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Sarepta Therapeutics, Inc. Message Board

  • inventis inventis Jan 18, 2013 3:18 PM Flag

    More about Accelerated Approval

    Pretty straightforward description of Accelerated Approval from FDA website;

    Key word is surrogate marker: SRPT's 'green circles" dystrophin is their surogate marker. A competitor without being able to directly show dystrophin prodcution, from microscopic biopsy exam, as a surrogate marker would logically take longer to demonstrate an effect. The 6 MW minute walk test only confirms the surrogate marker.

    From FDA website: "The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious diseases, and that fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker that is used in clinical trials as an indirect or substitute measurement that represents a clinically meaningful outcome. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.

    Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as phase 4 confirmatory trials. If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug. If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.

    Captain Mary Kremzner: When it comes to treating serious or life-threatening diseases, speeding drug development and delivery is in everyone's interest. The Accelerated Approval Program is one way the FDA helps make new, potentially lifesaving drugs available more quickly. Hi, I'm Captain Mary Kremzner and this is Drug Info Rounds brought to you by the pharmacists in the FDA's Division of Drug Information. I'm joined by FDA pharmacist, Commander Catherine Chew, who will examine the Accelerated Approval process and what it means for the medical community. Cat, can you provide a little context about the origins and intentions of the program?

    Commander Catherine Chew: Absolutely. When starting a new drug, Mary, as you know it can take a very long time, oftentimes several years, to definitely demonstrate a clinical benefit and then go through the process of securing FDA approval. In 1992 the FDA instituted its Accelerated Approval Program as a way to speed new drugs to market that treat serious diseases and fill an unmet medical need.

    Captain Mary Kremzner: Now Cat, exactly how does the FDA determine when an expedited approval is warranted?

    Commander Catherine Chew: Generally drugs are approved under Accelerated Approval if they have the potential to impact factors, things like survival, day‑to‑day function or the likelihood of stopping a disease from progressing and becoming an even more serious condition.

    Captain Mary Kremzner: Now Cat earlier you mentioned filling an unmet medical need. How would you define that?

    Commander Catherine Chew: An unmet medical need simply means providing a therapy when none exists or providing a new therapy that may be superior to or less toxic than an existing one.

    Captain Mary Kremzner: So without the standard clinical outcomes how does FDA determine if a treatment is potentially effective?

    Commander Catherine Chew: Great question Mary. Accelerated Approvals use what we call a surrogate end point in clinical trials. These are markers or a physical sign of sorts used as an indirect measurement to predict a clinically meaningful outcome like survival or symptom improvement.

    Captain Mary Kremzner: So exactly how does the surrogate end point save time in the drug approval process?

    Commander Catherine Chew: Well for example, instead of having to wait to learn if a drug prolonged survival in cancer patients the FDA has approved drugs based on evidence that they shrink tumors. As a surrogate end point, tumor shrinkage is reasonably linked to real clinical benefit.

    Captain Mary Kremzner: Okay, so let me make sure I have this. Let’s say a drug goes through Accelerated Approval and gets to market, how do we know if it really provides that clinical benefit?

    Commander Catherine Chew: Any approvals given based on surrogate end points are on the condition that the sponsor will conduct post-marketing clinical trials to verify the anticipated benefit. If these trials, called Phase 4 Confirmatory Trials, shows the drug does in fact provide a clinical benefit then and only then does the FDA grant traditional approval for that drug.

    Captain Mary Kremzner: Worst case scenario, Cat, what if the drug fails to prove that clinical benefit?

    Commander Catherine Chew: In that case the FDA has a series of regulatory procedures in place that could eventually lead to the drug’s removal from the market.

    Captain Mary Kremzner: The Accelerated Approval Program strikes just the right balance between safety and speed which can make all the difference to patients with serious or life-threatening diseases. If you have questions about the Accelerated Approval Program, call or email the FDA’s Division of Drug Information."

    Sentiment: Strong Buy

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    • The 2012 new FDASIA law passed by congress in July, title IX: expanded the scope of products that qualify for accelerated approval.

      It addressed surrogate endpoints, expanding what data could be used as surrogate-- : "FDA may approve a new drug application for a serious or life threatening disease or condition based on a determination that the product has an effect on a surrogate endpoint ..reasonably likely to effect on irreversible morbidity or mortality. or other clinical benefit, taking into account the severity, rarity, prevalence of the condition and the availability or lack of alternative treatments.(the new law added morbidity mortality or severity etc.).. Such approval is referred to as Accelerated approval. The evidence that a surrogate endpoint can predict clinical benefit can include epidemiolgical therapeutic, or other biomarkers.. or other scientific tools. (The new law expanded these types of surrogate evidence.)

      Thus the new law appears to give more leeway in granting accelerated approval than the law prior to july 2012
      all imho no guarantee of accuracy

      Sentiment: Strong Buy

    • AA will happen............but i am making change until it does

    • nothing straight forward about Russell Katz

      im telling you there is a real fear out there among the smartest advocates out there. take nothing for granted

      • 2 Replies to starfe11
      • False assumption

      • Okay. Whoever is in his position has an important job to do, making sure snake oil doesn't get sold to the public, making sure drugs are safe. It is truly important, serious work. I don't envy anyone in that job.

        Being afraid is sort of irrelevant.

        The argument exists, logically, that if one only has 6 cases of a a trial experiment, nothing can be concluded until one has X cases, where X is some larger number. The existence of statistical inference means that X can be calculated. My understanding is that dystrophin production is completely proven, statistically, in this study with just a few cases. Also, the 6MW results, despite the small sample size, is statistically significant. As a physician, one needs to listen to the logic of science--which appears to support SRPT's case.

        Having a preconceived bias against small sample sizes is probably a good logical thing because that is how science and probabilites work; usually (BUT NOT ALWAYS) a small sample reveals nothing.

        SRPT appears to have an historic scientific result, with logic to support it.

        A prudent doctor at the FDA would love to be able to act prudently if the facts support it. Irrational bias is really beside the point.

        Sentiment: Strong Buy

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