Cell Therapeutics FDA Panel Primer: What You Need to Know to Be Ready Next Week

2/3/10Follow @xconomy

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about $150 million annually in U.S. sales. The FDA’s deadline to make a decision is April 23.

The FDA’s advisory panel meetings can dwell on the most arcane and tangential of scientific questions, but the ultimate question usually comes down to whether the panel thinks that the evidence presented for a drug is strong enough to show that the benefit outweighs the risk—or whether more proof from clinical trials is necessary. Adam Feuerstein, an influential biotech columnist of TheStreet.com, published his seven-point case on what he sees as the weak spots in the Cell Therapeutics application.

The 140-patient study on which Cell Therapeutics’ case heavily relies is known as Extend or PIX 301. This study randomly assigned patients to get pixantrone or the physician’s choice of another chemotherapy drug. The study’s main goal was to show the treatment could completely wipe out tumors. The study reached its goal, and the finding was statistically significant. About 20 percent of patients on pixantrone (14 out of 70) had a “complete response” compared with 5.7 percent (4 out of 70) who did that well in the control group.

What about side effects? Patients in the pixantrone group had higher rates of white blood depletion, known as neutropenia, with 41 percent reporting a severe case of that effect, compared with 19 percent in the control group, according to data presented in June at the American Society of Clinical Oncology. An even more severe form of that condition, febrile neutropenia, was found in 7.4 percent of pixantrone patients, compared with 3 percent in the comparison group. There were also more cases of severe cardiac disorders reported among patients who got pixantrone—8.8 percent on the drug, compared with 4.5 percent in the control group.

While cancer drugs are allowed to have greater side effects than a new pain reliever … Next Page »

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  • http://mchl.nelson2@gmail.com michael

    this drug doesnt sound to safe-if it causes heart to malfunction and people die from this,what exactly is the heart problem and can this problem be delt with so that the patient isnt adversly effected in heart?,or is it killing off heart tissues an so cant be remedied, can some protective or antidote in the heart be used while pix is doing its stuff on the cancer?Ben

  • Nick

    I’ve lost money in this stock before with the belief that pixatrone would get approval back in September. I truly believe that nothing has changed and they are hiding a lot of clinical data from the FDA. If the drug was determined to be effective back in September, could the company really modify a drug and have it ready in less than a year? I think not.

  • http://www.xconomy.com/author/ltimmerman/ Luke Timmerman

    Nick–I’m not sure why you would have expected Cell Therapeutics to win approval in September. They turned in their new drug application in June, and even if the FDA had granted an expedited six-month review, it would have been approved in December at the earliest. But the FDA granted its usual 10-month review, meaning that the deadline for making a decision is now April 23.

    There’s no way the company could modify the actual drug without starting over and doing a bunch of more clinical trials. We’ll hear what the FDA staff has to say in its lengthy report for the advisory panel, which should be out Monday morning, 48 hours before the committee meets.

  • http://marketwatch.com Chris

    I believe that Pix has remarkable results and that it will get approved. Go to the yahoo message board and you will find an oncologist who says he will recommend pix to his patients. The results show that pix is on average 4 times more responsive then an current chemo availible in the field. I would like to know if you had the choice what drug you would chose with the information laid out in front of you. There is no comparison pix would be my choice.

  • http://www.xconomy.com/author/ltimmerman/ Luke Timmerman

    Chris–does this oncologist you cite list his or her name and affiliation? And exactly what kind of oncologist do you think spends time trolling around on Yahoo Message Boards?

    Most oncologists haven’t studied the data in great detail, and aren’t in a position yet to comment intelligently about the pixantrone application. We’ll see what the panelists have to say next Wednesday.

  • Jason

    Chris,

    If there’s no statistical evidence that pix prolongs the patients life as this article suggests, than this combined with the higher toxicity rate i’m afraid will point to the panel giving the thumbs down for their vote. They’ll probably advise that more trials will need to be done.

  • http://marketwatch.com Chris

    Luke- I know two things you are not an oncologist and second you must have some resentments for losing some money with ctic in the past.

  • George

    Really Pix is Toxic? what about the release on Dec 8th that was published in a medical journal that states “Cell Therapeutics, Inc. (CTI) announced an abstract to be published online at the journal Blood website by M. Hacker, et al. demonstrating significant reduction in cardiac cell toxicity with pixantrone compared to currently marketed anthracyclines.”

  • George

    Also, if Pix was not a suitable drug then why has Europe allowed it on a named patient basis?

  • http://www.xconomy.com/author/ltimmerman/ Luke Timmerman

    Chris—you’re correct that I’m not an oncologist. But I have covered quite a few FDA advisory panels, and have been writing about cancer drugs for almost nine years. I have never invested a nickel in Cell Therapeutics or any other biotech company.

    Who is your oncologist source? If this person has an informed view, and would like to go on the record and answer my questions, I’d be happy to talk to him or her.

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  • Chris H.

    Luke,
    What are the chances that ODAC allows this drug approval under sub part H and that they are required to run additional trials to show survival and reduced toxicity levels compared to the currently marketed anthracyclines?

  • http://marketwatch.com Chris

    Luke- Here is the article.

    Posted by: Zoofire Date: Tuesday, June 02, 2009 7:35:06 AM
    In reply to: bkbirge who wrote msg# 2169 Post # of 3789

    Written by a medical doctor in reply to someone from theStreet.com that doesn’t know what he’s talking about:

    I would like to post this content from the hotest NNTP in the land (pre-approved by the author). Thank you much.. Authored by: abducens2006 (MD)

    I wanted to write a detailed explanation of why I felt Feuerstein is wrong yet again earlier today, but I didn’t have time. Unlike Feuerstein, I actually take care of patients with cancer, and I wanted to take the time to review CTIC’s poster carefully before commenting further on it. So, here is goes….

    Feuerstein is up in arms over the cardiotoxicity data presented on CTIC’s poster. First, Feuerstein criticizes CTIC for not reporting the MUGA scan results for 36 patients on the pixantrone arm of the study. Did he bother to read that >70% of patients had an IPI>2, and >70% had stage III or IV disease? An IPI score of at least 2 correponds to intermediate or high grade disease

    . Patients with stage III or higher represent a population of patients with advanced disease. Did he bother to read that these patients were on at least their third or, in some cases, fourth chemotherapy regimen? In other words, these patients had advanced disease, and were in a salvage setting. So, unfortunately for these patients, they are more likely to fail treatment and experience side effects. So, it is not surprising that 70% discontinued pixantrone (vs 75% for the comparator group), and ultimately 58% died before the study concluded. I would like Feuerstein to explain how a physician can ask that 36% of patients who are probably going on hospice to have a MUGA scan before they die. That’s ridiculous. I’m frankly amazed that they were able to get MUGA scans on 40% of pixantrone patients all the way through, given the 70% discontinuation rate and 58% death rate. Were there any deaths attributed to pixantrone? Not based on these data. No grade 5 events were noted. So, Feuerstein’s ridiculous statement about the 36% unreported MUGA scans just shows he has no clue how to interpret data properly, and worse yet, he has no concept of what a patient/family go through who have cancer.
    Next, he makes a big deal about 5% decline in LVEF, like pixantrone is some horrible drug. Newsflash, Adam, 5% LVEF reduction does NOT correlate with clinical significance. I guarantee you, if a patient with an LVEF of 55% drops to 50%, the patient will not be symptomatic. Plus, many times MUGA scans or echocardiograms may have subjective interpretation, and the 5% may not be accurate anyway. To me, Feuerstein obsessing over this 5% reduction in LVEF is just silly, and shows he has no experience in clinically managing patients with cancer. To add insult to injury, he makes some snide comment about the comparator arm getting a 1% gain in LVEF. So, Adam, does that mean we should give chemotherapies on the comparator arm as a treatment for CHF? Of course not. Could it be that 1% is subjective, and not worth obsessing over?

    Furthermore, he makes note of CTIC’s serious cardiac disorder of 8.8%, but refuses to acknowledge that rate is much lower than historically treated patients with anthracyclines, right there for him to see on the poster. Plus, the comparator arm had a serious cardiac disorder rate of 4.5%, so does that mean all chemotherapies are banned for usage in these patients as well? Of course not. I’ve got news for Feuerstein, chemotherapy is TOXIC, and therefore is associated with side effects. That is inevitable. If Feuerstein ever knew a patient that had cancer, or he himself ever got cancer, he would understand that. For oncologists, we understand that certain chemotherapies are going to have serious toxicities. The payoff depends on benefit. For example, did Feuerstein criticize avastin for Genentech with its 12% risk of stroke/pulmonary embolism/DVT as reported by Duke in glioblastoma patients? Or the 3% risk of intracranial hemorrhage? Guess what? Avastin was FDA approved recently for recurrent glioblastoma, knowing full well these risks are reported in clinical trials. In other words, just because a drug has a low risk of a serious adverse event does NOT disqualify the drug from FDA approval. Avastin very clearly shows this, and I would love to see Feuerstein try to worm his way out of that one.

    In addition, he took shots at CTIC for the lack of statistically significant data on overall survival. Someone please remind the resident biotech guru at thestreet.com that 55 people are still alive, and you can’t calculate overall survival reliably until enough time has passed. Furthermore, did Feuerstein even bother to read the chart for time to progression, which clearly shows a subgroup of patients out as long as 25 months? CTIC cannot comment on overall survival with any degree of accuracy until these patients who are still alive are followed out until their death. That sounds morbid, but it’s true. So, for him to rip CTIC for this one is just wrong.

    Did he notice progression free survival was improved on the pixantrone arm, and it was statistically significant? Know why? The response rates were clearly far superior on the pixantrone arm.

    Lastly, did Feuerstein even bother to note that 15% of the patients on the pixantrone arm previously had stem cell transplants? That means they received super high doses of chemotherapy that ablated their bone marrow, and received a transplant to regrow their bone marrow. So, again, we’re talking about a patient population that is at greater risk of toxicity. I’m frankly amazed the toxicity in this trial was not worse.

    I hope investors take some time and due their DD, rather than listen to an unqualified political science major masquerade as a biotech consultant.

    I personally think the response data are very encouraging. I think the data on cardiotoxicity, while not perfect, are acceptable, and show a reduction in historically evident cardiotoxicity in patients treated with anthracyclines. I believe all toxicities are manageable, and I would not hesitate to offer pixantrone to a patient based on these results. I think the demographics are well-matched, and the trial was conducted in a randomized, controlled fashion, and that is quite good. I believe pixantrone will achieve FDA approval, and I can’t wait to hear Feuerstein’s temper tantrum. Is he going to blame Renaissance Technologies for sabotaging his agenda against CTIC?

    I think Adam Feuerstein is not qualified to comment on biotech stocks. I think CTIC should file a lawsuit against him for slander, because his accusations are childish, immature, incorrect and based on malicious intent. I think thestreet.com should fire Feuerstein and consider hiring a physician who has experience in clinical trials to write these articles. Feuerstein is not qualified to comment on clinical trials, and should not be allowed to report on anything related to medicine.

    There, now I’m done.

    Almost: Yes, there is enough data to conclude pixantrone is acceptable, in terms of risk, to use on lymphoma patients with advanced disease with few options to help them. I am confident this data will be enough to get FDA approval. Once again, avastin has 12% risk of stroke, pulmonary embolism and blood clots based on data from Duke, and yet it was approved BY THE FDA for glioblastoma patients. I mean, geez, if your logic made sense, avastin wouldn’t be used across the world for patients with high grade brain tumors. Do you get that?

    -Abducens

  • A.D.

    “….Assuming Cell Therapeutics captures one-third of the patient population, pixantrone could generate about $150 million annually in U.S. sales…..”

    A few questions:

    What would you presume the other two thirds of patients who have failed to respond to previous treatments would get for therapy?

    Why did you in your calculations disregard sales outside the US?

    How did you come to the conclusion that guy at thestreet.com is influential and even knows what he is talking about?

    You seem somewhat biased to me.

    Thanks

    A.D.