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  • Lemtrada Petitions 18 comments
    Jan 22, 2014 9:26 AM | about stocks: GCVRZ, SNY

    If you are interested in signing a petition in favor of approving Lemtrada as a new MS therapy, there are several ongoing petitions. For your convenience, here are links to each.

    Thousands of Multiple Sclerosis patients are getting worse each day; They need another Option, another choice

    Posted by Stu's Views and MS News

    There are currently 788 petitioners in support of Lemtrada. S. Mitchell Freedman, MD, FAAN, signed the petition and added that,

    I am a neurologist who has practiced for 35 years. Lemtrada is not for every patient but there is a substantial number of patients for whom it would be an appropriate treatment.

    Lemtrada for FDA Approval for Treatment of Multiple Sclerosis

    Posted by Lisa Dasis

    There are currently 327 petitioners in support of Lemtrada. One petitioner, Dr. Sheldon Robbins, said,

    Despite the fact that the FDA staff reviewers presented a series of questions that were structured to elicit a negative vote on adequacy of trial design and the efficacy of Lemtrada over Rebif, the panel members of the Advisory Committee voted overwhelmingly that the sponsor, Genzyme, provided adequate evidence of effectiveness. The panel voted unanimously that, assuming efficacy results are as they appear, safety concerns should not preclude approval.

    The FDA should convene a new advisory panel composed of MS experts who have the perspective and judgment to render the appropriate advice for approval of this transformative medication. US patients deserve the right to choose the appropriate MS therapy in conjunction with their physicians.

    I recently published a guest blog post on Lisa's site.

    Melissa Burdick - Citizen Petition

    Posted by Melissa Burdick

    You can comment directly to the FDA via this citizen petition. There are currently 16 comments in support of Lemtrada.

    Disclosure: I am long GCVRZ.

    Additional disclosure: Chris DeMuth Jr is a portfolio manager at Rangeley Capital, a partnership that invests with a margin of safety by buying securities at deep discounts to their intrinsic value and unlocking that value through corporate events. In order to maximize total returns for our partners, we reserve the right to make investment decisions regarding any security without further notification except where such notification is required by law.

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Comments (18)
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  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » The life story of a biotechnology drug: Alemtuzumab -- http://bit.ly/1g04jpW
    22 Jan, 10:29 AM Reply Like
  • Ruerd Heeg
    , contributor
    Comments (410) | Send Message
     
    From your post on Lisa's blog:

     

    "Neither patients nor bureaucrats want errors in deciding which drugs to approve. However, there are both “type one errors” (false positives in which a drug is approved that should not have been) and “type two errors” (false negatives in which a drug that should have been approved is rejected). For patients, they are both problematic. For regulators, all of their downside lies in type one errors. The FDA does not share the downside associated with waiting for a drug that could be saving or improving lives."

     

    "My hope and expectation had been that this would be a normal process involving evidence-based science. There was no reason for any controversy. However, the FDA turned this into a battle of the FDA versus MS patients, MS doctors, and clinical research. The FDA regulators have made clear that they can live with any amount of delay in the approval of new therapies."

     

    Spot on!
    22 Jan, 10:54 AM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » Thanks. -C
    22 Jan, 11:15 AM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » Striking a Nerve: Docs, Patients Fume Over Lemtrada Snub -- http://bit.ly/KIxtLj
    22 Jan, 06:44 PM Reply Like
  • TimeOnTarget
    , contributor
    Comments (2172) | Send Message
     
    Wow. I would have expected more comments on the citizen petition.

     

    It is really pretty easy. In fact, it is really easy. Click on the link, fill out a couple of boxes, name, contact info, and whether you are submitting for yourself or someone else.

     

    Then you just have to type in a box -- just like the comment boxes on SA.

     

    Regardless of whether you are an investor or not, you might want to consider commenting. My analysis of the situation is that it is just a downright lousy decision by the FDA that deserves to be overturned.

     

    Whether for themselves or someone they care about, at some point pretty much everyone will want the ability to obtain the most effective medication for a given condition or disease.

     

    It is in everyone's interest to ensure that the FDA approves those types of medications. It is important to understand that the FDA does have certain inherent biases because it is a governmental administrative agency and because of the particular role it plays.

     

    Chris, your comments that Ruerd quoted above get to the core of the problem. You noted essentially that they FDA is far more concerned with not making a mistake in approving a drug that shouldn't be approved than it is with not approving one that should. It is understandable why this bias exists: Consider, for example, the use of Thalidomide for morning sickness. Mistakes in approving a drug that should not have been approved will potentially unleash torrents of criticism and problems for the FDA.

     

    You noted that "the FDA does not share the downside associated with waiting for a drug that could be saving or improving lives." Exactly: Because the FDA employees don't typically share this downside, they are biased toward being overly conservative in deciding which drugs to approve. About the only thing that can be done to counteract that bias is a strong public and medical community backlash over the FDA's failure to approve a medication / treatment that it should have.
    23 Jan, 12:50 PM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » To save lives, reform the FDA: http://fxn.ws/1mJJ4X3
    26 Jan, 06:24 AM Reply Like
  • Ruerd Heeg
    , contributor
    Comments (410) | Send Message
     
    Thanks for the link. What I understand from it this article confirms your thesis that the FDA approval process shows some important shortcomings. Not only the FDA refuses to approve Lemtrada but it hasn't approved numerous other efficacious drugs and vaccines either, for which there are no alternatives, and that have been approved in Europe, Australia and Canada (long) before.
    26 Jan, 06:59 AM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » Is FDA's Approach to Adaptive Clinical Trials Stunting Growth of Molecular Medicines? http://bit.ly/1dZHIbh
    26 Jan, 06:25 AM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » THE DIGITAL FUTURE OF MOLECULAR MEDICINE: Rethinking FDA Regulation -- http://bit.ly/1dFXbam
    26 Jan, 06:25 AM Reply Like
  • TimeOnTarget
    , contributor
    Comments (2172) | Send Message
     
    This article is most definitely worth a read.
    27 Jan, 01:04 PM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » How The FDA is Killing Molecular Medicine: Q/A w Peter Huber -- http://bit.ly/1dFXfHc
    26 Jan, 06:26 AM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » Multiple sclerosis community voices disappointment with FDA ruling on new drug: http://post.cr/1aZ5le5
    26 Jan, 08:06 PM Reply Like
  • Ruerd Heeg
    , contributor
    Comments (410) | Send Message
     
    Thanks for the link. The article contains an interesting overview of the history of alemtuzumab. At the bottom of this overview it says the following:

     

    February 2016: The final data collection date for the third phase of Genzyme’s clinical trial.
    Sources: http://bit.ly/1d5GEwu, http://bit.ly/1ktQrpR, “From laboratory to clinic: The story of Campath-1”

     

    The deadline for the first commercial sales in the US is 31 December 2015 if the US is a Qualifying Major Market. If not then only US sales before April 1 2016 count towards the first sales milestone. So timing of the results of the phase 3 follow up don't not give us any chance of US sales counting towards the first sales milestone. An FDA approval in 2016 might help for the second sales milestone though.

     

    Note that the article mentions a treatment in the third year (on page 2), which would increase the chances of hitting the second sales milestone as well. Any info on whether a third treatment with alemtuzumab will become a standard procedure or not is more than welcome.

     

    I am also concerned about the off-label treatment, also mentioned in the article. Of course this is good for the patients but it is unfair play towards the rights holders. I wonder if the FDA can prevent this. I doubt the FDA will try to prevent off-label treatment anyway.
    28 Jan, 05:29 AM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » The FDA and More Treatment Options for MS Patients: http://on.wsj.com/1hFDOmo
    27 Jan, 03:34 PM Reply Like
  • David Thoms
    , contributor
    Comments (2) | Send Message
     
    Chris DeMuth Jr. I want to first say thank you for your posts and keeping people well I informed on the status of Lemtrada. I have signed the petition and wrote a letter directly to the FDA seeking approval for this drug. I have also asked friends and family to help In the efforts of its approval. My only concern is how long will it take before the FDA responds back to its appeal? I thought I saw somewhere that the FDA has until March or I may be confusing that with the GCVRZ deadline. Through all the articles I haven't seen some date or time frame for a decision. Or is this something that out of the blue the FDA will make a decision?
    27 Jan, 08:38 PM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » They will decide shortly. The process typically takes about a month.
    27 Jan, 08:51 PM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (4040) | Send Message
     
    Author’s reply » Letter to Dr. Woodcock from a concerned MD:

     

    January 29, 2014

     

    Janet Woodcock, M.D.
    Director, Center for Drug Evaluation and Research
    Food and Drug Administration
    10903 New Hampshire Ave.
    Silver Spring, MD 20993

     

    Dear Dr. Woodcock,

     

    The recent FDA decision to reject Lemtrada for use in Multiple Sclerosis was nauseating and a slap in the face to all US MS patients as well as the brilliant physicians who led the clinical trials.
    It also represents a misguided attempt to usurp the knowledge and judgment of physicians who treat MS. And it calls into question the very nature of the approval process with its lack of transparency and lack of accountability.

     

    To put this decision into perspective, there is no cure for MS and the underlying cause is unknown. It results in a shortened life span compared to the general population. The disease affects patients with different degrees of severity due to differences in genetic predisposition, differences in the innate immune system, and differences in the acute inflammatory response that define the disease. As such, no two MS patients are alike. Some MS patients experience relatively mild disease and current therapy works relatively well in delaying the incurable second phase of the disease, known as progressive MS. Some patients do very poorly and are forced to consider a more powerful medication known as Tysabri, which can cause a fatal neurodegenerative disease known by the acronym, PML. The risk of developing PML increases with the duration of therapy such that most MS physicians recommend discontinuation of the therapy after two years unless there is no choice due to intolerance or failure on the other therapies. These patients have to choose between the risk of developing potentially fatal PML or going off therapy and being ravaged by active MS. So, one can conclude that there is a definite need for an alternative therapy.

     

    To put this decision into further perspective, one should understand the nature of available therapies here in the US and what Lemtrada represents. The available therapies are called maintenance therapies and are given on a regular schedule. Patients inject themselves weekly or daily, they undergo monthly IV infusions, or they take daily oral medications, depending on disease activity and which medications they can tolerate. They do this for the rest of their shortened life span. The pharmaceutical companies are entitled to a perpetual annuity until the patents (or patients) expire and/or until they find another medication that "manages" the disease but, does not cure the disease.

     

    Lemtrada represents a new class of therapy known as an induction therapy. It is the first and only induction therapy approved in the rest of the developed world for MS. It is given as an IV infusion over five separate days and then again for three separate days a year later. The patient no longer has to take any therapy because a durable remission has been "induced" in the majority of patients. There can be side effects that develop during the infusion or that develop several years later but, the delayed side effects can be detected by periodic blood draws and managed appropriately. The remission can be so durable that some physicians think this medication could represent a cure for some patients.

     

    This historic and transformational medication was rejected by the FDA based on its own assessment that the clinical trials were possibly biased due to lack of blinding of the two treatment arms in the two phase III clinical trials. One of the lead investigators in the clinical trials, Dr. Coles, said, “Several years ago, we discussed the design of the alemtuzumab (Lemtrada) trials with the FDA at a face-to-face meeting. The FDA approved the trial design then."

     

    Advisory Panel chairman, Dr. Nathan Fountain of the University of Virginia School of Medicine said, "...most members of the committee appeared to be of the opinion that the drug demonstrated enough efficacy to be available for properly selected patients." On the significance of a potentially curative therapy, he said, "...a curative therapy for MS would be worth the seemingly high risk of a drug like alemtuzumab and would represent a foundational breakthrough in MS therapy."

     

    Several nationally recognized MS physicians and directors of MS treatment centers have voiced their frustrations and objections to the FDA decision.

     

    Dr. Stephen Krieger of Mount Sinai Medical Center said, "We have all seen patients do extremely well, who probably wouldn't have done so without alemtuzumab. There is a lot of disappointment among MS specialists."

     

    Dr. Edward Fox, from the Multiple Sclerosis Clinic of Central Texas, believes the FDA rejection is politically motivated and has more to do with the fact that Genzyme, the sponsor of the clinical trials, did not follow FDA directives. "There had been a large amount of communication between Genzyme and the FDA which I thought had been resolved. But it appears that the FDA wanted a double-dummy design, Genzyme didn't do it, and now the FDA is putting its foot down. They appear to be making a point. But I don't believe they ever said the drug would not be approved with that trial design. They allowed it to be filed and fast tracked. Individuals from the FDA made this decision, but they cannot dispute the overriding nature of the results. I want this drug available for patients with aggressive MS."

     

    Dr. Jeffrey Cohen of the Cleveland Clinic, another lead investigator of the clinical trials, said, "I have two disagreements with the FDA, "I don't think the double-dummy design would have been feasible as patients would know which drug they were on because of the side effects. And there was enough evidence presented to assuage the concerns about bias."

     

    Dr. Samuel Hunter, of Advanced Neuroscience Institute, wrote on his blog, "The FDA is on the “Naughty” list this year yet again for it’s handling of the biggest game-changing medication ever for MS. Absolute unbelievable ignorance. They voted the trials were inadequate and poorly designed (not a single expert believes this). The medication was twice as effective as Rebif, a standard of care medication."

     

    Despite the fact that the FDA staff reviewers presented a series of questions that were structured to elicit a negative vote on adequacy of trial design and the efficacy of Alemtuzumab over Rebif, the panel members of the Advisory Committee voted overwhelmingly that the sponsor, Genzyme, provided adequate evidence of effectiveness. The panel voted unanimously that, assuming efficacy results are as they appear, safety concerns should not preclude approval.

     

    The FDA should convene a new advisory panel composed of MS experts who have the perspective and judgment to render the appropriate advice for approval of this transformative
    medication. US patients deserve the right to choose the appropriate MS therapy in conjunction with their physicians. In addition, this FDA decision highlights serious inadequacies in the current process of drug approvals.

     

    Respectfully,

     

    Sheldon Robbins, M.D.
    29 Jan, 02:28 PM Reply Like
  • TimeOnTarget
    , contributor
    Comments (2172) | Send Message
     
    If this letter doesn't get Ms. Woodcock to personally take a very long, hard look at this issue, I don't know what would.
    29 Jan, 06:02 PM Reply Like
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