Cancer and the Environment
Pieter also commented on the recent Institute of Medicine (IOM) report on “Breast Cancer and the Environment” which was somewhat disappointing to those hoping that it would highlight causal links.
Hot news at SABCS
This year the San Antonio Breast Cancer Symposium had a lot of exciting new data. Two papers on the BOLERO-2 and CLEOPATRA trial data was published during the meeting.
Some of the interesting early data presented at the meeting included work on Notch inhibition to reduce aromatase inhibitor resistance, HER2 mutants and targeting HER3. You can read more updates from Sally Church on Pharma Strategy Blog.
Overall, this was one of the most interesting SABCS meetings of recent years with a good balance of science and clinical data.
Hopefully next year, there will be more discussants to put the data in context, as this would have made it an even better meeting.
There was a lot of interesting science at the recent AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics international conference in San Francisco.
In particular, the poster sessions offered the opportunity to discuss pre-clinical and early drug development work, and share insights into pathways and mechanisms of action. If you are in new product development, it’s a key meeting to attend.
What was the news at AACR molecular targets?
Sally Church on Pharma Strategy Blog aggregated the live tweets from the joint AACR-NCI-EORTC meeting, although the absence of wifi in the plenary sessions meant that there were fewer tweets than might have been expected.
Sally has written about some of the data presented on breast cancer at the meeting. In her insightful post she reviews the Syndax data for entinostat in second-line ER/PR+ breast cancer, and also asks whether ALK is a new target in inflammatory breast cancer (IBC)?
From what was heard at the meeting, there will be a lot of new breast cancer data at the forthcoming San Antonio Breast Cancer Symposium (SABCS) that Sally will also be attending.
More insights from AACR molecular targets will be available on Pharma Strategy Blog in the next few days.
Meanwhile on Biotech Strategy Blog, Pieter Droppert has written about some of the sessions he attended in San Francisco on:
- Overcoming barriers to new cancer drug development
- Improving cancer clinical trial design
- Prostate Cancer
Next year’s 2012 molecular targets meeting will be in Dublin, good news for all those who like Guinness!
At Icarus Consultants, we help pharmaceutical and biotechnology companies bring new products to market.
When we look at the market opportunity for a new product, it’s not enough to have a great product, key to success is getting paid for it. Pricing and reimbursement are important in the commercial strategy!
Is it better to obtain the highest price for a new targeted therapy or alternatively have a lower price and obtain more market share? From a marketing strategy perspective, there is sometimes a case to be made for a lower price, but it’s a hard sell to convince senior management they are not leaving money on the table.
As to cancer immunotherapy, Dendreon with sipuleucel-T have shown that it can offer a survival benefits to some cancer patients. Other vaccines and immunotherapies are in development.
However, as Pieter Droppert points out in an insightful post on Biotech Strategy blog about a pilot study for PANVAC (Bavarian Nordic, CV-301), there remain a number of challenges that still have to be overcome. These include:
- How do we identify upfront which patients will respond to the vaccine?
- How do we evaluate how well patients are doing without clinically validated surrogate markers to aid in assessment?
You can read more on Biotech Strategy Blog.
There is a plenary session on cancer immunotherapy at the AACR-NCI-EORTC Cancer Molecular Targets & Therapeutics conference that starts in San Francisco tomorrow.
We look forward to obtaining further insights on the opportunities and challenges with cancer immunotherapy at this meeting.
The Society for Translational Oncology (STO) recently held a prostate cancer symposium in Belfast.
In a post on Biotech Strategy Blog, Pieter Droppert reviews the STO video discussion on “Prostate Cancer: Progress & Promise”
One of the key insights is that targeting ERG signaling may be key to treating prostate cancer, and that ERG becomes a druggable target by inhibiting PARP.
Sally Church has written about the work of Arul Chinnaiyan’s lab on TMPRSS2:ERG and how this may be a more useful marker than PSA in prostate cancer.
You can read more on Pharma Strategy Blog about whether personalized therapy for prostate cancer is possible?
Sally will be attending the American Association for Cancer Research (AACR) special conference on “Advances in Prostate Cancer Research” in Orlando from February 6-9, 2012.
Co-chaired by Arul Chinnaiyan and Charles Sawyers, the meeting features plenary sessions on genomic and molecular profiling, prognostic signatures, androgen receptor signaling, drug development, ETS gene fusions, prostate cancer initiation and progression, and imaging.
If you have an interest in prostate cancer drug development and translational research this meeting looks well worth attending.
The fast moving prostate cancer market took another leap forward last week with the announcement of positive phase III data for Medivation’s MDV3100.
As reported by Sally Church on Pharma Strategy Blog, Medivation announced that the interim analysis of the AFFIRM trial showed a 4.8 month increase in overall survival (OS) compared to placebo.
Although this is only interim and not final data, Sally observed:
“the 4.8 month improvement in OS in post-chemo setting is superior to that previously seen reported for abiraterone (Zytiga), which had a 3.9 month advantage over placebo.”
Pieter Droppert on Biotech Strategy Blog noted, MDV3100 and Zytiga have completely different mechanisms of action in advanced prostate cancer.
MDV3100 is an androgen receptor blocker, while Zytiga is an androgen biosynthesis inhibitor. This distinction is key. Zytiga inhibits the CYP17 enzyzme complex required for androgen biosynthesis. However, a consequence of CYP17 inhibition is an increase in mineralocorticoid levels, which can lead to hypokalemia, hypertension, fluid retention.
The result is that Zytiga requires coadministration of a corticosteroid (prednisone) to reduce the incidence and severity of potential mineralocorticoid adverse reactions.
MDV3100 does not require the administration of a steroid, which is a big advantage to patients. Instead it blocks the androgen receptor (AR) that is highly expressed on prostate cancer cells.
Cora Sternberg presents Prostate Cancer Educational Symposia at EMCC 2011 in Stockholm
There are a lot of new products in the pipeline for prostate cancer including TAK-700, Cabozantinib (XL184), radium-223 chloride (Alpharadin), BPX-101, Prostvac-VF, ipilumumab, Custirsen (OGX-011), dasatinib (Sprycel), lenalidomide (Revlimid) and ARN-509 to name a few.
The prostate cancer market is forecast to grow from $1B to $5B by 2015 as new products are approved and new treatment options become available. This is good news for advanced prostate cancer patients.
Richard Steinman from the University of Pittsburgh School of Medicine in “The Oncologist” (the journal of the Society of Translational Oncology), comments on the importance of the noncancerous cells in tumors (the stroma):
“The stroma, including fibroblasts, adipocytes, endothelial cells, and immune cells, had been demonstrated to provide critical metabolites to cancer cells and engages in tumor-promoting crosstalk with cancer cells.”
PET scan of enzyme MAO-B Image Source: NIH
Recent research has shown the ability to image metabolic markers of tumor activity. On Biotech Strategy Blog, Pieter Droppert writes about a metabolic marker of malignant glioma cells, 5-ALA (5-Amino-Levulinic-Acid) and how this may help glioblastoma surgery.
Meanwhile on Pharma Strategy Blog, Sally Church discusses the use of folate receptor alpha fluorescence imaging in ovarian cancer.
Imaging of metabolic markers may assist in the identification and targeting of critical mediators of cancer-stromal crosstalk. This is an interesting area to watch.
The forthcoming AACR-NCI-EORTC conference on Molecular Targets and Cancer Therapeutics has a plenary session on “Targeting the Tumor Stroma Interaction.“