Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts by MaverickNY

JAK2 inhibition in hematologic conditions

By on December 3, 2009

The last few weeks have seen several emails from Pharma Strategy Blog readers and clients asking about JAK2 inhibition and it's importance in cancer, so we thought it was a good time to summarise the pathway with ASH imminent.

Here's how the JAK2 (Janus) pathway connects strategically in the wider scheme of things:

STI_v1
Source: Wikipedia

As the chart shows,blocking JAK2 may block cytokine signaling, which is associated with the build up of fibrosis in myelofibrosis disorders. 

Why is JAK2 relevant in hematology? 

According to the Oregon Health Sciences University (OHSU) Molecular Diagnostic Center (downloadable PDF), patients with myeloproliferative disorders carry a V617F JAK2 mutation:

  • 74 – 97% of patients with polycythemia vera (PV)
  • 33 – 57% of patients with essential thrombocythemia (ET)
  • 35 – 50% of patients with myelofibrosis (IMF)
  • Also present infrequently (3-5%) in myelodysplastic syndrome (MDS) & CMML
  • JAK2 V617F mutation (auto-inhibitory domain) activates the kinase

Testing for the mutation also helps confirm these clinical diagnoses.

Drugs in development

There are several compounds targeting the JAK2 mutation in development.  They include:

  1. INCB018424 (Incyte/Novartis)
  2. TG101348 (TargeGen)
  3. CEP-701 (Cephalon)
  4. AZD1480 (AstraZeneca)
  5. XL019 (Exelixis)]
  6. WP1066 (Calistoga)
  7. CYT-387 (Cytopia)

Incyte recently signed a licensing deal with Novartis, for the JAK2 inhibitor, which has completed phase II trials.  According to the company, the compound works by blocking cytokine signalling:

Picture 39Source: Incyte Corp.

Interestingly, in the article by Garber (below), Dr Moshe Talpaz, a world recognised hematologist, was quoted as saying that the JAK2 inhibitors, "Preclinical was much more impressive than clinical" based on his experience with TargeGen's agent because fibrosis was not reversed.

At the ASH meeting this weekend, the leading JAK2 company, Incyte, will be presenting  three key papers on INCB018424, the compund they are developing with Novartis:

  • A Phase II Study of INCB018424, An Oral, Selective JAK1/JAK2 Inhibitor, in Patients with Advanced Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Refractory to Hydroxyurea
  • Significant Activity of the JAK2 Inhibitor, INCB018424 in Patients with Secondary, Post-Myeloproliferative Disorder Acute Myeloid Leukemia: Results of An Exploratory Phase II Study
  • Long-Term Follow up and Optimized Dosing Regimen of INCB018424 in Patients with Myelofibrosis: Durable Clinical, Functional and Symptomatic Responses with Improved Hematological Safety

What is the potential impact of JAK2 for people with myelofibrosis?

More information will be reported from ASH meeting on this blog as the data is presented in New Orleans over the weekend. 

It will be interesting to see how good the agent is and what exactly Novartis, who are leading the commercial development, have on their hands.  In case anyone is wondering, both PV and ET are rare orphan diseases, meaning they affect less than 200,000 people per year, with an approximate prevalence of around 40-50K each in the USA, if memory serves me correctly.

ResearchBlogging.orgGarber, K. (2009). JAK2 Inhibitors: Not the Next Imatinib But Researchers See Other Possibilities JNCI Journal of the National Cancer Institute, 101 (14), 980-982 DOI: 10.1093/jnci/djp216


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USPSTF Members Defend New Guidelines Before Congress

By on December 2, 2009

Ned Calonge, MD, chairman of the USPSTF said the guidelines, which have drawn a “remarkable amount of attention,” were communicated poorly.

The group did not mean to tell the public that women under 50 shouldn’t have mammograms, Calonge said, rather, it meant to convey that the test for women under 50 is supported by only limited clinical evidence, and that all women should discuss the risks and benefits with their physicians.

via medpagetoday.com

Interesting that the task force chairman has finally clarified the USPSTF’s position amongst all the misinformation, misinterpretation and miscommunication surrounding the mammogram guidelines.

What’s surprising is that there was:

a) no radiologist on the committee
b) no formal communication plan to patients and physicians

The end result?

A major controversy that could have been largely avoided with more thought for the consequences of a “C” grade i.e. limited evidence supporting mammograms under 50 so patients would be informed of the risk-benefit trade-off before deciding upon whether to undergo testing.

Although medical services receiving an A or B grade will likely get compulsorily covered by insurance companies, it is still unclear what will happen with C grade procedures.

Caveat emptor. A storm that surely could have been avoided.

Posted via web from sally church’s posterous

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Risk Info in Pharma Ads Ignored by 41% of Consumers

By on December 2, 2009

The study found that the top ways consumers prefer to see prescription-drug risk disclosures presented online are:

  • Direct links to an independent website such as WebMD (32%).
  • Having a condensed version of risk disclosures available one click away (27%).
  • A direct link to a pharmaceutical company that provides the information (26%).
  • A direct link to a government website that provides the information (25%).
via marketingcharts.com

It seems that the lack of attention to risk information was highest in those 55+.

Interestingly, the chief research officer for the study by ORC guideline suggested that:

“As consumers utilize a wide variety of sources to learn about prescription medications, it may not be optimal for the FDA to require that pharmaceutical companies include the same details in each of the channels they use to communicate information about their prescription drug products.”

The value of independent websites in providing accurate and fair balanced information is growing in importance, especially as the study also demonstrated that only half (50%) pay attention to disclosures in print ads. Whether this is due to information overload or the small size of the print is, however, unclear.

Posted via web from sally church’s posterous

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Between the Lines – Proto Magazine – Massachusetts General Hospital

By on December 2, 2009

By using language- and pattern-analyzing software to search and distill the cascade of words on social networking sites, researchers may be able to identify trends and signals, such as repeated mentions of a certain drug in connection with a particular side effect or treatment success. “Listening” to thousands of patients as they discuss treatments, side effects and experiences with their diseases might even help scientists come up with hypotheses worthy of study. “There’s a tremendous amount that goes on in a patient’s daily life,” says Frank Moss, director of the Massachusetts Institute of Technology Media Lab, an emerging-technologies research group that helped create one disease-related networking site, and a founder of the cancer drug company Infinity Pharmaceuticals. “They’re trying off-label drugs, different diets, different exercise, different lifestyles. That information isn’t easily available to clinicians, but the cure to the disease may lie within it.”

via protomag.com

This is an excerpt from the Massachusetts General Hospital quarterly magazine, Protomag, which you can also read online, via the link above.

The article isn't just about data mining, but also about how patients can connect and converse about their disease through forums as well as the dangers of social media sites that are unchecked by authorities (viz the FDA).

The 'deep web' as Gilles Frydman described it in the comments to the recent post on this blog about the FDA, social media and patients, has both advantages and disadvantages. One the one hand, it is a great resource for people needing advice from others with the same condition and on the other, it can be a fertile ground for misinformation and unscientific data with no substance or rigour.

Check out the full article in Protomag, it's well worth reading.

Posted via web from sally church's posterous

ASH – what's hot news this year?

By on December 2, 2009

On Friday, many of us interested in hematology and oncology will be heading to New Orleans and the annual American Society of Hematology (ASH) meeting.  Every year, I like to try and predict what might be hot topics beforehand, although I'm not always right!

So without breaking any embargoes, based on companies, drugs, and data that I've been following this year, here's my list of Pharma companies to watch out for:

  1. Celgene: Revlimid is doing well in the refractory setting and will likely have some stunning data in the front-line setting in multiple myeloma.  Data was released in July this year suggesting that patients live longer on the drug, paving the way for maintenance therapy as a viable option.  This is not good news for Millennium and J&J in the long run, who promote Velcade.  However, in the short term, Millennium still have a huge advantage over their rivals given they they have demonstrated long term survival data in the newly diagnosed setting, which Revlimid does not have.  It's clearly time to step up the R&D and marketing efforts a few notches now that the competition is getting hot.  Millennium do have a promising neddylation inhibitor, MLN4924, up their sleeve and I'm looking forward to seeing the latest data on that too.
  2. Novartis: Tasigna front-line data is being presented as a late breaking abstract suggesting that is achieves deeper and earlier complete cytogenetic responses than Gleevec, the standard of care.  It looks like the company will have likely beaten BMS and Sprycel in the race to file the 2nd generation TKI's in newly diagnosed CML.  Afinitor is being developed beyond renal cell carcinoma in many indications, including NHL.
  3. GSK: Arzerra has now been approved for the treatment of chronic lymphocytic leukemia (CLL) in patients who have become refractory to fludarabine and alemtuzumab.  Updated data in NHL is expected at this meeting.

Biotech companies also look to be well represented, although most of the data will be phase I and II, rather than big phase III studies:

  1. Onyx/Proteolix: Carfilzomib is a 2nd generation proteasome inhibitor that appears to spare patients some of the peripheral neuropathy associated with Velcade.  The agent has been doing well in trials to date and new, mature data is expected at ASH.
  2. Ariad: AP24534 is a TKI which appears to inhibit the T315i mutation not targeted by imatinib, dasatinib or nilotinib.  Although this mutation is rare, it is fatal as there are no approved options to target it at present.
  3. AEtena Zentaris/Keryx: Developing perifosine in myeloma.  Combination data with Velcade and dexamethasone is expected to be presented at ASH, see the link to the press release on the poster below.
  4. Seattle Genetics: Have had a rocky ride lately with the halting of dacetuzumab in combination with rituximab in diffuse large cell B-lymphomas but are presenting an update at the meeting.  They have another compound, brentuximab, in development for CD-30+ lymphomas.
  5. Trubion: TRU-016 is an anti-CD37 small modular immunopharmaceutical (SMIP™) protein in development for CLL, which they licensed from Facet. It's far to early to tell whether this agent has any promise, but worth watching, just in case.

Of course, there are also some others, such as Allos Therapeutics pralatrexate and Gloucester Pharma's romidepsin, but these have been recently approved in rare forms of NHL, ie PTCL and CTCL respectively. It will be interesting to see how and where they plan to expand to other indications outside the orphan drug designated initial approvals.

Calistoga and Semafore are both developing PI3 Kinase inhibitors in hematologic indications such as refractory B-cell malignancies and myeloma, respectively.  The data is still very immature, being phase I trials, but worth looking at since many of the big pharma company PI3 kinases are being tested in solid tumours rather than hematological cancers.

I'll be posting daily reports from the ASH meeting, so watch this space!

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FDA, social media and patients

By on November 30, 2009

:Original raster version: :Image:Food and Drug...Image via Wikipedia

Last month, the FDA held open hearings to debate the topic of social media guidelines for the pharma and biotech industry.  I was following from afar on my iPhone at the NY Chemotherapy meeting, as this was the first such hearing since 1996 and many in the industry were excited that the FDA at ,east appeared to be listening and finally getting social media. 

Several things struck me at once while following the Twitter stream on Fabio Gratton's excellent custom site for the purpose, FDAsm.com:

  1. There were a lot of agency people presenting (some argued they had a vested self interest)
  2. Not many pharma people were actually presenting (despite griping about the lack of guidelines in this space)
  3. Not many patients or patient advocacy groups were involved either.

What was also interesting was that there was plenty of justification for the use of social media, but very little in the way of practical solutions and suggestions that the FDA could consider, thus speeding up the process.

In the past, the FDA have claimed that it is all about the message not the medium, witness sending 14 pharma and biotech companies letters back in April this year for their Google ads with 1 or 2 clicks from the full safety information.  However well intentioned the wrist slap was, it ws later shown to negatively affect public health, as some of the presenters at the meeting clearly showed. 

Rather than look at this incident negatively, I wondered if the respectful and interesting interactions between the FDA DDMAC and industry seen at the hearings could not continue in the same vein on a more frequent basis.  Dialogue and discussion make for much more constructive rather than destructive relationships.

There are several things I'd like to point out about safety and adverse events (AE's):

  • They happen, no drug is immune from them, so best not to avoid them
  • Have policies and procedures for easily recording and submitting AE's
  • The currernt MedWatch reporting system is awful and cumbersome to use
  • If there was a better system, more doctors and patients would be more likely to report them
  • Social media could be a great tool for improving the MedWatch system, reaching more people, more easily and collating the relevant information

What was particularly poignant about these hearings is that, for me at least, a great chance was missed to put patients front and centre, whether this was in the form of better public health information and education or looking at ways to improve clinical outcomes.

Are patients really out of sight and out of mind?

The FDA will still be collecting comments and suggestions until February 2010, so if you missed the hearings this month, please do take the time and contribute offline.  The link to the FDA is here type in FDA-2009-N-0441 in the search box and it will bring up the dockets for comments.

In the meantime, John Mack of Pharma Marketing News is also running an anonymised survey to gather feedback and further suggestions post meeting and will send the aggregated results to the FDA.  Click here to make your views known!

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Things to be thankful for

By on November 27, 2009

The day before Thanksgiving, I spent a delightful afternoon here in San Diego with Mary Canady of Conprendia (@comprendia on Twitter). She runs a company specialising in Biotechnology Marketing. The beauty of meeting people like Mary on Twitter is the opportunity the platform offers for impromptu tweetups as you travel the world or even in your local area. Go check her out, she had some cool stuff for bootstrapping your marketing if you’re a small company on a tight budget.

While walking around the park, we came across the botany pavillion. I love these little treasures, there’s always some stunning flora and fauna to photograph, as the picture in this post shows.

Sometimes, we need to remember that for all the noise we make about healthcare and drug development (in any therapy area), it is ultimately the simple things that matter… a shared experience, a photo, an understanding. Listening goes a long way. Yesterday, while visiting the family of @MrGunn for a truly sumptuous Thanksgiving spread, I received a text message from a client. Not work related, but a short message wishing me a happy Thanksgiving. Very touching.

Years ago, when I was a child stuck in a shockingly grey bleak hospital awaiting surgery to remove a tumour, a dear friends Mum waltzed in and presented me with a huge bright purple flower in a pot. It was truly stunning and that simple gesture brightened up the place for everyone no end.

So this Thanksgiving the purple flowers in the botanical garden reminded me to be thankful to be alive 30 years on.

What are you thankful for?


Things to be thankful for

Commentary on the breast cancer controversy

By on November 26, 2009

After the recent furore over the breast cancer guidelines, I’ve been ignoring the hype and hysteria in the news and quietly waiting for some thoughtful commentary from some breast cancer experts I respect.

This morning I got my wish with an email alert from the New England Journal of Medicine. In it, two well respected breast cancer physicians from rhe Dana Farber Cancer Insitute have summarised their views in an editorial. You can read the whole commentary for free here:

http://content.nejm.org/cgi/content/full/NEJMp0911288?query=TOC

One point in particular struck me. The guidelines apply to those who are low risk, implying those women who are high risk (family history of breast or ovarian cancer, BRCA1 or BRCA2 positive etc), should still continue as before.

Their sensible and well thought out article is worth reading carefully and sharing with others.

A lot of people gave asked me what I’m going to do or would advise as one of those forty something women.

Well, I have a baseline and have been adjudged to be high risk so providing my insurance carrier is agreeable, I’ll be continuing with annual mammograms at NY Weill Cornell imaging center. This last point is important. My own experience of mammograms in suburbia was less than satisfactory and I would absolutely advocate going to get any tests at a cancer center where they have the latest technology and the best teschnicians, radiographers and pathologists. It does make a difference, possibly even between an accurate result and a false positive or negative.

Once you reach 40, politely insist on a baseline at your annual physical and get tested for BRCA1 and 2, after all that distinct aunt wasn’t aware in time and you don’t want to make the same mistake. These mutations drive aggressive breast and ovarian cancers. The most important thing is to get a baseline done, that gives you a comparion from which any changes can be detected early.

Check out the article and let me know what you think in the comments below.

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Hitting the blind side

By on November 25, 2009

This week I’ve been reading a fascinating book about Michael Oher’s journey to the NFL. The title?

The Blind Side.

And then I had a thought. That’s exactly what the cancer cell aims to protect it’s blind side from assault.

New developments in cancer (and peobably other therapy) treatments will come when scientists think strategically about attacking the vulnerabilities that either negate that protection or find new create ways to kill the menace.

Chemotherapy was used as blunt tool in the same way Lawrence Taylor was a one man sacking machine for the Giants. As offences evolved, smart defensive teams switched from a 4-3 to a 3-4 and had large, agile and athletic ends rush the passer. Strategy in football is constantly evolving on offence and defence.

What do we need now?

Maybe some creative and subtle gadget plays, such as nanotechnology approaches mentioned in the post on pancreatic cancer.

Or perhaps just thinking strategically out of the box as Gail Roboz did when she asked at the Chemotherapy Foundation, “why can’t we keep more people in remission?”

There are many other interesting examples evolving and being tested in company pipelines right now, as the Novartis-Incyte deal shows.

I’ll be interested in reporting what new at ASH next week: watch this space for more details!

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