GLG News by Kenneth Algazy, MD

Implications: "In summary, rFVIIa reduced hematoma growth but did not reduce the rate of death or severe disability after intracerebral hemorrhage."

Analysis: Further study may show a way to make this work, but for now forgetaboutit.

Implications: Glaxo is trying to move Tykerb ahead of Herceptin in a first line/neoajuvant/adjuvant setting in Her2Neu + Breast cancer.

Analysis: Logical but risky. If it loses it will be no worse off than where it is placed now, but if it wins the sky is the limit in Her2Neu + breast cancer. My guess?? No idea, but the oral Tykerb would be appreciated by patients but not oncologists who will make no profit from an oral agent.

Implications: Erbitux was touted to have a positive study in Non Small Cell Lung Cancer (NSCLCA) but all they said was that is was a positive study. No further info at that time but an executive bought a block of stock a few days before the announcement which led to an inevitable rise in the stock price! Does this mean the trial is not as positive as we were led to believe?

Analysis: There is positive and then there is positive!! Was there statistical significance??? We have no idea, but many were annoyed by the premature release of data without any meat. What does MS know that we don't?? This is scheduled for a plenary session at oncology's national meetings. If the data is less than spectacular there will be a great deal of disappointment.

Implications: Myriad Genetics Inc. went directly to the patients who then were tested whether the tests were indicated or paid for by insurers or out of their own pockets. If patients have "medical savings accts" as suggested by various political candidates, right or wrong patients will want it with this kind of advertising pressure.

Analysis: This is again the tip of an iceberg. Any one that even thinks they have a family history of a malignancy will want testing for them and their children. Insurers will most likely NOT pay for testing but there is enough cancer paranoia out there that genetic testing will grow whether indicated, reimbursed or not.

In the past I have pointed out that genomic's time has come. The science is there and the patients are motivated. What more does the investment community need to know?

Implications: GDC-0449 is an oral agent that will be added to "standard" therapy in metastatic colorectal carcinoma (CRC) and evaluating progression free survival as the primary objective.

Analysis: Good trial with an appropriate randomization. This should tell us if the agent has a future in this rather common cancer. A well spent 3 million dollars by Genentech. Chance of benefit?? At least the study is designed to answer the question.

Implications: An interesting randomized phase II trial of Gemzar (the current standard with Tarceva) vs imexon + Gemzar. BUT shouldn't it be compared to Gemzar/ Tarceva??

Analysis: Even if better than Gemzar, it needs to be better than Gemzar/Tarceva and this isn't being tested (??) You won't be able to compare one to the other without a direct trial so I am not sure how the FDA will look at the result.

Tarceva (Genentech) does add much but it is better than Gemzar alone so what will this trial prove?? I'm not sure.

Implications: Approval will be base on the phase III INTEREST trial that showed in NSCLC that Iressa was "non-inferior" to standard chemotherapy after platinum therapy failure first line. Iressa was better tolerated and had an improved quality of life.

Analysis: Iressa is on life support in the US but it appears potentially alive and well in the rest of the world. Tarceva (Genentech) has supplanted Iressa in the US probably related to poor trial design and dosing in the initial trials. This will give AZ life outside the US and may "leak" into the North American market it they can get around the original failure as well as Tarceva's success.

Implications: Gene mutation analysis can help refine therapy in acute leukemia and impact on results!!

Analysis: I have said in the past that eventually all neoplastic tissue will undergo gene analysis to pinpoint the most effective therapy. INVEST IN GENOMICS!!!

Implications: Rituxan failed to improve various parameters and targets in a rather comprehensive study of patients with Lupus.

Analysis: Let's not panic!! I have not seen the data but there may be some subsets that benefit, so wait for a complete analysis. In addition as a hematologist/oncologist we use Rituxan in any disorder that is of an immune nature whether neoplastic or benign. These include besides lymphomas, coagulation disorders and immune thrombocytopenia. The market may be reduced but there are still multiple uses that remain to be explored

Implications: ZymoGenetic appears to have a biologic that will expedite lymphocytes apoptosis (destruction) when combined with Fludara and Rituxan- 2 standard agents in this rather common & occasional refractory condition.

Analysis: Cephalon just received approval for Treanda in CLL and now  ZymoGenetic
has IL-21!! Rather impressive logarithmic jumps in our ability to treat this sometimes refractory disease. http://bloodjournal.hematologylibrary.org/cgi/content/full/111/9/4424-a
outlines other possible uses so this is not just a "one trick pony." Stay tuned

Implications: This non erythropoietin (Epo) product will raise hemoglobin levels and decrease the need for transfusions.

Analysis:  BUT, will this drug produce the same problem that Epo products do, namely strokes, coronary artery problems and tumor growth?? Approval will have a rather high bar to jump unless they convince the FDA that the different mechanism of action makes a difference.

Implications: Doubles survival BUT "comparator" arm is best supportive care. See http://investor.poniard.com/ReleaseDetail.cfm?ReleaseID=306218

Analysis: Great but according to http://investor.poniard.com/ReleaseDetail.cfm?ReleaseID=306218 the study was a phase II and until it is compared in a phase III study & preferrably not with a "historical" control we cannot make any conclusions.

Implications: Thalidomide literally started the improved outlook in MM along with, and followed by Velcade, Revlimid and Stem Cell transplants. To now have increased access in Europe should open up that market eventhough the other agents are in widespread use (I think)

Analysis: I took it for granted that Thalidomide was routinely available in Europe. The fact that it was not means to me that sales will increase dramatically in primary therapy as well as salvage and post transplant maintenance

Implications: A major insurer (Wellpoint) is using the guidelines of the FDA to restrict erythropoietin (Epo) use.

Analysis: Given time all of the insurers will fall in line. No Epo in curable and other advanced malignancies. Not a surpise and will further curtail use of Aranesp (Amgen) and Procrit (J & J.)

Implications: In MCRC FOLFOX which involves infusional 5FU has been the cornerstone of therapy. This study shows that an oral 5FU substitute, Xeloda, can replace the IV 5FU and expedide care and avoid cumbersome infusions.

Analysis: 5FU is cheap but inconvenient to administer in the FOLFOX regimen. Changing it to Xeloda in XELOX benefits the patient as well as ROCHE. This has always been one of my favorate agents due to potential for taking over for the generic 5FU in the metastatic setting and also in the lucrative adjuvant market (post operative when all the disease is "gone." Also in Rectal as well as Anal and upper GI neoplasia. It is only a matter of time until all of the data matures and Roche I am sure will be rewarded.

Implications: "ASA404 is a Tumor-Vascular Disrupting Agent (Tumor-VDA) that selectively causes the collapse of existing tumor blood supply leading to extensive tumor cell death." It is being combined with Taxol and carboplatin in a randomized phase III study.

Analysis: Good company, large (1200 patient) trial in 20 countries on the basis of a + randomized phase II trial. Novartis appears to be giving it an excellent opportunity to succeed if there is anything here. I would not at all be surprised if they have a winner!

Implications: Alimta will be used first line with Cis Platin as a primary therapy for non squamous non small cell lung cancer (NSCLCA)

Analysis: In my mind this is major, and it is only a matter of time until it is approved in the US for first line use. It is a non toxic, effective agent that can be repeated monthly for years. In the US it will be modified by the practitioners to be given with carboplatin. I see a bright future!
The only ones who will be adversely effected will be Taxol (generic) and Taxotere (Sanofi) who will have to share the first line market.

Implications: 2 Texas U.S. Reps think that physcian owned hospitals are OK?

Analysis: I grew up medically in a community with physician owned hospitals on every corner. They were typically 20 beds and their reason to exist was not altruism but Profit!!! Any small specialty hospital is designed to maximize physician income, NOT patient safety or care. Unless they are part of a large chain with significant oversight, they have a tendency to slip towards the "dark side."

Implications: Co payments which had been $5/10/20 in the past are now a %age of the cost. When the cost may be upwards of $50-100K and you have a 20% co pay you can see the costs that are transfered back to the insured.

Analysis: This really can't continue. Drug co's always ask us how much more they can charge for a product that is an advance over the prior agents. I don't think our society is going to stand for this, especially if there is an administration change in Washington. Asking patients to pay $10-20K out of pocket yearly is a little excessive.

Implications: Has Avastin "hit the wall" as far as increased sales are concerned? Growth in the breast cancer market has not been as exuberant as expected.

Analysis: Relax, additional studies are being done to expand use in the lung cancer market which is every bit as large as breast cancer's and will make up the difference. When the new data matures we may see an expansion of who can receive it in the lung cancer population. Lets see what the June's American Society of Clinical Oncology (ASCO) meeting says.