Crowley Decides Against Senate Run

Asbury Park Press is indicating the John Crowley, CEO of Amicus Therapeutics and an ex BMSer has decided not to run for the Senate seat. There were rumors earlier that John might be getting ready for a Senate race on a Republican ticket. But looks like the political career is a bit far off for John.

Drug industry layoffs

Since Pfizer's last quarterly investor teleconference, a steady trickle of news-releases from large pharma companies has hinted that the second half of 2008 will be a tough one for a lot of pharmaceutical industry employees. JnJ, BMS, AZ, SP, all have announced plans for workforce reduction.

Pfizer, the world's biggest drug company, is eliminating 10,000 jobs, 10 percent of its work force. Merck is shedding 7,000 jobs, AstraZeneca (NYSE:AZN) is slashing 7,600 positions, Schering-Plough has furloughed about 1,100 manufacturing workers and Bristol-Myers Squibb will cut an unspecified number of jobs by year's end.

While there is nothing good about layoffs in general, demand for new employees continues to be strong, especially in Oncology and other specialty areas. But that could change quickly if the economy goes south and stock market tanks.

Axtinib Phase II Study Shows Promise in Pancreatic Cancer

Pfizer's multi kinase VEGFR inhibitor axitinib has shown interesting results in Phase II study in Pancreatic cancer.

Interim results from a Phase II trial: axitinib + Gemzar median OS 6.9 months vs 5.6 months for single-agent Gemzar - a 26% reduction in the risk of death. In a subset of 94 patients with a good performance status, the combination reduced the risk of death by 33%

Word on the street is that axitinib is about to move into Phase III in pancreatic cancer - in 2H 2007

Gardisil has a competitor

In an article published in journal Lancet, Glaxo Smith-Kline announced that their HPV vaccine Cervarix has completed the pivotal clinical trials, and it is highly effective against HPV, and cervical cancer.

The researchers concluded that Cervarix appears highly effective in preventing HPV and ultimately cervical cancer among women aged 15 to 25 years. Only future trials will determine the clinical utility of the already approved cervical cancer prevention vaccine Gardasil® and Cervarix.

Glaxo plans to file marketing applications all around the world, which in some ways should give Merck some concern. Cervarix will compete with Gardasil for the same patients. On the other hand, it should bring some relief to Merck to have two companies promote the virtues of a vaccine than one, given the controversy surrounding the promotion of the vaccine as a means of promoting immoral behavior among young women.

NY Times has an interesting article on how the vaccine development was fraught with difficulties. Makes for an interesting reading.

RON receptor involved in Pancreatic Cancer

Recepteur d’Origine Nantais, or RON receptor tyrosine kinase and its ligand, macrophage-stimulating protein, have been long implicated in progression and metastasis of tumors including breast cancer. Now comes a study from the scientists Andrew Lowy, MD, and Susan Waltz, PhD, at University of Cincinnati that implicates involvement of RON in aggressive pancreatic tumors.

From their press release

The team found that the RON receptor was active in 93 percent of what is known as pancreatic intraepithelial neoplasia, an early form of pancreatic duct cancer. In addition, the receptor was present in 79 percent of primary pancreatic cancers and 83 percent of metastatic cancers

You can get the July 1 issue of Cancer Research to read the entire article. Articles are posted free online after three to four weeks of publication. Look for Ryan Thomas, et al publication titled, "The RON Receptor Tyrosine Kinase Mediates Oncogenic Phenotypes in Pancreatic Cancer Cells and is Increasingly Expressed during Pancreatic Cancer Progression"

Sunitinib to be tested in first line mCRC

Pfizer is moving into metastatic Colorectal cancer with the announcement of a multinational Phase III study with sunitinib malate, Sutent. The study will enrol 700 patients in South America, Canada, Europe and Asia. Conducting a first line study would be a herculean task in the United States as the first line is pretty much the domain of Avastin based therapy.

Penetration in first-line use is probably at or above 75%, according to (Jason) Napodano (of Zacks Equity Research). Over the next few quarters Napodano predicts that Avastin can achieve near 80% penetration in this indication.

For more details click here

Hence increasingly companies in Oncology arena are embarking on conducting multinational trials where they can ask the questions worth asking about the activity of the compound. Question is, how do you get a drug registered in United States based on a study done out side of United States? And the answer may be while that it may be difficult to get the first indication for a new drug based on a study done entirely outside of US, perhaps its not unthinkable to approach the FDA for a new indication for a drug that is already on the market, with ex-US data. Still, it would not be impossible to source a few patients in the US, despite the Avastin's looming presence.

All this is nothing but good news for the patients as more options mean more chances that one will find something that works!

Temsirolimus bring new hope to renal cancer patients

Temsirolimus is a new drug from Wyeth which brings new hope for patients with the most agressive form of Renal cell cancer. Temsirolimus was originally slated for approval in march/april 2007, but FDA requested additional information to ascertain whether the drug indeed had an impact on tumor growth. From yesterday's action it appears that FDA is satisfied that the drug will help patients.

What is temsirolimus? Temsirolimus is a mTOR inhibitor, where mTOR stands for mammalian target of rapamycin. In normal cells, the pathway called PI3-AKT pathway plays an important role in regulation of cell growth. In studies scientists have found that in cancerous cells, PI3 and AKT proteins (kinase enzymes) are present in large amounts, resulting in constant signaling to cell to continue to multiply (a cancerous cell is essentially a cell that does not know when to stop multiplying). What has also been found that if you block or inhibit mTOR enzyme, this prevents the signaling to the nucleus to continue to multiply. A drug that seems to have this property is Rapamycin, an old macrolid antibiotic. Since this discovery, scientists have been trying to develop Rapamycin like drugs that would have better activity, and could be given easily to patients. Temsirolimus is one of the first such drugs to get to the market. So, Temsirolimus inhibits the mTOR enzyme in P13-AKT pathway to prevent the multiplication of cancer cells.

An activated PI3-AKT pathway is found in a lot of tumors, such as renal cell cancer, mantle cell cancer etc. Thus there is hope that mTOR inhibitors will be useful broadly. More importantly, it is thought that if mTOR inhibitors are combined with other traditional cytotoxics, and newer targeted therapies, they might be even more effective.

Naturally, like most drugs, Temsirolimus in not devoid of side effects. For instance, temsirolimus is known to have an impact on liver, can cause diabetes like symptoms (high blood sugar) which needs to be managed with insulin, and the FDA has asked Wyeth to provide more data on Temsirolimus' action on the heart (QTc prolongation).

Some people might also be hypersensitive to Temsirolimus, so this drug may not be for every renal cancer patient. But the good news is, just in last couple of years, Renal Cancer patients have seen significant improvement in treatments available to them. Sutent, Nexxavar, and now Temsirolimus are all important additions to the arsenal of drugs an oncologist needs for treatment of this dreadful disease which affects 50,000 patients annually in the US alone.

Temsirolimus provides modest benefit - in clinical trials, compared to interferon (which is a tough drug to take) it was shown to increase survival from 7.3 months to 10.9 months in patients with a very aggressive disease. But these additional 3 months are very valuable months for Renal cancer patients, so I hope that the drug proves to be useful to a lot of patients.

Chinese Cancer Market Opportunity

China is often touted as a great market for consumer goods. However there exists a great market in China for pharmaceutical and bio-technology products as well. A study recently released by the Ministry of Health provides an indication of the scope of opportunity.

As an example, compared to the 5 year survival rate of 60-70% in western Europe and United states, in China, the 5 year survival rate is about 25%. China has a fairly high number of cancer patients (about 3 million) and thanks to the high rate of pollution, smoking and poor awareness, is adding close to 2 million new cancer patients per year and about 1.5 million patients die of cancer.

The major types of cancers seen in China are (but not limited to) lung cancer, liver cancer, gastric cancer, oesophageal cancer and rectal cancer.

Hurdles remain including ability of the market to pay for some of the expensive drugs. But in terms of opportunities to develop drugs in China, the opportunity is wide open.