FDA panel recommends Avastin approval for Glioblastoma

By MaverickNY on April 1, 2009

The FDA Oncologic Drugs Advisory Committee (ODAC) met yesterday and unanimously recommended that Avastin offered benefit to patients with previously untreated Glioblastoma multiforme (GBM), a fatal form of brain cancer. If accelerated approval is granted on May 5th, it will be the first new treatment for the disease in 10 years.

The American Cancer Society estimates that 21,810 malignant
tumors of the brain or spinal cord are diagnosed per year in the United States; approximately 10,000 of these are likely to be Glioblastoma. GBM has a tendency to recur and relapse is common. There are few non-surgical options available to patients, so it represents an area of high unmet medical need.

What was so compelling about the Avastin data?

According to Genentech, the non-comparative Phase II data from the BRAIN study involved 167 patients, of who 85 received treatment with Avastin in combination with irinotecan and were compared to Avastin alone in patients who had previously progressed on prior temozolomide and radiotherapy. Primary endpoints included objective response rate and progression free survival (PFS). Secondary endpoints included OS and safety.

"In the 85 patients treated with Avastin alone, the trial showed:

In 28 percent, tumors shrank to at least half their original size;
In those whose tumors shrank, half experienced a response of at least 5.6 months;
43 percent lived six months without their disease getting worse; and
Half lived at least 9.3 months after starting treatment with Avastin and 38 percent survived longer than one year."

There were no new adverse events beyond those reported in previous indications for colorectal, lung and breast cancer.

There are few available treatments for patients who have relapsed after treatment with temozolomide (Temodar). Temozolomide is approved for the first line treatment of GBM and showed significant survival of 2.5 months when used in combination with radiotherapy (RT) compared to RT alone. It makes approx. $1B in revenues annually. I'll be curious to see how the phase III frontline trial shapes out, what the comparator arm will be and how well patients do on upfront Avastin. If the phase II refractory data is anything to go by, the results may look fairly promising.

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Jade Goody and cervical cancer

By MaverickNY on March 23, 2009

Yesterday, Jade Goody the UK reality tv star sadly passed away from cervical cancer. She was 27 years old.

Source: Daily Telegraph

Whatever else one may think about the furore and PR that accompanied her last few months, we cannot deny that she was very brave and probably did more for raising awareness of the condition than any other individual.

Cervical cancer is linked to the Human Papillomavirus (HPV) and vaccines such as Gardasil (Merck) and Cervarix (GSK) are now available to prevent the disease occurring in young women. Currently, there are 11,000 new cases a year in the US with 3,800 deaths. In the UK, over 700 women a year die from cervical cancer. The condition can be picked up early by PAP smears.

What was fascinating about the Jade story was that she got the conservative and shy Brits talking about death and dying in an open way that has rarely been seen in the country before. Even my mother discussed it despite not being able to talk about my father's death from prostate cancer a few years ago. Some cancers are slow growing, some recur, Jade Goody's battle was a short and very brutal one.

Cancer is devastating. It's not just a life-threatening illness. It can make
you poor, it can collapse your family life and it can have huge
emotional consequences. But most of all, it can leave you isolated and alone.

In the end, perhaps we should think more holistically about about the patient as a whole and not just treat the tumour. If more young (sexually active) women consider getting annual PAP smears and parents vaccinate their under 21 yo's, we may well see a decline in the death rate for cervical cancer in the future. If that happens, it may not bring the Jade Goody's of this world back, but at least the publicity and raised awareness will have achieved something lasting and impactful.

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Layoffs and Executive compensation at Wyeth

By MaverickNY on February 10, 2009

Well, it comes as no surprise that on top of the 18-20K layoffs announced from Wy-Pfi, the senior management team will be very nicely looked after, including the former Chairman and President. The five will be pocketing a princely $75M between them at a time when many will be worrying about their job security in a depressed market.

Details here.

Lessons learned from targeted therapy in cancer

By MaverickNY on February 10, 2009

The post earlier today about Genentech/Roche's continued success with Avastin and Tarceva got me thinking a little more about targeted therapies in general. Why do some succeed where others fail? Why did Tarceva do well, whereas Iressa did not? Why did Avastin prove efficacious while vatalanib and others did not?

Why indeed.

If you look at some of the successes – Herceptin, Gleevec, Tarceva and Avastin, for example, several patterns emerge:

1) Make sure you have a target to aim for.
2) Is the target valid and critical?
3) If you don't know what your target is, you won't be able to hit it!

Flickr Photo Courtesy: Matthew McVickar

As often is the case, the simplicity of the message would also apply to life in general and not just to cancer biology and drug development. It's amazing how many people miss the obvious right under their very nose though, but get the target right, the delivery for hitting it right and success will ultimately follow.

Maintenance therapy in first line lung cancer

By MaverickNY on February 10, 2009

For years, the traditional treatment for newly diagnosed advanced non-small cell lung cancer (NSCLC) has been chemotherapy doublets – carboplatin-paclitaxel, cisplatin-docetaxel, carboplatin-gemcitabine etc so by the time patients progress to second line therapy they will be fairly beaten up and overall survival for the disease is sadly only a year or so for many patients. Chemotherapy has the disadvantage

Recent years have seen the advent of targeted therapies in NSCLC including Iressa, Tarceva and Avastin. Tarceva (erlotinib), an EGFR inhibitor, and Avastin (bevacizumab), a VEGFR inhibitor, are both produced by Genentech and Roche so it was inevitable that they would be combined at some point to see if the combination would be effective as maintenance therapy. It makes strong scientific sense to determine if it makes good sense to try to combat the cancer by treating both the
cancer cell’s growth and division signaling pathways (Tarceva) and
the supporting microenvironment by reducing the tumor blood supply (Avastin) as shown graphically below:

Click to enlarge

Yesterday, I spotted this item in my feed reader with the sensationalist headline of screaming, "Avastin-Tarceva combination fails in lung cancer"! Instead of purchasing the item, I checked out the company websites for more information. Lo and behold there was better information there on the two front-line trials that were investigating the combination.

The ATLAS trial was designed to see if Avastin with or without Tarceva as maintenance therapy was effective in squamous NSCLC patients after 4 cycles of standard chemotherapy with Avastin (every 3 weeks). According to Genentech and Roche:

"If their cancer did not progress and they did not experience
significant toxicity, patients were then randomized (n=768) to receive
maintenance therapy with Avastin plus Tarceva or Avastin plus placebo
until disease progression."

The study met it's primary endpoint, progression free survival (PFS). This means that Avastin and Tarceva in combination significantly improved the time patients with advanced lung cancer can live without their disease worsening.

A previous trial (SATURN), looked at the benefit of adding Tarceva as maintenance therapy after standard chemotherapy in NSCLC patients. The study reported that Tarceva significantly delayed disease progression compared to placebo.

These results offer new hope for lung cancer patients.

If patients have a squamous histology, they can be treated with 4 cycles of standard chemotherapy with Avastin, then Tarceva plus Avastin or Tarceva alone as maintenance therapy, while non-squamous patients can receive Tarceva therapy since Avastin is not suitable for those with a non-squamous histology due to increased risks of GI bleeding.

As for that Nature snippet on failure in second-line? Well, it makes more sense to treat with targeted therapies up front before the tumour burden is too great and the drugs will have a better chance of working. Competitively, this may also mean that the bar is raised for new entrants in first line NSCLC and Alimta and Taxotere will see more second line use going forward. The improved time to progression will also mean a delay in second line treatment.

All in all, these results are positive and we can expect that:

a) The results
to be presented at the forthcoming ASCO meeting in June
b)
Genentech and Roche to be discussing adding label extensions with the
FDA and EMEA.

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What is competitive intelligence?

By MaverickNY on February 3, 2009

“There are no secrets, only information you don’t yet have.”

Drop.io blog

Sometimes random thoughts on the internet can stimulate us in most unexpected ways, as this quote did with me today. In many ways, the statement is very true, at least as far as pharma competitive intelligence (CI) is concerned. Much of the information about products and companies is already out there, hidden in the huge mass that is the world wide web. Often, it is just a matter of superior search skills to ferret out crucial information or key people who may have access to the data you need.

Four things then become critical:

1. An in depth knowledge of the subject area in order to process what is important and what is not.
2. A logical and creative mind to find the information in the first place.
3. A relevant and useful network of contacts.
4. An ability to process both linear and non-linear data into valid patterns and trends as a commentary.

Is it an art or a science?

In the final analysis, like marketing, CI is a bit of both and one should never misunderestimate the power of intuition and gut feel. They sometimes make more sense than logic.

To me, it doesn’t matter if you use cool modern web tools or traditional methods as long as the data gathered is relevant and appropriate. Sometimes a mix of the two works well in tandem, sometimes one or the other is more useful.

However, there is nothing worse than getting a huge ‘book’ or summary sheets of data upon data and no analysis or interpretation. That’s NOT what CI is or should be, it’s undisciplined and inexperienced data gathering, much like imitation and processed cheese is very different from a crafted artisanal cheese. The old chestnut of quality over quantity still applies to CI to this day.

What does competitive intelligence mean to you?

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9rules… wow, a nice surprise!

By MaverickNY on January 20, 2009

After the recent euphoria of making it onto Alltop, this week I found out that the blog has made the latest round of 9rules, an independent website for cool and well written web content.

I applied last November for the first time and having checked out the
Round 7 winners afterwards, I really wasn't expecting to get in and considered it
a very long shot indeed especially for a site that is essentially a specialist niche within a niche. Imagine my surprise when I find out this blog made it
onto the list, especially while recovering from flu and a nasty cold! Hopefully, it will end up in the science section soon. But, hey I'm certainly looking forward to finding and reading some new blogs for my Google Reader myself. It's great fun learning from smart people, it's the fastest way I learn new things.

Check out the 9rules link above for yourself and see if any of the blogs listed take your fancy, there certainly were some superb ones in the list. Mine must have been the ringer ;-), but seriously, it's a great site with some excellent content in all sorts of categories.

Diesel fumes and lung cancer – hazardous to health or not?

By MaverickNY on January 14, 2009

I found this fascinating quote today:

"Recent research suggests that lung cancer risks are higher among trucking industry workers because of diesel fume exposure. According to a new study published in the January issue of the journal Environmental Health Perspectives, workers in the trucking industry with an estimated 20 years on the job have an elevated risk of lung cancer with each increasing year of work due to their diesel fume exposure."

Lung Cancer, whats that got to do with Delivery Drivers
This is a logical approach in the same way that number of pack years is relevant to the risks of developing lung cancer from smoking. What does other research say? Is there anything to back this assertion up?

Image via Wikipedia

"In 2002 the U.S. Environmental Protection Agency (EPA) released a Health assessment Document for Diesel Engine Exhaust. The objective of this assessment was to examine the possible health hazards associated with exposure to diesel engine exhaust (DE). The assessment concludes that long-term inhalation exposure is likely to pose a lung cancer hazard to humans as inferred from epidemiologic and certain animal studies."

Source: Inhalation Toxicology, 19(Suppl. 1):229–239, 2007

However, the US EPA research was somewhat flawed in that:

"Estimation of cancer potency from available epidemiology studies was not attempted because of the absence of a conﬁdent cancer dose-response and animal studies were not judged appropriate for cancer potency estimation."

Instead, chronic human health hazard is inferred from rodent studies which show dose-dependent inﬂammation and histopathology in the rat lung, so relative particle overload needs to be accounted for.

The EPA assessment conclusions are based on studies that used exposures from engines built prior to the mid 1990s. More recent engines without high-efﬁciency particle traps would be expected to have exhaust emissions with similar characteristics. The results of more recent trials from 2007-8 will help address some of the questions.

Interestingly, there are some reviews that concluded that there was insufficient evidence to support a cancer link, however the papers are potentially biased in that the lead authors were from the International Truck and Engine Corporation, so there was little incentive for them to declare such a link, anymore than a tobacco company would concede that smoking cigarettes is hazardous to health.

Scientifically and epidemiologically, one of the many things affecting the analyses is the significant changes over the last 20 years in engine emissions such as nitrogen oxide and other by products that may be hazardous to health. These have occurred with improvements and changes in the composition of the fuel and exhaust filters. There are currently new studies underway to evaluate the impact of newer fuels now that TDE has been removed from the fuel mix. One might postulate that as fuels have become cleaner, the risks associated with cancer may have lessened but time will tell.

Hopefully, cleaner fuels will offer fewer health hazards from emission by-products and lower the risk of cancer. The advent of hybrid cars is also a step in the right direction; who knows this may well help the US auto industry in the long run too.

Cancer and oncology links up to 1-9-2009

By MaverickNY on January 8, 2009

The value of new drugs is dropping – Jan 8th
"In 2008, the Food and Drug Administration approved 24 brand new
medicines, the most in three years. But medicines approved through June
produced lower sales than had been seen in the preceding decade." And yet in oncology, the prices (and presumably revenues) have been rising over the last 5 years. Interesting, perhaps it reflects the number of novel compounds rather than the me-toos seen in the consumer markets.

Skin cancer ups the risk of further cancers – Jan 8th
"Researchers studying nearly 23,000 cases of people treated for skin
cancer found that melanoma, the most severe form, was linked to double
the risk of having another primary cancer."

Poniard Pharmaceuticals to Present Data from Phase 2 Clinical Trials of Picoplatin in Colorectal and Prostate Cancers – Jan 7th
Lots of data coming out on picoplatin at ASCO and ASCO GI/GU meetings.

Human genomics in China – Jan 7th
An overview of progress in China – well worth a read.

Pfizer looks for a better way to detect drug risks – Jan 3rd
Although a general commentary, it is particularly relevant to oncology

Over hyped cancer drugs or sensational journalism?

By MaverickNY on January 2, 2009

Today I was thinking about what cancer drugs might be good to watch out for this year, such as abiraterone from Cougar Biotech currently being tested in prostate and breast cancers and Affinitor from Novartis, which is expecting FDA approval this year in renal cancer. A quick Google search turned up this article from the London Times and made me cringe at the following headline:

"Cancer drug could save the lives of 10,000 a year".

Oh dear.

The article talks about the potential impact of abiraterone in prostate cancer. Now, don't get me wrong I like both of these drugs and believe they will make an impact – on survival, but not as a 'cure' which is implicit in the saving lives byline.

Journalists often fail to understand the basics of cancer research. While the goal is to find a drug that induces remission or cure, in the meantime until our understanding of the science and biology improves greatly, we are stuck with expressing clinical trial results as 'survival', that is how long a patient lives compared to standard therapy. Otherwise, the only real known cures are surgery and stem cell transplant and even then not all are cured by either procedure.

There is a huge difference implicit in 'saving lives' versus 'living longer'.

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Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

Posts tagged ‘cancer oncology’

FDA panel recommends Avastin approval for Glioblastoma

Jade Goody and cervical cancer

Layoffs and Executive compensation at Wyeth

Lessons learned from targeted therapy in cancer

Maintenance therapy in first line lung cancer

What is competitive intelligence?

“There are no secrets, only information you don’t yet have.”

9rules… wow, a nice surprise!

Diesel fumes and lung cancer – hazardous to health or not?

Cancer and oncology links up to 1-9-2009

Over hyped cancer drugs or sensational journalism?