Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts by MaverickNY

Pharma Strategy Blog conference newsletter is finally here!

By on November 1, 2010

By popular request, we are now rolling out the PSB conference newsletter.

This will be an occasional event that will be sent out after some scientific meetings we’ve attended.  They will contain snippets and summaries of data or new drug classes that we found interesting and worth highlighting and will be an adjunct to the blog, so you won’t get the same things twice 🙂

The first one will roll out by the end of this week and cover last week’s meeting from AACR on colorectal cancer biology.

You can sign up in the side bar on the top right —->

If you are a subscriber for this blog, you still need to opt-in to receive the newsletter. Sorry for the inconvenience, but personally, I hate it when people use my email address to send me things I didn’t request, so the same courtesy is extended to every one here too.

If you wish to stop receiving the newsletter, you can easily unsubscribe with 1-click.

4 Comments

Crizotinib in ALK-rearranged cancer mutations

By on November 1, 2010

While reading the latest New England Journal of Medicine, it was hard not to notice the focus on ALK mutations and crizotinib (Pfizer), with four articles in all on the topic, including a full original article, two brief reports and an editorial to boot.

Historical background

Gradually, we are gradually seeing more specific molecular markers and targets evolve in non-small cell lung cancer (NSCLC), which is a particularly difficult cancer to treat. This is good news because if we have a relevant target, we can treat subsets of patients with specific drugs and increase their chances of better outcomes while sparing those who are unlikely to respond from the systemic effects of a potent drug. Many call this ‘personalised medicine’ but I prefer to think of it as targeted therapy, because we are essentially matching the drug to the patient’s needs using biomarkers.

The first mutation that evolved in lung cancer, epidermal growth factor receptor (EGFR), was shown to be important in a subset of patients who tested positive for the activating mutation and tend to do well on EGFR therapy with drugs such as erlotinib (OSI/Roche/Genentech) or gefitinib (AstraZeneca).

Originally, two groups reported the discovery of the anaplastic lymphoma kinase (ALK) fusion gene in lymphoma in 1994.  Once translocation has occurred between the EML4 and ALK genes it produces a fusion gene, EML4-ALK, which generates aberrant signaling in cancer.

There was, however, much buzz and excitement three years ago when Japanese researchers reported activating mutations or translocations of ALK in NSCLC. Soda et al’s seminal 2007 paper in Nature is well worth reading from a historical perspective (the link below offers a rare free download from the publishers). As far as I can tell from the literature and talking to lung cancer specialists, the ALK mutation occurs in approx 2-7% of lung cancers. This may sound like a small number, but right now we don’t have anything approved specifically for this particular subset of patients.

Since the Soda paper linking the ALK mutation with lung cancer, we have been fortunate to follow the progress of a compound, originally in development as a c-MET inhibitor, crizotinib. Serendipity is a fine thing sometimes, as the agent had weak Met activity, but Pfizer realised that it had potent ALK activity and sensibly switched the development strategy to investigate it’s possible role in targeting ALK in people with lung cancer. This was a smart decision that is now paying off with a raft of promising data coming out this year at the ASCO and ESMO cancer conferences.

The data from ESMO

Data from a phase I trial was reported in Milan last month.  The study consisted of two parts:

  1. A dose-escalation study that enrolled patients with advanced solid tumors (n=37), including NSCLC, colorectal, pancreatic and inflammatory myofibroblastic tumors (IMT), to determine toxicity and the maximum tolerated dose (MTD).
  2. An expansion cohort, where patients with ALK-positive advanced NSCLC (n=113) were prospectively identified and enrolled with a dose of 250mg twice daily (BID), in order to evaluate the safety and activity of crizotinib in this patient population. All patients had received at least one prior chemotherapy regimen.

Let’s focus on part 2 and the lung cancer patients for brevity.  An important point to note is that majority of patients in the analysis had adenocarcinoma histology and were never or former smokers. The progression free survival (PFS) results were particularly impressive.  At the time of the analysis, preliminary median PFS was 9.2 months (95% CI: 7.6, 10.3), with a median follow-up of 8 months.  Nearly half (47.8%) of the patients with NSCLC remain in follow-up for PFS, while 32% of patients experienced disease progression.  Of those who progressed, 42% continued to receive treatment with crizotinib, as they were determined by investigators to be receiving continued clinical benefit.

The side effect profile showed the agent was well tolerated. The most commonly reported adverse events (all grades) included nausea, diarrhea, mild visual disturbances, and vomiting. Grade 3 ALT (alanine aminotransferase) and AST (aspartate aminotransferase) elevations occurred in four patients.  One patient experienced a grade 4 ALT, another had grade 3 pneumonitis and one patient discontinued the study due to treatment-related adverse events.  Neutropenia, lymphopenia and fatigue were also reported at grade 3 severity (n=6). Compared to standard chemotherapy regimens used to treat NSCLC, I think this looks a much more tolerable and acceptable profile so far.

The NEJM data

The NEJM article from Kwak et al., (2010) describes updated results from the part 2 expansion cohort in the phase I trial described above and offers an updated snapshot of the 82 patients reported at ASCO.  The findings (at the data cut-off) were as follows:

  • The main side effect was mild GI symptoms (grade 1 or 2) and grade 3/4 events were similar to those reported at ESMO.
  • The overall response rate was 57%, with a mean of 6.4 months.
  • There was 1 confirmed complete response (CR) and 46 confirmed partial responses (PR). 27 patients (33%) had stable disease.
  • A total of 63 of 82 patients (77%) were continuing to receive crizotinib.
  • The estimated 6 month PFS rate was 72%.

These data illustrate the value in molecular prescreening large numbers of people with NSCLC to determine who should receive the agent.   Interestingly, the ALK mutation was found in approx. 5% of those who underwent screening. It’s unclear from the paper whether any of the patients who were ALK+ also had an EGFR mutation or whether they are mutually exclusive, but if any patients with NSCLC have both, it would interesting to see if a combination with crizotinib and erlotinib would improve survival.

Overall, these results are both very encouraging and promising for a phase I trial.  Certainly, I haven’t been as excited about such early data since the imatinib (Gleevec) phase I data was presented by Brian Druker (OHSU) in 1999.  Crizotinib is certainly something I will be eagerly following as it progresses through R&D and Pfizer should be applauded for their speedy development in clinical trials once the ALK mutation was discovered and published.

The future

Beyond lung cancer, another article in the NEJM described the impact of crizotinib in treating ALK-rearranged inflammatory myofibroblastic tumour (IMT) (see link below).  This is a rare soft tissue sarcoma arising out of mesenchymal cells and characterised by spindle cell proliferation with an inflammatory element.  Butrynski et al., describe a single case report of a patient with a sustained partial response to crizotinib, thereby potentially offering a new therapeutic strategy for treating these patients.

The Japanese researchers have also described mutations that confer resistance to ALK inhibitors.  Choi et al., have now reported the discovery of two secondary mutations (L1196M and C1156Y) within the kinase domain of ELM4-ALK that conferred resistance to treatment in the NEJM (see link below). This is important, as we have learned from the CML experience, because different inhibitors may target different mutations, thereby allowing sequencing and selection of treatment according to the molecular status of each patient.  The parallels between CML and NSCLC in treating a translocation fusion gene are quite striking.  Aside from Pfizer, a number of other companies are also developing ALK inhibitors including Ariad, Chugai/Roche, Infinity and Cephalon.  No doubt others will also follow into the clinic soon, which is great news for patients.

ResearchBlogging.org

Morris, S., Kirstein, M., Valentine, M., Dittmer, K., Shapiro, D., Saltman, D., & Look, A. (1994). Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin’s lymphoma Science, 263 (5151), 1281-1284 DOI: 10.1126/science.8122112

Shiota M, Fujimoto J, Semba T, Satoh H, Yamamoto T, & Mori S (1994). Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene, 9 (6), 1567-74 PMID: 8183550

Soda, M., Choi, Y., Enomoto, M., Takada, S., Yamashita, Y., Ishikawa, S., Fujiwara, S., Watanabe, H., Kurashina, K., Hatanaka, H., Bando, M., Ohno, S., Ishikawa, Y., Aburatani, H., Niki, T., Sohara, Y., Sugiyama, Y., & Mano, H. (2007). Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer Nature, 448 (7153), 561-566 DOI: 10.1038/nature05945

Kwak, E., Bang, Y., Camidge, D., Shaw, A., Solomon, B., Maki, R., Ou, S., Dezube, B., Jänne, P., Costa, D., Varella-Garcia, M., Kim, W., Lynch, T., Fidias, P., Stubbs, H., Engelman, J., Sequist, L., Tan, W., Gandhi, L., Mino-Kenudson, M., Wei, G., Shreeve, S., Ratain, M., Settleman, J., Christensen, J., Haber, D., Wilner, K., Salgia, R., Shapiro, G., Clark, J., & Iafrate, A. (2010). Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer New England Journal of Medicine, 363 (18), 1693-1703 DOI: 10.1056/NEJMoa1006448

Choi, Y., Soda, M., Yamashita, Y., Ueno, T., Takashima, J., Nakajima, T., Yatabe, Y., Takeuchi, K., Hamada, T., Haruta, H., Ishikawa, Y., Kimura, H., Mitsudomi, T., Tanio, Y., & Mano, H. (2010). EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors New England Journal of Medicine, 363 (18), 1734-1739 DOI: 10.1056/NEJMoa1007478

Hallberg, B., & Palmer, R. (2010). Crizotinib — Latest Champion in the Cancer Wars? New England Journal of Medicine, 363 (18), 1760-1762 DOI: 10.1056/NEJMe1010404

Butrynski, J., D’Adamo, D., Hornick, J., Dal Cin, P., Antonescu, C., Jhanwar, S., Ladanyi, M., Capelletti, M., Rodig, S., Ramaiya, N., Kwak, E., Clark, J., Wilner, K., Christensen, J., Jänne, P., Maki, R., Demetri, G., & Shapiro, G. (2010). Crizotinib in ALK-Rearranged Inflammatory Myofibroblastic Tumor. New England Journal of Medicine, 363 (18), 1727-1733 DOI: 10.1056/NEJMoa1007056

2 Comments

A new non-invasive DNA test for colorectal cancer

By on October 29, 2010

The Holy Grail of colorectal cancer prevention – a reliable screening test that users don’t dread and avoid – appears to be getting close.

A novel test that detects telltale DNA markers in stool samples correctly identified 85 percent of colon cancers, 64 percent of significant precancerous polyps, and 90 percent of healthy samples, researchers announced Thursday in Philadelphia at a conference held by the American Association for Cancer Research.

“There is no other noninvasive screening test for colon cancer that comes close” to that accuracy rate, said David Ahlquist, a Mayo Clinic researcher who invented part of the technology and who is working with the commercial developer, Exact Sciences of Madison, Wis.

The DNA test is still experimental, hasn’t been validated under real-life conditions, and will take at least another year of development, he said.

via Researchers at Philadelphia conference announce progress toward noninvasive colon cancer test | Philadelphia Inquirer | 10/29/2010.

This was a most interesting new test in development that was covered here at the AACR colorectal cancer biology to therapy meeting in the press briefing yesterday.

Current methods of colorectal cancer (CRC) screening for people over 50 involve either colonoscopy, which is invasive, or virtual colonoscopy, which is not covered extensively by insurers.  Both require a not inconsiderate amount of time to do, not to mention the inevitable nervousness that goes with such procedures.  Routine fecal tests currently available have unfortunately been shown to miss most advanced pre-cancers, so there is an real opportunity to develop a more sensitive and useful detection approach.

This new test takes a stool sample and looks for markers that indicate early presence of adenomas in the colon in a small validation study (n=59) by testing people who were being evaluated for CRC by colonoscopy, in other words, they had a high risk for CRC or were strongly suspected of having cancer. Such well characterised patients allows for quick segmentation into normal and cancerous groups, rather than waiting for long term epidemiology follow-up to see who develops cancer or not, which can take years.

According to the Mayo Clinic scientists, several combinations of methylation markers based on tissue DNA were found that discriminate colorectal neoplasia from normal mucosa.  These were evaluated as part of the test validation process.  The markers that were found to be useful included 3 methylated genes (TPFI2, BMP3, NDRG4), plus human DNA.

A huge advantage of this simpler approach is that I can see that potentially, primary care doctors could order it as part of routine screening at an annual physical, thereby finding colon adenomas early rather than waiting for a carcinoma to develop later in life.

The test from Exact Sciences looks at 4 genes known to be associated with the development of colorectal cancer and appears to be able to detect them with 85% sensitivity.  Another DNA test is also being developed in Germany by Epigenomics AG, but differs in that it uses blood samples and looks at changes in Septin 9, which is not used in the Exact Sciences test.  It is currently available to physicians in Germany.

The development of non-invasive easy to use tests like these is important because we all know that the earlier we detect abnormal growth, the easier it is to cure and improve overall outcomes for any cancer, as Bert Vogelstein emphasised in his talk the other evening and Tyler Jacks did in his keynote at the Xconomy meeting in Boston the other week.  Colon cancer, for example, has a 90% cure rate when detected and treated early with surgery.

The lead investigator, Dr David Ahlquist, told me that the Mayo clinical studies with the Exact Sciences test are due to run until the end of 2012, so if all goes well we may see an approved validated test for wide scale testing available by 2013.  Certainly the timeline is looking like the next couple of years rather than a much longer timeframe, which is very encouraging to all of us who have lost family members to the disease.  While a better screening test won’t bring them back, it does offer hope that we may be able to avoid losing other people to the disease because their cancer was detected too late to do anything about it.

The pace and new advances in the early detection of cancer is something we can all be cheered about.  Long may the trend continue!

5 Comments

The cancer genome

By on October 28, 2010

Last night at the AACR keynote session at Colorectal cancer: biology to Therapy, I listened to Bert Vogelstein’s talk on the cancer genome as applied to colorectal cancer.   It was a deja vu moment of sorts, as I started my current Moleskine at AACR earlier this year with keynotes from Charles Sawyers and Bert Vogelstein. It therefore seemed most apt to finish the current volume of science notes with another talk from the same person at another AACR meeting.

The other good thing about the talk for me is that I have a few circles around squiggles from my original notes – it was good to finally figure out what the chicken scratch was trying to tell me! You can see how bad the notes were from my iPhone shot at the time; it must happen to all of us at some point – hastily scribbled notes while listening and writing in one’s lap is a recipe for disaster 🙂

Now, I’m not going to repeat Vogelstein’s talk as you can read that from the link to the April Keynote, but what interested me most about this one is that he expanded the application of what we’ve learned from the biology to patients.  This is really important, because science is ultimately about truth and how that can be applied to improving things.

Vogelstein identified three key areas that he felt had most implications for cancer patients:

  1. Cancer predisposition
  2. Identifying important biomarkers for following people with cancer
  3. Improved methods of detection

The third point is particularly relevant as it was also something Tyler Jacks talked about at the recent Xconomy meeting in Boston.  Solid tumour cancers such as colorectal cancer can take 25-30 years to develop into a metastatic carcinoma, so finding ways to identify the mass much earlier will be critical to better treatments in the future.

Future Challenges

Vogelstein expanded his ideas into some key points for future research:

  1. Improved understanding of the pathways
  2. Development of novel therapies targeting the pathways
  3. Better early detection methods

Overall, it is clear that we have come a long way over the last decade, but there is still a lot of work to do but this task will be made much easier by a larger wealth of knowledge than we started out with.

3 Comments

AACR Colorectal Cancer Meeting: Biology to Therapy

By on October 27, 2010

Later today I’m heading off to Philadelphia to attend a special conference at the American Society of Cancer Research (AACR) meeting on colorectal cancer entitled Biology to Therapy.  There’s still time to pack a back and head on down as the main meeting doesn’t start until tomorrow.

Tonight, I’m very much looking forward to the Keynote from Prof Bert Vogelstein (Johns Hopkins) who is doing a talk entitled:

“Colorectal cancer genomes and their implications for basic and applied research.”

You can check out the full program here.

Over the next couple of days I’ll post some blogs on a few topics of interest from the sessions – watch this space for more.

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What’s the best treatment for elderly patients with untreated multiple myeloma?

By on October 26, 2010

It’s a while since I’ve written about multiple myeloma, but after this interesting paper popped up in The Lancet Oncology, I couldn’t resist.

Many cancers occur more frequently in the elderly, a testament to the extended lifestyle many of us now enjoy compared to ancient times.  This offers many challenges compared to treating younger fitter people, not least are performance status and managing toxicities.

A standard induction treatment in untreated multiple myeloma is now the combination of bortezomib (Velcade), melphalan and prednisone (VMP), which has been shown to be superior to MP alone.  In elderly people with multiple myeloma, however, the side effects can be difficult to tolerate.

A Spanish group has considered this challenge and investigated whether a different regimen would be as effective but less intensive, thereby offering an alternative option for elderly multiple myeloma patients.

What they did was really interesting. The used bortezomib, thalidomide and prednisone (VTP) as induction therapy compared with the standard VMP followed by maintenance treatment with either bortezomib and thalidomide (VT) or bortezomib and prednisone (VP).

Here’s the treatment schedule:

The efficacy results were encouraging:

Induction:            VMP      VTP

PR                       81%     80%

CR                       28%     20%

Maintenance:         BT        BP

CR                        44%    39%

What about the side effect profile?

Overall, there was less neutropenia and thrombocytopenia in the VTP group (good news), but slightly increased cardiac events. It is also interesting to note that peripheral neuropathy (hand and foot syndrome), one of the side effects of bortezomib treatment had a relatively low incidence (less than 10%) in both groups.

Overall survival was, however, superior in the VMP group (34 months) compared with the VTP group (25 months).

As always, it is ultimately a delicate balancing act between efficacy, survival and side effects, depending of the patient’s treatment goals. The authors reasonably concluded:

“Reduced-intensity induction with a bortezomib-based regimen, followed by maintenance, is a safe and effective treatment for elderly patients with multiple myeloma.”

ResearchBlogging.org
Mateos MV, Oriol A, Martínez-López J, Gutiérrez N, Teruel AI, de Paz R, García-Laraña J, Bengoechea E, Martín A, Mediavilla JD, Palomera L, de Arriba F, González Y, Hernández JM, Sureda A, Bello JL, Bargay J, Peñalver FJ, Ribera JM, Martín-Mateos ML, García-Sanz R, Cibeira MT, Ramos ML, Vidriales MB, Paiva B, Montalbán MA, Lahuerta JJ, Bladé J, & Miguel JF (2010). Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myelom The lancet oncology, 11 (10), 934-41 PMID: 20739218

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Pharma Strategy Blog is now live and kicking again

By on October 25, 2010

As promised, over the weekend we changed hosts and this blog is now live in it’s new home.  We hope you like the new look and feel, which will continue to improve over time.

The archives and categories on the right will help you find old posts via a drop down menu or you can use the Search button under the Contact Us icons in the top right.  Some new tools have been added, such as the little E-mail icon, also on the top right.  Please do keep your suggestions for new posts and discussion ideas coming, they are much appreciated and I do try to act on them whenever possible.

We will be adding a short occasional newsletter service after conferences, which you will be able to sign up for in the Newsletter section at the top – it isn’t live yet, but we’ll be adding a means to add your E-mail for subscriptions very soon.  Those who are current blog subscribers will also need to sign up as we respect your privacy and won’t be assuming that everyone is interested!

For those of you who bookmarked the blog in your browser it should still work, but the RSS feed has changed and you may need to check that it still works.  To ensure you don’t miss your daily dose of Pharma Strategy Blog you can subscribe easily by clicking here.

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Pharma Strategy Blog is moving!

By on October 22, 2010

Recently, the limitations of the current blogging platform have become apparent when we started to consider the idea of adding some new features to the blog such as podcasts, video interviews, newsletters etc. A number of readers have also requested more extensive downloadable reports for purchase, so this is something we will be able to do in the near future through a more secure site.

The time has now come to move to a new platform.

This weekend we plan on making the transfer after practising with two other blogs, so Pharma Strategy Blog will take it's turn and will be down temporarily while we make the hosting changes.

Hopefully, it will be business as usual on Monday morning using the same url with no technical glitches!

We apologise in advance for any downtime on Sat and Sun, but see y'all on the other (brighter) side after the weekend!

6 Comments

Boston's War on Cancer – Xconomy meeting

By on October 21, 2010

Yesterday, I attended an Xconomy meeting hosted by Millennium on the war on cancer.  It was an interesting meeting, well attended and with some spirited interaction between the presenters, panels and audience.

180497316For those unaware of the Boston scene, MIT sits by the Charles River and several biotech and pharma companies including Millennium, Ariad, sanofi-aventis, Genzyme and Novartis Institute for Biomedical Research (NIBR) sit behind it.  You can walk between them in minutes. Mass General and Tufts Hospitals are just 5-10 mins away in a taxi on the Boston side of the river, Harvard is a few minutes by cab from MIT in Cambridge.

It’s the very ease of relative access that makes interactions here much easier and also valuable. Last time I was here, I kept bumping into people I knew, including researchers in the streets, “Oh, can I ask you a quick question please?!”

It’s the classic Porter cluster effect and it seems to be working well here.  Still, you never see this in NJ Pharma-land, ever. Why? Because they all live on ivory tower campuses that you usually have to drive around and academia is miles away in Manhattan (and Boston). I hadn’t really thought of it this way before, but I can see that new emerging transformative technologies and therapies are more likely to come out of Boston and San Francisco than New Jersey, at least in the cancer field.

There were a number interesting observations that emerged from the meeting.

  1. No pharma peeps hiding behind a lectern here – people, including Millennium CEO Deborah Dunsire, stood out in front and engaged with the audience or became animated in panel discussion.  This is refreshing and I’d love to see more of this more laid back approach, without spin and carefully couched speeches.
  2. The panel session with Alexis Borisy (CEO Foundation Medicine), Tuan Na-Ngoc (CEO Aveo Pharma), Adelene Perkins (CEO Infinity), Nancy Simonian (CMO Millennium) was fun and adroitly moderated by Sylvia Westphal (Xconomy). Biomarkers, selecting patients carefully for treatment, targeted therapies, new combinations, new smarter scientific approaches, and greater collaborations in research with academia were very much the main topics discussed.
  3. While the authorities seem to be trying to build walls between industry and academia, the prevailing mood was very much that this is a bad thing and that closer collaborations should be both welcomed and encouraged.  We can’t continue with the old style models of development and expect them to work well in the new environment. Such an approach, with its high costs, low success rate and high phase III attrition, is not sustainable in the long run.
  4. As we learn more about the biology of cancer, so we should become smarter about which drugs we evaluate in which patient subsets, which combinations and sequences, in earlier rather than later disease.  Everyone wants to see bigger wins, not incremental improvements.
  5. Some interesting new emerging technologies were discussed were discussed on RNAi by Dave Okrongly from Quanterix and epigenetics by Mark Goldsmith of Constellation Pharma. The single molecule testing concept particularly caught my imagination. Quanterix’s PSA assay test appears to be 1000x more sensitive than current assays and this has major implications for the detection and monitoring of prostate cancer. Why? Because if we can pick up aggressive disease (where the PSA rate doubles) earlier, we may ultimately be able to do better with earlier and more appropriate intervention treatment for the patients before the disease metastases out of control.
  6. The mood in Boston seems much more cohesive, upbeat and focused than what I see in the NY/NJ region dominated by big Pharma and old school ways of thinking.
  7. It’s all about the science, baby!

One of the highlights for me, other than the excellent networking opportunities, was the final panel session with Mike Huckman (formerly Pharma’s Market on CNBC now on the dark side at MSL, a PR agency) and Tyler Jacks, a cancer researcher from MIT/Koch Institute.

Mike kicked off by asking Tyler about the Cancer Caucus event hosted by Harold Varmus of the NCI a couple of weeks ago, where a key group of scientists and clinicians were holed up discussing and identifying the most important areas in cancer that we don’t know about or need addressing.  Tyler identified his 3 key things as:

  1. Identifying phenotypes and drivers of cancer that link to molecular aberrations
  2. Making sense of the complexity of the human genome (we have a lot of data but what does it all mean?)
  3. Figuring out the characteristics of early lesions and how they progress (if we figure that out, can we stop them sooner?)

The NCI meeting created a mechanism for discussion and dialogue, but closer collaboration (between industry and academia) is clearly seen as the way forward.

Jacks also discussed a number of other pertinent areas, including advances in preclinical models and how new generation versions are much more accurate and sensitive for predicting what might happen. The old models were largely ‘short cuts’ and not very representative of what’s going on. The new models and approaches are teaching us more about resistance and how it arises, for example.

Related to this is better diagnostic tests, leading to better more targeted treatments. Interestingly, he was very upbeat about solving the cancer problem and how the next generation of researchers will likely see bigger strides as we start unravelling the puzzles.

Mike also asked Tyler about Boston as a location for fighting the war on cancer. Tyler replied that it is a wonderful environment for this given that acedemia, biologists, engineers and biotech research all exist in the same place, with MIT providing a natural hub or link. The culture of MIT was discussed as something they are working hard on, although younger scientists are inevitably more willing and flexible to change and adapt (this also applies anywhere).

For the next week or so, the Twitter stream will still be searchable, so for those interested, you can check my live tweets from the meeting using #xconomy and get a flavour for what the biotech chiefs and academia think about ‘Boston’s War on Cancer’ – remember to read from the bottom up as the newest tweets will be at the top.

Unfortunately, Twitter did it’s famous fail whale (no access) near the end (grrr) and thus the last two sessions are missing, including the chat with Tyler Jacks.

If you were at the Xconomy meeting, do feel free to add anything I’ve missed or if you have any other thoughts on the sessions. For me, it was a great afternoon and I’d to thank Luke Timmerman of Xconomy for inviting me to the excellent event, highly recommended, would definitely go again!

5 Comments

What's in Placebos: Who knows? Analysis of randomized, controlled trials

By on October 19, 2010

Background: No regulations govern placebo composition. The composition of placebos can influence trial outcomes and merits reporting.

Purpose: To assess how often investigators specify the composition of placebos in randomized, placebo-controlled trials.

Data Sources: 4 English-language general and internal medicine journals with high impact factors.

Study Selection: 3 reviewers screened titles and abstracts of the journals to identify randomized, placebo-controlled trials published from January 2008 to December 2009.

Data Extraction: Reviewers independently abstracted data from the introduction and methods sections of identified articles, recording treatment type (pill, injection, or other) and whether placebo composition was stated. Discrepancies were resolved by consensus.

Data Synthesis: Most studies did not disclose the composition of the study placebo. Disclosure was less common for pills than for injections and other treatments (8.2% vs. 26.7%; P = 0.002).

Limitation: Journals with high impact factors may not be representative.

Conclusion: Placebos were seldom described in randomized, controlled trials of pills or capsules. Because the nature of the placebo can influence trial outcomes, placebo formulation should be disclosed in reports of placebo-controlled trials.

via www.annals.org

 

Thanks to Bruce Lehr of the Big Red Biotech Blog for bringing this topic to my attention.

Pills11In many trials of new drugs in development such as cardiovascular, dermatology, neuroscience etc, the test agent is typically compared to a placebo with a similar formulation such as a pill, topical cream etc, but as the journal points out, rarely is the composition defined in detail. 

This is not surprising, as the authors of the paper reported that they found that only a paltry 8.2% of the 86 studies they looked at actually stated clearly what the contents of the placebo were.

Does it matter?

Well, you might think it's just a 'sugar pill', but as this article in the LA Times noted, some placebos in cardiovascular trials might consist of olive oil or other polyunsaturated oils, thereby potentially reducing cholesterol and heart disease. Certainly something to think about, as they may have unexpected effects.

Although most cancer clinical trials are typically comparing a new treatment to the standard of care, often placebo is used in the comparator combination. A recent example is the abiraterone trial reported last week at ESMO in men with advanced, castration resistant prostate cancer after prior docetaxel therapy. The study compared abiraterone (a pill) with prednisone (a steroid) to placebo (pill) plus prednisone. Based on the information provided in clinicaltrials.gov, it isn't clear what the placebo actually was.

I liked the quote from the authors in the LA Times article above:

"Perfect placebo is not the aim, rather, we seek to ensure that its composition is disclosed."

Given the placebo could have unexpected effects or at least have an impact, perhaps we should start disclosing what's actually in them.


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