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  • The FDA Nixes A Pathbreaking Drug For MS 33 comments
    Jan 16, 2014 9:16 PM | about stocks: GCVRZ, SNY

    Thirty developed nations have approved Lemtrada.

    The U.S. refusal to do so shows the need for regulatory reform.


    The Wall Street Journal, January 17, 2014

    Alemtuzumab is used today as an intravenous treatment for a form of leukemia. But 20 years of research centered at Cambridge University also has shown that the action of this drug-depleting immune cells that become misdirected and attack one's own body-is effective in treating multiple sclerosis.

    Under the brand name Lemtrada (a product of Sanofi and its U.S. subsidiary Genzyme), the drug has been approved in recent months for treating MS in 30 countries, including Canada, Australia and all members of the European Union. But on Dec. 27, Food and Drug Administration reviewers at the division level (subject to a final decision by top officials) rejected an application to use the drug here to combat MS.

    We are invested in Lemtrada through a partnership that one of us manages-and we still think the investment will do well. European authorities have called Lemtrada a "step change" in treating MS, and it will promptly become an important therapy at the intermediate "relapsing-remitting" stage of the disease. This is the stage when patients still have periods of normal life before permanent brain and nerve damage sets in.

    It was sickening to watch the FDA deny an obviously effective and important therapy to those afflicted with a terrible disease. For as long as the decision stands, much needless suffering will result (and much needless foreign travel). The agency's action is also a vivid example of the serious problems besetting U.S. drug regulation.

    The primary reason FDA reviewers gave for rejecting Lemtrada was that the studies demonstrating the drug's efficacy did not conform to the agency's standard requirement of double-blind, placebo-controlled drug trials-where some patients, unbeknownst to themselves and their doctors, receive placebo treatments. There are excellent reasons for the standard approach, but only up to a point. Lemtrada and many established MS treatments have immediate side effects, such as nausea and headaches, that are well known to doctors and patients. A double-blind trial would not really be blind. Patients on a placebo would promptly discover that they were the "controls," and many would decline to participate further-scrambling the statistical comparison with patients receiving real treatments.

    The Lemtrada investigators therefore designed "active control" trials that matched it against a leading MS therapy (a branded version of beta interferon) that would be its primary clinical alternative. The trials found that Lemtrada patients relapsed into active MS symptoms at rates 50% lower than patients taking the alternative. These results were buttressed by MRI and other objective measures that found, for example, highly significant reductions in brain atrophy and new brain lesions.

    FDA officials turned their backs on these powerful results. Drug regulators inhabit a complex world that mixes strong political pressures, abstract questions of biological science and statistical inference, and practical trade-offs between the benefits and risks of new therapies. In these circumstances, the agency elevated the double-blind, placebo-controlled trial to the level of dogma. It simplifies the reviewers' work and reduces the need to make case-by-case judgments about an appropriate trial design. Most of all, it leaves the agency with wide discretion, at the end of years of development and evidence, to say "no" or "tell us more."

    For Lemtrada, the FDA reviewers announced that the trials were not "adequate and well-controlled." They are now demanding another round of trials, with somewhat different procedures, that would take years and cost at least $100 million. Given the magnitude of the results of the already completed trials, the additional trials could add nothing to answering the regulatory question of whether Lemtrada is suitable for clinical use against MS.

    The Lemtrada application was one of a growing number of cases where progress in biological science is upsetting FDA doctrine. The drug was developed through decades of "clinical science" that combines scientific method with continuously recalibrated clinical treatments. The research, conducted by world-leading academic neuroscientists, encountered and solved many biological and clinical puzzles along the way, enlarging scientific understanding of MS's underlying mechanisms.

    By the time alemtuzumab entered regulatory review, its properties and effectiveness in treating relapsing-remitting stage MS were already well understood. In rejecting a therapy widely known to be highly effective, the agency's reviewers were sending a defiant message to the medical community: The advance of biological research and development must conform to FDA institutional prerogatives rather than the other way around.

    FDA reviewers raised an additional concern. Lemtrada, they said, presents serious health risks to patients that may exceed its health benefits. Lemtrada treats aberrations in the immune system, and that intervention does present risks, mainly of thyroid and blood disorders. But the risks of the drug are well known from the Cambridge research and from a decade of clinical use, in much higher doses, treating leukemia. In almost all cases when the disorders do appear, they are much less severe and more easily treated than MS itself.

    There is no reason to deny doctors and patients the choice of Lemtrada over other therapies that have risks of their own. For many with MS, the choice will be an easy one-as the fervent petitions of MS patients and advocacy groups during the FDA review attest.

    Lemtrada is administered just twice-in one-week intravenous regimens, one year apart-compared with established therapies that are administered continuously on a monthly, weekly or daily basis. And a significant number of Lemtrada patients find themselves free of MS debilities after just the first session. These are enormous benefits. Yet at a public meeting in November, one FDA reviewer warned an agency advisory committee that because Lemtrada patients would have less need to see their physicians constantly, it could be more difficult for physicians and the FDA to monitor them.

    This objection is revealing. At some point, regulatory command-and-control needs to make room for the welfare of patients and the skills and professionalism of their doctors.

    If Lemtrada does no more than postpone progressive, irreversible paralysis for a few years, permitting patients to live normal lives, that is a great blessing even if some of them fall off the FDA grid. But the therapy is also slowing the progression of the disease-some patients have remained free of clinical disease activity for up to 14 years.

    With experience and learning, these successes may point the way to averting MS damage to the central nervous system at the earliest, asymptomatic stages. Medical progress is iterative; it must be free to pursue the logic of the problem at hand at each incremental step.

    The cascade of Lemtrada approvals outside the U.S. demonstrates that vigilant public regulation can adapt to, and make use of, modern biological science. It should be adopted here. FDA reform will not be achieved in a single decision, but it will certainly require decisions, and correcting the stark mistake made about Lemtrada would be an excellent step in the right direction.

    Messrs. DeMuth are, respectively, a distinguished fellow at Hudson Institute and a managing partner of Rangeley Capital LP. Rangeley Capital invests in a Lemtrada-specific security that is publicly traded.

    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.

    Stocks: GCVRZ, SNY
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Comments (32)
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  • Philip Mause
    , contributor
    Comments (4327) | Send Message
    I wonder rather than just have a Heaven and Hell for drugs, we might also consider a Purgatory. Certain drugs approved in countries whose process is respected here could be made available on a limited basis to patients who would be given extensive information about the risks and the arguments concerning efficacy and would sign waivers. The patients would agree to be monitored to generate more information about the drug. There would be no Medicare reimbursement and insurance companies would generally not be required to provide reimbursement. And, with these limitations, patients with the approval of their physicians would be allowed to take the drugs in the United States.
    17 Jan 2014, 12:24 AM Reply Like
  • TimeOnTarget
    , contributor
    Comments (3679) | Send Message
    @Philip Mause --


    What a great idea. I genuinely like that-- a LOT.


    The only way I see that happening, however, would be legislative changes that direct that to happen in unambiguous terms. The FDA will have zero interest in that idea -- they would perceive it as robbing them of power and discretion (yeah, they will understand).


    Agencies can ignore common sense, good ideas, public opinion, etc. The one thing they can't ignore are their enabling statutes. Agencies are creatures of statute: They have no inherent powers, nor power to deviate from what the governing statutes direct them to do.


    So, if this is going to happen, it will involve getting Congress behind it, which brings up a whole new set of problems, cognitive biases, and human frailties.


    But, it is a genuinely good idea. I'd write a letter supporting it. Hell, I'd even stick a check in with my letter. Oh wait. They prefer cash these days . . . . .
    17 Jan 2014, 01:10 AM Reply Like
  • Philip Mause
    , contributor
    Comments (4327) | Send Message
    Thanks. I think that the key here is for this project to have a "Daddy" or a "Mommy" in the form of at lest one influential member of Congress who is dedicated to it and pushes it hard (and perhaps get his or her name on the bill). The first step might be for some of those with compelling cases of the disease who want to use the drug to contract Congressional offices. This could be a great project for the right Member.
    17 Jan 2014, 12:33 PM Reply Like
  • TimeOnTarget
    , contributor
    Comments (3679) | Send Message
    Philip --


    It would be. I think that an awful lot of people have been affected to some degree by the FDA's rejection of a drug or drugs. A significant number of people have been affected in a profound manner. It really would be something that attracted a lot of national attention.
    17 Jan 2014, 11:55 PM Reply Like
  • Philip Mause
    , contributor
    Comments (4327) | Send Message
    I think that an effort should be considered to organize the people affected and, if a number of them are in a Congressional district, make a contact. I think that this issue is one which the right Member might really run with.
    18 Jan 2014, 10:48 AM Reply Like
  • EnhydrisPECorp
    , contributor
    Comments (71) | Send Message
    This article should be a primer for any newbie biotech investor. Trying to predict what they FDA is going to do based on what they should do is a waste of time. Besides not sticking to previous SPA agreements, questioning methodologies that they previously agreed to in meetings, and giving oddball passes to some drugs with horrid clinical data, this is par for the course in my book.


    On a side note, there is a big push for "adaptive clinical" trials now. While this is still in the buzz word phase of its evolution, one concept that is catching on is the idea of active controls. Basically, you can't force all diseases, drugs, and therapies to conform to a universal norm. There needs to be wiggle room in clinical testing, not dogma.


    Anyways, great work!
    17 Jan 2014, 10:02 AM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (11787) | Send Message
    Author’s reply » Thank you; much appreciated. -C
    17 Jan 2014, 10:16 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Hi Chris,


    You say: "But on Dec. 27, Food and Drug Administration reviewers at the division level (subject to a final decision by top officials) rejected an application to use the drug here to combat MS."


    1. Do you know of any situation where top officials have reversed or voided a division level decision?


    2. Do you know of any forum to express one's disappointment at the FDA's Lemtrada decision directly to the FDA? Is there any way we can directly express our frustration with the FDA's decision? Letter writing? Emails? Etc.


    Thanks for your WSJ article! Your articles are greatly appreciated.
    17 Jan 2014, 08:50 PM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (11787) | Send Message
    Author’s reply » 1. Yes. Rare but happen.


    2. Yes.


    A letter to the WSJ would be helpful:

    Editor, The Wall Street Journal
    1211 Avenue of the Americas
    New York, NY 10036


    Additionally, you could comment directly to the FDA. One route would be to put comments regarding a citizen petition favoring reversing the decision here:



    You're welcome.
    17 Jan 2014, 09:46 PM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Here's an example of the FDA reversing a decision in April 2009:


    "FDA Reverses Decision Lets Powerful Painkiller Stay on Market


    Published April 10, 2009 /
    Associated Press


    The decision sounded reasonable. Pull 14 painkillers off the market because they had never received federal approval.


    These drugs might be unsafe, ineffective or of poor quality, the Food and Drug Administration said. It ordered that manufacturing cease within 60 days. Patients could use other painkillers that were already approved instead, they said.


    On Thursday, the FDA announced it had targeted one drug too many.


    Officials changed their minds about a form of liquid morphine that is given to perhaps as many as 2 million people at the end of life and dying at home. For these people, no substitute is available, the FDA learned from protesting doctors and patients.


    Just a few drops of the concentrated liquid, placed in the mouth of a patient who has trouble swallowing, lets a caregiver provide rapid pain relief.


    The FDA's Dr. Douglas Throckmorton said the drug would remain on the market until it's replaced by an approved version or some equivalent therapy.


    The reversal was welcomed by experts in hospice care and pain relief.


    Dr. Diane Meier, director of the Center to Advance Palliative Care at the Mount Sinai School of Medicine in New York, called Thursday's decision "fabulous.... It's incredibly refreshing and makes me hopeful about our government."


    The order has not changed for the other painkillers, at least for now, said Throckmorton, deputy director of the agency's Center for Drug Evaluation and Research.


    In interviews, experts said they didn't have firm numbers on how many patients use the concentrated liquid. But Meier estimated it may be at least 2 million Americans a year.
    20 Jan 2014, 12:31 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Here's another reversal but it took a year and a half:


    FDA Panel Backs Obesity Pill, Reversing Earlier Decision


    By Christine Hsu | Feb 23, 2012 12:03 PM EDT


    (Vivus Inc.) FDA Panel Backs Vivus' New Weight-loss Drug by a vote of 20-2. Qnexa is a once-a-day, proprietary, oral, controlled-release formulation of low-dose phentermine and topiramate, which is designed to decrease appetite and increase satiety (the sense of feeling full), the two main mechanisms that impact eating behavior.


    A federal advisory panel reversed an earlier decision on Wednesday voted 20-2 in favor of approving the experimental obesity drug Qnexa, propelling Vivus Inc’s pill closer to being the first prescription weight-loss medication in 13 years.


    Qnexa is a combination of the appetite suppressant phentermine and anti-seizure drug topiramate, both of which are already on the market and it was one of the three obesity drugs rejected by the U.S. Food and Drug Administration in the past two years over safety concerns.


    While Qnexa had met FDA success requirements for weight loss drugs, clinical trials had raised concerns about cardiovascular side effects and birth defects in babies whose mothers had taken it while pregnant, and in August 2010, the panel rejected the drug 10-6.
    20 Jan 2014, 12:39 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Another FDA Reversal:


    "Nov 25, 2013, 4:58pm EST
    FDA reverses course: Glaxo’s Avandia is safe after all


    Matthew Lloyd/Bloomberg
    GlaxoSmithKline, headquartered in London, heard good news on Monday when the FDA ruled that Avandia is safe to treat Type 2 diabetes.


    In a reversal of an earlier ruling, the U.S. Food and Drug Administration relaxed some restrictions on the prescribing and use of the diabetes drug Avandia, which is made by GlaxoSmithKline.


    Results from new tests show there is actually no elevated risk of heart attack or death in patients being treated with Avandia when compared to standard-of-care diabetes drugs, according to the FDA. Previous meta-analysis of clinical trials did show increased risk of heart attacks, but the latest announcement by FDA reverses those earlier findings.


    “Our actions today reflect the most current scientific knowledge about the risks and benefits of this drug,” said Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, in a statement accompanying the new ruling. “Given these new results, our level of concern is considerably reduced; thus, we are requiring the removal of certain prescribing restrictions.”


    GlaxoSmithKline (NYSE: GSK) released a statement late Monday confirming that the FDA had eased restrictions on patient access to the drug.


    “GSK welcomes the decision of the FDA and appreciates the Agency’s robust review of the science with regard to Avandia,” according to the statement. “GSK maintains its view that Avandia is a safe and effective treatment for Type 2 diabetes when used appropriately.”


    Avandia has been one of the more controversial drugs in recent memory. On July 2, 2012, GSK announced a $3 billion settlement in which it pleaded guilty to misdemeanor violations of the U.S. Federal Food, Drug and Cosmetic Act because it kept some information about the drug from the FDA, among other things.


    On Nov. 15, 2012, GSK agreed to pay $90 million to settle claims by 37 states and the District of Columbia under state consumer-protection laws regarding the marketing and promotion of Avandia.


    The drug had annual sales in the billions, but those dwindled to nearly zero as the drug was no longer sold in Europe and in only a handful of cases in the United States. For the time being, restrictions continue in place as GSK works with the FDA to implement its recommendations. A spokeswoman said she could not speculate on future sales or marketing strategy.


    FDA officials anticipate that the new indication will state “that the drug may be used along with diet and exercise to improve control of blood sugar in patients with type 2 diabetes mellitus, an indication similar to other diabetes drugs currently available,” according to the ruling."
    20 Jan 2014, 12:50 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    One more reversal:


    I like the part where they say:
    "This triggered a huge outcry from doctors and patients. As a result, the FDA reversed the decision, now allowing FMT to be used to treat C. diff without applying for an IND."


    Q: My 78-year-old father developed drug-resistant C. diff and almost died from diarrhea and dehydration. He received a stool transplant from his nephew, and it cleared up the condition quickly! So why is the Food and Drug Administration trying to restrict the use of it? I thought it was an accepted treatment. Can you explain?


    - Sally P., Richmond, Va.


    A: About 80 percent of people in the U.S. who battle chronic diarrhea and other problems caused by a Clostridium difficile bacterial infection are older than 65 - and often have been on antibiotics. C. diff can exist naturally in the gut, but taking antibiotics kills off other gut-dwelling bacteria that keep it in check. The result: The bad bacteria flourishes and causes chronic bouts of potentially lethal gastrointestinal distress. We know that fecal-microbiota-trans... (FMT) - transferring someone else's bacteria-rich stool into your digestive tract - can cure the infection 90 percent of the time. (There is some evidence FMT is also effective against ulcerative colitis and Crohn's disease, and some docs use it as a first-line treatment.)


    But this past February, the FDA decided FMT should be regulated as a biologic drug and doctors needed to apply for an investigational new drug (IND) application before performing the procedure. This triggered a huge outcry from doctors and patients. As a result, the FDA reversed the decision, now allowing FMT to be used to treat C. diff without applying for an IND.


    What the FDA had wanted to accomplish was a way to more carefully monitor the procedure and make sure that FMTs are safe and effective. While there are currently guidelines that call for screening of donors and donor stools for parasites, HIV, hepatitis, etc., more study is needed. So anyone considering FMT should make sure the doctor (and only a doctor) performing the procedure has experience doing it and follows the guidelines. And by the way, at least two drug companies are developing capsules of FMT's that can be as easily and safely used as probiotics, but we expect we're several years from that.
    20 Jan 2014, 12:55 AM Reply Like
  • Ruerd Heeg
    , contributor
    Comments (1328) | Send Message
    The article is dated 26 August 2013, so reversal of the decision regarding FMT took about 6 months?
    20 Jan 2014, 02:09 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    That's what it looks like. Next are two cases where the Secretary of Health and Human Services reversed an FDA decision! Looks a little lobbying might help Lemtrada.
    20 Jan 2014, 07:10 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Should the HHS Decision to Overrule FDA on Plan B Be Reversed


    Peter J. Pitts


    On December 7, 2011, Secretary of Health and Human Services Kathleen Sebelius overruled a decision of the Food and Drug Administration (FDA) on the over-the-counter (OTC) status of emergency contraception.


    What will be the repercussions of Secretary Sebelius’s action? Why is the act itself of far greater long-term significance than the transitory regulatory action it impacts?


    By reversing an FDA decision, the Secretary has set a dangerous precedent for all-comers to lobby Congress, the Department of Health and Human Services (HHS) and the White House on any and all FDA decisions—directly inserting politics into what must be a scientifically driven process.
    20 Jan 2014, 07:11 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Another example of the Secretary of Health and Human Services Kathleen Sebelius overruling an FDA decision (this is an editorial):


    "Editorial: FDA decision to reverse 'morning after' pill access is all about politics, not science


    Published: Wednesday, December 14, 2011, 6:48 AM


    By The Republican Editorials


    In a surprise move with election-year implications, the Obama administration's top health official overruled her own drug regulators and stopped the Plan B morning-after pill from moving onto drugstore shelves next to the condoms.


    When the Food and Drug Administration was trying to determine whether the morning-after pill should be made available without restrictions, officials were looking to answer two basic questions:


    1) Would it be safe for younger girls?


    2) Would those under 17 be able to understand how to use it?


    That’s it.


    The studies came back in the affirmative on both counts, and the FDA acted accordingly, moving to make the pill, which is used to prevent pregnancy if taken within 72 hours of unprotected sex, available without age limits, without prescription. Currently, the drug is available without a prescription only to those who are at least 17.


    But the FDA’s decision was quickly overruled by the secretary of the Health and Human Services Department. HHS chief Kathleen Sebelius said she made the move on her own, without direction from the White House.


    Well, maybe, but we’d doubt that she made the decision based solely on science. In fact, a senior White House official told The Washington Post that the administration had faith in Sebelius on both the science and the politics of the matter. Sebelius was formerly Democratic governor of Kansas, a conservative state. In that position, she doubtless learned when it was unwise to rock the political boat.


    We came to expect this kind of thing when George W. Bush was in the White House, when the line between politics and policy became so faint as to be often invisible. But when Obama was elected, we had hoped that science would win the day.


    “There is adequate and reasonable, well-supported, and science-based evidence that Plan B One-Step is safe and effective and should be approved for non-prescription use for all females of child-bearing potential,” FDA Administrator Margaret A. Hamburg said in a statement last week.


    Sadly, the science wasn’t enough."
    20 Jan 2014, 07:15 AM Reply Like
  • sts66
    , contributor
    Comments (3461) | Send Message
    No elevated risk my butt.....GSK greased the right palms to get Avandia expanded label or whatever......they spent $3B in fines and how much in settlements to families of dead patients but it doesn't actually increase risk? C'mon man, that doesn't pass the smell test! Another crooked FDA decision.


    BTW, your VVUS example ain't one - they received a CRL after the first attempt at approval, got a yes vote the second time around, same as ARNA. A CRL is not a "No" vote, it's a "we need more data" vote.
    25 Jan 2014, 01:06 PM Reply Like
  • Roxieanne
    , contributor
    Comments (1049) | Send Message


    My brother, deceased now, went for years not diagnosed with MS until he collapsed teaching his math class at the age of 45.


    He was rushed to the University hospital in Richmond. That is when a doctor at the University level saw him and diagnosed the disease.


    The only treatment was Steroids. ( He had previously been in Texas with no diagnosis from doctors there but not understanding what he had.)


    Another therapy has been floating for years as a substitute for insulin delivery by GNBT with their insulin by mouth, not needle ----- had to do trials in India as I recall. Still not approved.


    This is the kind of rules and regulations that stop progress. Imagine if Dr. Salk had not found the vaccine for polio and moved rapidly with Vaccines


    We lined up to get our shots, not being sure if they would work. Swimming pools were closed for the summer, we did not eat peaches coming from the Carolinas -----yet two of my best friends and a cousin ended up at Mayo Clinic in the Iron Lungs.


    All survived and became extremely productive people.


    Yes on the articles-----and some advocacy from the research hospitals.


    9 Apr 2015, 10:44 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Oops! Looks like they are the same situation
    20 Jan 2014, 07:30 AM Reply Like
  • User 11552471
    , contributor
    Comment (1) | Send Message
    The investors and authors conveniently "forgot" to mention that the drug was taken of the market as approved for leukemia purely and simply out of greed.
    I leave the readers to judge the ethics of doing it, particularly those who use the heavy ammunition against the FDA harming poor patients.
    20 Jan 2014, 11:50 AM Reply Like
  • TomLaney
    , contributor
    Comments (2) | Send Message
    This comment is revealing. Notice how those who support the FDA could care less about the well-being of individuals, and mock those individuals ("poor patients") who are victims of the FDA's coercion.


    At the same time we see the real reason these people support the FDA: hatred of free-markets ("greedy companies"). If a company takes a drug off the market, these people scream bloody murder, as if some moral offense has been committed, but have no problem with the thousands of deaths (and this is a conservative estimate) that the FDA causes.


    BTW, the FDA already outlaws Alemtuzumab for certain types of leukemia even though doctors know that it is highly effective. Also, we don't have private pharmaceutical companies. They are all heavily regulated and must pander to government in order to get their drugs on the market. The decision to remove Alemtuzumab from the market was, in part, due to pressure from the FDA.
    21 Jan 2014, 02:18 AM Reply Like
  • TomLaney
    , contributor
    Comments (2) | Send Message
    I agree with the author, but we should question the fundamental problem with the FDA: it is force used against individuals. The FDA, by it's nature forces individuals and their doctors to act against their own judgments. This is evil, regardless of how "scientifically sound" the FDA rulings are. Individuals have a right to their own life.


    "The cascade of Lemtrada approvals outside the U.S. demonstrates that vigilant public regulation can adapt to, and make use of, modern biological science."


    But how? Regulation is the opposite of science. Science is knowledge; science uses facts and persuasion. If you don't agree with the science, you're free to make your own decisions. Regulation, however, is force. The FDA does not make suggestions, it forces its will on patents and doctors, regardless of what these individuals believe and value. No amount of science will reform an agency that is fundamentally anti-science (i.e., force.)


    "At some point, regulatory command-and-control needs to make room for the welfare of patients and the skills and professionalism of their doctors."


    At some point?! "make room?!" So it's okay to harm _some_ patients and doctors some of the time? In the name of what, exactly? Who's lives do these individual's belong to, anyway? What kind of "welfare" can be attained at the price of a patient's control over his own life?


    "FDA reviewers raised an additional concern. Lemtrada, they said, presents serious health risks to patients that may exceed its health benefits."


    According to whom? By what right does the FDA get to decide what risks and benefits individuals want for themselves? It is pure evil to and a violation of an individual's right to life to prevent them from acting on their own values and judgments.
    21 Jan 2014, 02:17 AM Reply Like
  • sts66
    , contributor
    Comments (3461) | Send Message
    ""FDA reviewers raised an additional concern. Lemtrada, they said, presents serious health risks to patients that may exceed its health benefits."


    According to whom? By what right does the FDA get to decide what risks and benefits individuals want for themselves? It is pure evil to and a violation of an individual's right to life to prevent them from acting on their own values and judgments. "


    I believe political pressure via Obamacare's demand to reduce the cost of health care is creeping into FDA decisions - insurance, likely Medicare for a lot of MS patients, must pay to treat those side effects even though in the long run they'd likely save money on less MS drugs/treatments.


    This idea fits for their denial of AMRN's label expansion for the ANCHOR population, which would multiply the potential sales by a factor of 10 - FDA is claiming treating TGs 200-500 is medically unnecessary (BS), essentially interfering with patient/doctor decisions by denying access to a perfectly safe drug in Vascepa.
    25 Jan 2014, 01:12 PM Reply Like
  • EsotericPath
    , contributor
    Comments (124) | Send Message
    In my 25+ year career in the biopharma industry I witnessed from many vantage points within big pharma and multiple biotech companies the capriciousness of the FDA and the deterioration over that time of the FDA Committees from an evidence, science and medicine basis to more of a political and activist agenda. I was a co-founder of 2 biotech companies that were severely damaged by capricious FDA actions. One biotech was in a competition with a big Pharma to be the first drug to market and ran into an odd and difficult statistician at FDA who disagreed with all that biotech's outside experts on clinical data analysis and fought them tooth and nail causing a long delay that allowed the big Pharma to get to approval first and get first to market mover advantage by the time my biotech finally got FDA approval. The other biotech signed a contract with FDA with FDA agreeing to approve their drug after certain clinical studies were successfully completed. The studies were completed and the FDA reneged on the contract claiming they had new adverse side effect information about the drug from another company's data.
    Dealing with FDA is a lot like high school teachers and college professors that grade on final exams that contain questions and problems they never covered in class.
    IMO FDA will eventually approve the Genzyme MS drug after a few years of safety data from European patients on the drug. This goes back to FDA's thalidomide success in rejecting a drug that was approved in Europe.
    21 Jan 2014, 09:52 AM Reply Like
  • sts66
    , contributor
    Comments (3461) | Send Message
    "The other biotech signed a contract with FDA with FDA agreeing to approve their drug after certain clinical studies were successfully completed. The studies were completed and the FDA reneged on the contract claiming they had new adverse side effect information about the drug from another company's data."


    Are you saying they had a SPA that the FDA rescinded? Lots of AMRN supporting folks are looking for that information, previous SPA cancellations.
    25 Jan 2014, 01:14 PM Reply Like
  • EsotericPath
    , contributor
    Comments (124) | Send Message
    Yes. I cannot comment further on this. EP
    27 Jan 2014, 10:03 AM Reply Like
  • jacobtr
    , contributor
    Comments (855) | Send Message
    I spoke with two neurologists over the weekend on this topic. They haven't yet read the articles presented here on SA and the WSJ, but were highly skeptical that the FDA would reverse its decision. First, they agreed that the FDA is more concerned with protecting itself than providing new treatments for patients, but they also said there are a few new MS drugs out now so that there is little pressure to add one more. Further, the workings of MS are not well understood, so this makes efficacy more difficult to prove.


    It still looks like the CVR can pay out based on rest of world usage, so I'm not discounting the thesis, just adding what I've learned to the discussion.
    29 Jan 2014, 03:06 PM Reply Like
  • Chris DeMuth Jr.
    , contributor
    Comments (11787) | Send Message
    Author’s reply » They are almost certainly correct; thanks. -C
    29 Jan 2014, 03:28 PM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Hi Chris,


    Here's my my analysis of what I'd like to see from Germany w.r.t. sales of Lemtrada in Q1 in Germany. A good showing from Germany could be a god sign for future sales (what do you think?):


    In April, Sanofi will report the first quarter of Lemtrada revenue from Germany. These are the first sales that will count toward the First Sales Milestone of $400 million.


    What would be a good number?
    There are currently three groups of revenue that can contribute to the First Sales Milestone:
    1. Major Markets (excluding the US). Germany, France, Spain, Italy, and the UK
    2. non-Major Markets we know of that have approved Lemtrada: Canada, Australia, Mexico.
    3. non-Major Markets that we do not know that have approved Lemtrada: 29 countries that probably include some European countries like Belgium, The Netherlands, Switzerland, Luxembourg, Poland, etc.


    1. Major Markets:
    Germany's population is 82 million
    France's population is 66 million
    Italy's population is 61 million
    Spain's population is 47 million
    The UK's population is 63 million
    Total Major Market population = 319 million


    2. Non-Major Markets that we know of:
    Canada's population is 35 million
    Australia's population is 23 million
    (I am leaving out Mexico because it may be too poor to contribute much revenue)
    Total non-Major population = 58 million


    3. Some Non-Major Markets that we do not know of:
    Belgium's population is 11 million
    The Netherlands' population is 16 million
    Switzerland's population is 8 million
    Austria's population is 8 million
    Sweden's population is 9 million
    Total non-Majors we don't know of population = 52 million


    Total = 429 million
    Assume the MS population is evenly distributed..


    We need $400 total to reach the First Sales Milestone.
    Germany is 82/429ths of the total population = 19.1%
    In 4 quarters, Germany needs to bring in $19.1% of $400 million = $76.5 million.
    In 1 quarter, Germany needs to bring in 1/4 of $76.5 million = $19.1 million.


    We need to see Germany report at least $15 million in sales when they report Q1 sales in April, 2014.
    $15 million is good because:
    a) there are more countries contributing to the First Sales Milestone.
    b) The trend in sales is usually up.
    10 Feb 2014, 09:30 AM Reply Like
  • Ruerd Heeg
    , contributor
    Comments (1328) | Send Message
    This estimate is ok. It is better to do calculations based on MS patients, using MS prevalence numbers reported by scientists, disease registers or MS organisations. Chris did that in his article in December that is now exclusively available to SA Pro subscribers.


    For the major markets Chris used the following numbers of MS patients:
    UK: 100,000
    Germany: 130,000
    France: 60,000
    Spain: 42,900
    Italy: 68,000


    I have tried to make similar estimates including the non-major markets as well and with more detailed calculations.


    My article


    Based on my article and the table above $20 million is probably an estimate for the average quarterly sales in Germany (315 million divided by 4 divided by 4).
    10 Feb 2014, 09:47 AM Reply Like
  • sumikuboanr
    , contributor
    Comments (240) | Send Message
    Hi Ruerd, Thanks for your reply.


    1. I was actually trying to figure out what sales Germany NEEDED to have in Q1 2014 in order to determine if sales were on track to hit $400 and hit the First Sales Milestone. I wanted a sales number I could use to compare to the ACTUAL sales number for Q1 Germany that will come out in April 2014. That way I know if we have a good chance to reach the First Sales Milestone. If your estimate of average quarterly sales in Germany is $20 and my estimate is that we NEED $19 to reach the First Sales Milestone then it's a little more than 50/50 that we'll reach the First Sales Milestone.


    2. By the way, on the conference call they mentioned that 32 countries, other than the Major Market countries, had also approved Lemtrada. Do you know what those conuntries are?


    10 Feb 2014, 10:31 AM Reply Like
  • bigred2
    , contributor
    Comments (75) | Send Message
    What is the status of sales in the other major markets including France , Spain.and Italy ?


    I read that the still negotiating a price
    10 Feb 2014, 01:03 PM Reply Like
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