Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts by MaverickNY

An overview of Roche's oncology pipeline

By on March 26, 2010

At last weeks investor meeting held by Roche in downtown Wall Street, the Board reviewed the pipeline opportunities in a number of areas.  Earlier this week I wrote about the non-oncology pipeline and today will form an overview of the cancer drugs in development.

One of the things that Roche is renowned for is life cycle management.  They do this better than many in the industry in my opinion and it makes an enormous difference not only to continuity, but also long term revenues and performance. Too many companies take a short term view and do not think ahead to the future. This is a big mistake. Perhaps they get bogged down in classic silos or management do not see it as a priority, but it does make a difference. 

Why?

Well, for starters, think about the basics of marketing. It is much easier to sell new products to existing customers than it is to sell existing products to new customers and even harder to sell new products to completely new customers.  

Thus life cycle management is a smart strategy and done well, enhances the experience for everyone involved whether employees or investors.  I only wish more companies paid closer attention to this important aspect of Pharma marketing.

The other thing I like about Roche's approach to R&D is rigorous and strong proof of concept studies (usually in phase II). Between Roche and Genentech, they both do this particularly well in oncology, it seems to be their signature. This partly explains why they mostly end up with a continuous wall of data across several products including trastuzumab (Herceptin), rituximab (Rituxan) and bevacizumab (Avastin). Of course, negative trials do occur but overall, they seem to have more positive trials than not. This partly explains why they have fewer phase III flops than say, Pfizer, because they spend the time in phase II working things out rather than rushing aggressively ahead on the basis of early evidence.

So what did we learn from the pipeline presentations last week?

There are late stage oncology products in development that look promising.

One example is trastuzumab-DM1, which is basically modified Herceptin with a potent cell killing agent, DM1, bolted on. The goal is to improve the action of Herceptin in metastatic breast cancer, and at the same time invetigate whether the xenograft data in a variety of cancers (breast, ovarian, lymphoma and prostate) with an armed antibody is an effective strategy in people. Recent phase II data from the San Antonio Breast Cancer Symposium in heavily treated women with metastatic breast cancer look encouraging. Phase III trials have already begun and if all goes well, filing is currently anticipated by 2012.

Also potentially strengthening the breast cancer franchise is pertuzumab, a monoclonal antibody that targets HER2. Early phase I trials in several cancer types produced so-so results, but more recent phase II data in breast (combined with Herceptin) and ovarian cancer (in combination with gemcitabine) published this month in JCO look interesting.

Perhaps the most exciting compound though, is PLX4032/RG7204, a BRAF inhibitor being evaluated in malignant melanoma. Currently available data suggests survival is improved by 6 months so the big question is what causes resistance to develop and how this can be overcome. Data on this compound is expected at ASCO, where many are keen to see how it stacks up with ipilimumab (BMS).

In hematologic malignancies, GA101 or galiximab is being evaluated in non-Hodgkin's Lymphoma (NHL) and chronic lymphocytic leukemia (CLL). It appears to target a different part of the CD20 isotope than rituximab and this may increase it's efficacy. Phase III trials began in 4Q09 thus it will be a little while before we see some results. There is clearly an unmet medical need in the 3rd line refractory disease for more tolerable agents and rituximab is very much the bedrock of treatment for both across multiple lines of therapy either alone or in combination with chemotherapy. A similar agent will likely have good take up with the right approach.

Genentech are investigating various new and improved approaches to angiogenesis, but these are in much earlier development and the bar is very high with bevacizumab (Avastin), even for the company who manufacture it. The list of anti-angiogenesis compounds that didn't make it to market is very long indeed.

I've left the best to last, as hedgehog (Hh) signalling is one of my favourite pathways – it always reminds me of the cheerful cartoon character, Sonic the Hedgehog. RG3616, licensed from Curis, is currently in phase II trials for advanced basal cell carcinoma and trials are also underway for medulloblastoma. If interested, you can find out more about the pathway and the science here.

Overall, the oncology pipeline has a nice mix of follow on compounds to strengthen life cycle management with a raft of monoclonal antibodies with different targets in new cancer types.  Such a strategy should reduce risk and drive the future bottom line if the promise delivers in phase III trials.

ResearchBlogging.org

Baselga, J., Gelmon, K., Verma, S., Wardley, A., Conte, P., Miles, D., Bianchi, G., Cortes, J., McNally, V., Ross, G., Fumoleau, P., & Gianni, L. (2010). Phase II Trial of Pertuzumab and Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer That Progressed During Prior Trastuzumab Therapy Journal of Clinical Oncology, 28 (7), 1138-1144 DOI: 10.1200/JCO.2009.24.2024

Makhija, S., Amler, L., Glenn, D., Ueland, F., Gold, M., Dizon, D., Paton, V., Lin, C., Januario, T., Ng, K., Strauss, A., Kelsey, S., Sliwkowski, M., & Matulonis, U. (2009). Clinical Activity of Gemcitabine Plus Pertuzumab in Platinum-Resistant Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Journal of Clinical Oncology, 28 (7), 1215-1223 DOI: 10.1200/JCO.2009.22.3354

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Healthcare reform: comparative effectiveness may be here to stay in the US

By on March 25, 2010

"The latest beneficiary of healthcare reform to step into the spotlight: Comparative effectiveness. The bill signed by President Obama earlier this week sets up a new institute for head-to-head studies of drugs and devices–and arms it with a $500 million annual budget. That positively dwarfs the $1.1 billion in comparative-effectiveness funding approved by Congress last year."

Source: Fierce Pharma


What's interesting to me about the Obama health care reform law is that tucked away on page 1617 out of 2400 is a measure discussing comparative effectiveness (hat tip to Bloomberg for spotting it).  In the short run, the measure won't have much impact, but in the long run, say by 2013 onwards it will start to bite.

This is where savings will start to be made, so if for example, a branded drug doesn't appear to offer much benefit over a generic, then undoubtedly the payers will force dispensing of the generic version and save significant expense in the process.

One thing I had forgotten until sitting through the non-oncology presentations at the recent Roche IR meeting is that most trials compare the new drug to placebo rather than standard comparators, so it will be difficult to compare drug performance in a given class without head to head trials.  Of course, in many cases, they are similar and success may well be determined by either being first to market by several years or by creative marketing and positioning.

In oncology, it is more typical to either compare a new regimen to the established standard of care or to add an experimental agent to the standard of care and then compare to the standard alone.  In this way, a sense can be gained regarding how well the new drug fits in the existing treatment algorithm.  

Thus drugs that do not show significant improvement to the standard of care generally are terminated in that indication or fail to get approval. Brutal perhaps, but it is an effective way to sort the wheat from the chaff.  The only time placebos typically appear in oncology trials is in refractory disease where there are no available comparators, so a drug is compared to placebo or best supportive care.

A world apart in drug development.

So what of the future?  According to Bloomberg:

"The new legislation creates a nonprofit Patient-Centered Outcomes Research Institute and tasks it with setting a national agenda for the studies, as well as providing more money and disseminating results."

It's going to be an interesting ride for sure and of course, other countries already have comparative effective research built into the approval process, as the UK already does.  Ultimately, resources become limited, so it's a choice between having your health care managed by the limitations of the hospital budget (UK) or limited by your ability to pay (US).  Either way, choices and options are always rationed to some degree.

One question I'm wondering about is how well prepared are Pharma and Biotech?  The big companies are already doing CE research, the little guys?  Maybe not so much.

Are you incorporating comparative effectiveness into your strategic and life cycle management plans?

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Merck KGaA reviewing cardiac data for Erbitux in lung cancer trials

By on March 25, 2010

"Merck KGaA is reviewing heart risks of its tumor-fighting Erbitux drug in several types of cancer after European regulators asked for more information on the treatment’s safety. 

The European Medicines Agency requested the review after rejecting Erbitux for use in lung cancer patients, according to a report published online on March 12. The drug regulator identified an “increased incidence of cardiac events” in lung cancer patients age 65 years or more, in particular high-risk patients with a history of heart problems."

Source: Bloomberg

This was an interesting snippet of news that I saw in the mass of alerts this morning, and no obvious press release from any of the companies involved with the drug, Merck KGaA (in Europe), BMS or Imclone (US partners).  

Part of the problem here is that many people with lung cancer also tend to have cardiac co-morbidities and thus the two may go hand in hand. To be fair, similar side effects have not apparently been reported in other cancers, such as colon cancer.

If the analysis reveals negative findings, then it may lead to changes in the prescribing information, which will not be good news.  Of course, the company are hopeful that will not happen, because changes in the EU labelling for Erbitux (cetuximab) may subsequently impact the US one too.  

Merck are already having a rough week on the issues management and communications front with the suspension of the Stimuvax trials after a patient being treated with the vaccine developed encephalitis. At least the current issue didn't get reported on a Friday!

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Thoughts on the Roche non-oncology pipeline

By on March 24, 2010

Last Thursday, I attended the Roche Investor meeting in Wall Street, live-tweeted it using the hashtag #RocheIR and enjoyed an interesting event packed full with lots of information to digest.  

Photo-6Luckily, I bumped into an old colleague from Sandoz UK days and was delighted to learn that he is now Global Head of Regulatory at Roche.  Of course, if you spend a day out of the office, you pay for it severely the next day with an even bigger pile of emails, client requests, RFPs and telecons to catch up on >.<

In fact, I was so busy, I didn't have time to post a blog about Thursdays event on Friday, but I did manage to interview Dr. Laura Esserman, the breast cancer surgeon at UCSF behind the fascinating I-SPY2 project that we discussed last week. More on that tomorrow.

The next two days of blogs will cover two reports on the Roche pipeline (non-oncology and oncology) and Dr. Esserman's unique perspective on getting the I-SPY2 project up and running, she has certainly made a difference shaking things up and challenging people's approach to drug development in a short space of time. 

Let's begin with the non-oncology agents in Roche's pipeline.

Granted I normally write more about oncology, hematology and immunology here, but my background in Pharma started in more humble beginnings as a sales rep in the statin market, where we were also looking to differentiate ourselves by being an attractive option for people with diabetes, who have a much higher risk from long term CV mortality.  

I was therefore very interested to see where Roche were going with this approach fifteen years later because we never had much success with it, despite Marketing thinking it looked to be an attractive opportunity no one was exploring.  However, the undoubted long risk of earlier mortality and morbidity is subsumed to more urgent and immediate needs such as getting sugar levels under control and insulin levels regulated.  Adding yet another drug into the mix complicates things for physicians considerably. Plus taking oral drugs over time also results in long term compliance issues, which may impact outcomes negatively.

Dalcetrapib is being developed for dyslipidemia and cardiovascular high risk patients. The first trial looks at artherosclerotic disease progression, lipid profile and biomarker profile and long-term safety profile of dalcetrapib in people with established coronary artery disease compared to placebo. 

The primary endpoints include:

  • Nominal change from baseline to study end in coronary percent atheroma volume (PAV) of the target coronary artery assessed by IVUS.
  • Rate of change from baseline to study end in carotid intima-media thickness (CIMT) using B-mode ultrasound


The second trial is looking at the potential of dalcetrapib to reduce cardiovascular morbidity and mortality in stable coronary heart disease patients with recent Acute Coronary Syndrome (ACS) and evaluate the long term safety profile of the drug, again, compared to placebo. 

The primary endpoint is defined as:

  • Time to first occurrence of any component of the composite cardiovascular event (cardiovascular mortality and morbidity)


These two phase III trials are currently recruiting people with coronary artery disease, so we won't know the results for quite a while, probably over the next 2-3 years.  Such large scale trials are very expensive and time consuming to conduct.  For all the the noise about statins reducing cholesterol, I sometimes wonder what impact they actually have on long term mortality and morbidity. Do they lead to any meaningful clinical change in outcomes, ie improved survival, rather than just lowering cholesterol per se?

Roche also have two drugs in development for type II diabetes, both of which are tongue twisters: taspoglutide, a new GLP-1 drug for Type 2 diabetes, and aleglitazar, for cardiovascular high risk in diabetes. The diabetes market is suddenly getting very crowded with numerous insulin, syringes, pens, pumps, and oral therapies all available. 

Thus as a marketer, I'm wondering how new products into these segments differentiate themselves from existing therapies in this competitive disease?  It's one thing to claim blockbuster potential, but quite another to capture the heart and minds of the physicians prescribing yet another me-too in a crowded existing market segment.  

The $64M blockbuster question in diabetes for BMS's Onglyza, in the DPP-4 segment, rapidly turned into a spectacular $4M flop in the launch year. The inhaled insulins such as those from Pfizer and Mannkind were either withdrawn or struggle to make it to market. Two precautionary tales of humility in the diabetes market if there ever were some.

How Roche develop and differentiate taspoglutide and aleglitazar from existing segment leaders will therefore be an interesting process to watch.  For now, we can sit back and wait for the various clinical trials to complete and see how the agents stack up.  The phase III trials were initiated for aleglitazar were initiated in 1Q10, taspoglutide initial phase III results were released in 4Q09 and further results are expected in 2010. The results for dalcetrapib will not be available for a few years given the enrollment is just starting.

Two other non-oncology drugs in development include RG1678, a GLY-T1 inhibitor, for treatment of the negative symptoms of schizophrenia. The initial phase II results were positive last year and phase III trials are planned for 2010.  

Ocrelizumab is a humanised CD20 monoclonal antibody similar to rituximab. The phase III trials were negative in rheumatoid arthritis and lupus, despite the agent being developed to reduce the development of drug neutralizing antibodies and infusion reactions. Recent studies, however, established that the safety risk associated with ocrelizumab outweighed the benefits and Roche disclosed that several patients died from infections so the development in RA and lupus was promptly suspended. Meanwhile, ocrelizumab is also being developed for the treatment of people with multiple sclerosis and a Go/No Go decision for the phase III development is expected this year.

Given the focus on five main disease areas including oncology, virology, immunology, metabolism and CNS, it is good to see new agents being developed in the metabolism and CNS areas after the long term focus on oncology with Genentech lately.  How well they will do in the long run compared to the oncology pipeline, only time will tell.

ChemGenex will need a validated T315i mutation test for omacetaxine in CML

By on March 23, 2010

Yesterday afternoon, the FDA and ODAC met for a second time in the day to review the application for omacetaxine from ChemGenix.  The drug was tested in limited trials in people with chronic myeloid leukemia (CML) for whom tyrosine kinase (TKI) therapy with drugs such as imatinib, dasatinib or nilotinib had failed or who had the T315i mutation.

My previous analysis from last month is here.  Unlike the concerns in the morning with safety and efficacy associated with pixantrone in NHL, this time the FDA were clearly concerned about the validity of commercially available assays to detect the T315i mutation.

I did a search to see what was out there for testing T315i and found two:

  • Quest Diagnostics are advertising one here.
  • DxS Diagnostics are advertising one here.

Interestingly, the DxS one clearly states that it is for research purposes only, not for diagnosis.  I'm not sure if the Quest test has been approved commercially, but it would seem odd of the FDA to make a song and dance about a widely available test if there is one available, so it is possible that both are only available for research purposes so far and as such, not approved for commercial use.  Or it may be that the Quest one is approved but has not yet been validated with omacetaxine.  It isn't overly clear from the information we have so far.

Either way, Kerri Wachter was on the scene at the meeting and tweeted the vote succinctly:

Picture 40
This isn't really surprising: if you are claiming to target a particular marker or target, then you need a validated companion diagnostic test to be commercially available once the drug is approved.  I think what the FDA is saying to ChemGenex is that they need to do a small study comparing and validating the data between commercial assays and the ones used more commonly in hospital Path labs for research purposes and clinical trials.  It's not a big deal, but it does need to be done.

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Thoughts on the pixantrone FDA ODAC meeting

By on March 23, 2010

Yesterday was quite day, with one thing and another.  For starters, the FDA ODAC committee finally held a session for Cell Therapeutics pixantrone in 3rd line NHL and ChemGenenex's omacetaxine, for people with the T315i mutation in CML.  The previously scheduled meeting was cancelled due to the Snowpocalyse that hit DC last month. 

I had to dash off to a doctor's appointment myself so missed most of the action on Twitter and rushed back to catch up at lunchtime by checking Twitter buddies such as Kerri Wachter who was live tweeting from the meeting and Adam Feuerstein of The Street's excellent live blog.

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

You can see my original review of the February FDA documents here.  Sadly, the analysis turned out to be accurate and Adam had noted:

"That was brutal."

Approximately 20 minutes into Richard Pazdur's opening introduction. 

In particular, the FDA felt that:

"Pixantrone has demonstrated evidence of biologic activity, but the mere demonstration of biologic activity is not sufficient for approval."

Ouch!  At that point it becomes incumbent upon the company presenters to argue persuasively to the nine panel members to convince them otherwise.  However, that was going to be a tall order given the FDA concerns regarding:

  1. Neutropenia and infections were higher in pixantrone than the control
  2. Cardiac toxicity was higher in pixantrone than control, including heart failure and ejection fraction

As highlighted in the original analysis of the pixantrone filing, the FDA were also unhappy about the shortened study given only 140 people were enrolled out of the planned 320, leading them to conclude:

  1. Study was not well executed or complete.
  2. Study was inconsistent (only 8 people enrolled in the US and none had a complete response).
  3. Trial did not demonstrate statistical significance or robust findings.

What was weird about the proceedings though, was a clear disconnect between the two parties, as Adam Feuerstein reported live via the webcast:

"Pazdur: FDA not consulted about halting enrollment in trial, not pre-specified in study's statistical plan."

"Bianco: In March 2008 after 140th patient was enrolled, study was closed to enrollment. We consulted with FDA about this."

Checking my Twitter stream, Kerri reported:

Picture 36
Personally, I was surprised that CTI thought that the statistical parameters would not change if they only recruited 140 of the 320 people expected and could proceed on that basis.  This is basic college level statistics – if you majorly change one input, the outliers must also be adjusted.  For this reason, the FDA's decision to treat the data as if an interim analysis had been done is fair and reasonable.

Going forward, it is likely that either all 320 patients would need to be enrolled in a study to meet the minimum FDA requirements or new studies in combination with other agents would be needed.  This latter approach is probably more likely, because the US sites (28 of them) only enrolled 8 people because the preferred treatment in the 3rd line refractory setting is combination chemotherapy, not single agent therapy. 

Perhaps the snowpocalypse last month was a portend of what was to happen.  Either way, yesterday was a bad day in DC for CTIC.

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Bench to Bedside: How can we speed up cancer drugs to the clinic?

By on March 18, 2010

After yesterday's post about the I-SPY trials in neoadjuvant therapy for breast cancer and how they may speed up the process of bringing new innovative cancer drugs to the clinic faster, I was reflecting on my own experiences with imatinib (Gleevec).   

The Philadelphia Chromosome was first identified in 1960 by Nowell and Hungerford. Gleevec was finally approved by the FDA in May 2001, 41 years later.   

Between 1999, when I arrived in the US and working in New Product Development at Novartis until 2001 when Gleevec was launched, I attended scientific meetings including AACR, ASH and ASCO. Often, Dr Judah Folkman, a scientific researcher from Harvard, would talk about angiogenesis and hypothesised that was the principal mechanism by which tumours grew. I listened to his ideas many times because I was curious and found the concept both fascinating and intuitive. There was a long line of drugs that failed to work though, and every meeting seemed to bring yet more negative results.

Now, Folkman first advanced the angiogenesis theory in 1971 in the New England Journal of Medicine, but it wasn't until 2002, when bevacizumab (Avastin), a VEGF inhibitor that prevented angiogenesis from happening, was finally approved for the treatment of colon cancer.   At that point you go, 'oh wow' and realise that Folkman's theory was indeed proven correct.

Thus a tale of two incredible cancer drugs that both took a relatively long time to evolve from scientific idea to effective treatment in people with cancer.  Or perhaps they were actually relatively 'quick' compared to others, but why it takes this long is something we can surely do better at. 

Last night I was researching ideas for drug development and innovation since the concept of bench to bedside fascinates me and came across this enlightening video from a lunchtime talk that Dr Susan Desmond-Hellmann gave last year at UCSF. Oddly, she seems to have trodden similar thought processes and asked why and how can we speed things up as well. 

The short lecture is well worth listening to for those interested in drug development – the good doctor explains the bench to bedside concept far better than I: 

Sources for scholars and clinical scientists:

The NEJM doesn't appear to go back beyond 1993 online, but the original reference to Folkman's article is at: 

Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med 1971;285:1182-1186.

A more recent one from 1995, which provides an update is available online at: NEJM

The future of Oncology

A short while ago on this blog we began a series on Making a Difference about people in the cancer field who have a real passion and excitement for lasting and impactful change. The first one was an interview with Alain Moussy of AB Science in Paris.

image from news.ucsf.edu Today, I had the pleasure of chatting with the admirable Dr. Susan Desmond-Hellmann, formerly Head of R&D at Genentech and now Chancellor at UCSF. It’s a strange business sometimes as we were both working in industry at the same time on different targeted cancer drugs in liquid and solid tumours but our paths never crossed, although it seems we share similar views on cancer drug development, ie purer targeted agents and finding faster ways to market for effective therapies that impact the lives of people with cancer.

Which brings me to the main topic of today’s discussion

There are many challenges in cancer drug development, not least of which are regulatory hurdles, time consuming, risky and expensive clinical trials (we’ve seen a lot of phase III failures lately), basic research, biomarker development and many others. Traditionally, cancer trials take two main strategies to market:

  • Head to head comparison with standard care or a with and without approach if adding a new agent to the combination
  • As a single agent in the relapsed, refractory setting

Both of these approaches are typically tested in the advanced or metastatic setting when the disease burden is relatively high and the risk of a drug failing in phase III trials is also high. In solid tumour cancers, once a drug has been shown to be effective, studies tend to move into the earlier, adjuvant setting after surgery has taken place but these trials can take a very long time to reach fruition, typically 5-10 years in some cases.

For many of us, the challenges of how to think outside the box and speed up development while treating earlier stage of disease more effectively has occupied many thoughts. Sometimes the bureaucracy across so many functions is just mind boggling.

No more.

Dr Desmond-Hellmann was telling me about the Investigation of Serial Studies to Predict your Therapeutic Response with Imaging and Molecular Analysis (I-SPY) project, which was launched in DC this morning and aims to change the way we think about cancer drug development.

“What’s really neat about the I-SPY trial is that Laura Esserman, the PI of the trial, is a breast cancer surgeon here at UCSF and has added so much value to the project because she sees patients early and has a unique opportunity to offer neoadjuvant therapy.

Patients are getting their primary therapy before they get surgery, so for imaging and biomarkers – either established or exploratory – it is a fantastic opportunity. The endpoint is pathological complete response, so you can see if the tumour has disappeared or not.”

Treatment with therapeutics prior to surgery is known as neoadjuvant therapy and has a much shorter time span (around a year) for collecting results than adjuvant trials.  Furthermore, Dr. Hellmann elaborated what is exciting about this new approach:

“It’s a fantastic rapid readout model so you can get answers much more quickly in a year, including pathological specimens, along with the answers from biomarkers and imaging, which are important.”

The FDA has allowed a master IND agreement for this study, so it will be possible to move agents in and out of the trial quickly. So if agent A looks promising it can be advanced quickly and more patients put on it, but if agent B looks toxic, it can be discarded quickly. It’s not just a clinical trial, but a experimental trial process that gives you a rapid readout of whether the agent works or not.

The hope is that you won’t be wasting time and money in phase III trials, but most importantly, patients experience on that molecule.  If the answer is yes on I-SPY, you then have a biomarker hypothesis for that agent and can then do a more traditional phase III trial having increased your chances of success.

In this way, we will also learn more about the biology of the cancer and effectiveness of the treatments earlier in the course of the disease, which may lead to better long term survival than if treatment is delayed to the later stage of disease, when the cancer has spread and metastasised.

You can find out more about the clinical trial process here and here.

The trial will look at the following protocol:

Picture 28
Source: I-SPY2.org

For breast cancer, the standard of care is paclitaxel followed by four cycles of anthracycline therapy.  In this model, women with breast cancer can also receive other therapies, either marketed or investigational, to see if their outcome can be improved. For this I-SPY2 project, the five initial investigational agents are provided by Pfizer, Abbott and Amgen:

  1. ABT-888 (veliparib) from Abbott, is a PARP inhibitor
  2. AMG 655 (conatumumab) from Amgen is an APO/TRAIL protein that causes apoptosis
  3. AMG 386 from Amgen is a VEGF angiogenesis inhibitor similar to Genentech’s Avastin
  4. CP-751,871 (figitumumab) from Pfizer is an IGF-1R inhibitor that targets the insulin receptor
  5. HKI-272 (neratinib) from Pfizer is a Pan ErbB inhibitor similar to Herceptin

None of the I-SPY-2 breast cancer project would have been possible without the passion, energy and enthusiasm of women such as Drs Sue Desmond-Hellmann, Laura Esserman or Janet Woodcock of the FDA, who has been pressing for more creative solutions to fast track better cancer drugs for some time.  This consortium is particularly fascinating to watch because it brings together the major players – academia, industry and the FDA, in a way that has never been done before.  We should salute their originality and endeavour to think, and more importantly, do things differently.

If the basic concept proves successful, such a revolutionary clinical trial process may well become the new model for early and more effective drug testing, not only in cancer, but also for other diseases such as alzheimers, diabetes and other chronic diseases. In the long run, this approach may also lead to lower healthcare costs by improving efficiencies.

While Dr Hellmann was excitedly describing the process, I was thinking how much intuitive sense it makes and wished that the bureaucratic hurdles to more collaborative academia-industry-FDA clinical trials had fallen long ago.

The important thing though, is that it’s actually happening right here, right now and for people with cancer, that is good news indeed.

The future of Oncology… is in neoadjuvant therapy and biomarker led trials.

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RNAi and cancer therapeutics

By on March 16, 2010

One of the new trends I've noticed recently has been the uptick in research on RNAi in basic oncology research.  While searching for some information, this news release popped up from this morning:

"Tekmira and Pfizer will collaborate on evaluating Tekmira's stable nucleic acid-lipid particle (SNALP) technology to deliver small interfering RNA (siRNA) molecules provided by Pfizer. Tekmira will be responsible for preparing the SNALP formulations and Pfizer will evaluate the formulations in preclinical models. Financial terms of the collaboration were not disclosed."

Interesting.  

Furthermore, the release went to explain more about RNAi technology:

"RNAi therapeutics have the potential to treat a broad number of human diseases by "silencing" disease causing genes. The discoverers of RNAi, a gene silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi therapeutics, such as "siRNAs," require delivery technology to be effective systemically. Lipid nanoparticles (LNPs) are one of the most widely used siRNA delivery approaches for systemic administration. 

Tekmira's SNALP (stable nucleic acid-lipid particles) technology is the leading class of LNPs being used in clinical development. SNALP technology encapsulates siRNAs with high efficiency in uniform lipid nanoparticles which are effective in delivering RNAi therapeutics to disease sites in numerous preclinical models."

April heralds the annual AACR meeting in DC and while browsing the program last night, it was clear that this is an emerging area.   More on RNAi technology developments will be updated after the meeting next month; it looks like a fascinating new platform that is well worth exploring.  

Of course, this is not news to my cancer researcher buddies, many of whom have been working in this area for some time, but it's always good to see things begin to reach the more mainstream consciousness too.  Novel nanotechnology ideas were discussed at the AACR Molecular Targets meeting last November so we'll see what the next meeting brings.

If anyone is going to AACR in DC, do let me know – it would be great to meet up in person.

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