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Insmed Incorporated Message Board

  • zake1 zake1 Mar 17, 2013 9:02 PM Flag

    I'll start with this

    Amyotrophic Lateral Sclerosis (“ALS”) is defined as a rare or orphan disease because at
    any given time only 30,000 to 35,000 patients are alive in the United States, each with a
    life expectancy of two to four years from diagnosis. 5,000 to 6,000 persons are
    diagnosed with ALS in the United States every year, similar to the number diagnosed
    with Multiple Sclerosis (“MS”). The annual incidence of MS is 7000 to 8000, and the
    prevalence is 400,000.1 The difference? Those with ALS die and those with MS live
    many more years and thus receive a far greater proportion of research dollars. ALS is
    truly not a rare or orphan disease, even though there are less than 200,000 persons
    alive with the disease at any given time. Because diagnoses are often delayed and
    misdiagnoses occur, we believe that these numbers may be significantly underreported.
    Historically, the FDA has made efforts to address the challenges of developing effective
    clinical trials regarding therapies and treatments for ALS.
    Iplex, an experimental pharmaceutical, became available to the ALS community during
    the years 2009 to 2012 through an IND under the direction of the FDA and ALS
    WORLDWIDE. On July 1, 2009, FDA issued the following statement regarding access
    to Iplex:
    “FDA understands that ALS is a fatal disease with limited to no treatment
    options. We are very sympathetic to the desperate situation of patients
    with this terrible disease, and their families, and we remain committed to
    facilitating the development of effective drugs to combat ALS.
    The FDA is mindful of the need to strike a balance between access to
    unproven therapies for patients with limited treatment options, and the
    ethics of subjecting those patients to drugs with unacceptable risks or
    unconfirmed benefits.” 2
    This FDA mindfulness worked to good advantage in the instance of Iplex: the drug
    manufacturer was enlisted as a supporting agency; a small part of the patient
    community received access to a medication deemed potentially beneficial and of lesser

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    • Didn't Benjamin Byer take part in the original 2007 (less than two week program) of IPLEX treatment for ALS and be so moved by the positive experience that he documented his feelings in his movie production 'Indistructabe'. Ben Byer died of ALS back in 2008.

      Sentiment: Strong Buy

    • Didn't Debbie Gattoni (sp) (New Jersey resident) call IPLEX a 'miracle drug' after receiving less than two weeks supply of the drug in 2007 for her ALS.

      She also received it in 2009 as part of this small ALS advanced disease group.

      Sentiment: Strong Buy

    • harm than the further progression of ALS; it was done so under IRB supervised
      conditions and at minimal or no cost to the patients involved. Iplex remained available
      from 2009 to 2012 until the drug supply was depleted. Although IND patients derived
      symptomatic relief from Iplex, the pharmaceutical company was financially unable to
      conduct further clinical trials or continue manufacturing.
      On January 3, 2013, EMPOWER, the Phase III clinical trial of Dexpramipexole was
      determined by Biogen Idec to have failed because no ascertainable differences could
      be identified between the medication and placebo subjects administered in the trial.
      Until this time, Dexpramipexole was considered the most promising drug to ever
      emerge for the ALS patient community,
      Yet as stated by Biogen Idec,
      “The trial did not meet its primary endpoint, a joint rank analysis of function
      and survival, and no efficacy was seen in the individual components of
      function or survival. The trial also failed to show efficacy in its key
      secondary endpoints. Additional analyses of multiple subpopulations failed
      to demonstrate any efficacy among these groups. Based on these results,
      Biogen Idec will discontinue development of Dexpramipexole in ALS.” 3
      The failure of the Dexpramipexole Phase III trial, which showed notable promise and
      benefit in both the Phase I and Phase II clinical trials is the most recent in a long line of
      failed Phase III trials for the ALS patient community. 4
      But is it the failure of the drug or the failure of the trial construct that is at issue? ALS
      WORLDWIDE believes it is the trial construct that needs to be changed for the following
      1. ALS is, in all likelihood, not a single disease but rather a generic title given to a
      heterogeneous group of phenotypes or similar conditions. Cancer is a title given
      to many different diseases. In fact, there is not one form of breast cancer, but
      rather more than six different types of breast cancer, each requiring a different
      form of treatment based on the molecular signature of each tumor. 5
      2. ALS progresses through several, even many, disparate paths. One patient may
      have drop foot, another dysarthria and dysphagia, and yet another loss of upper
      peripheral limb strength and mass. Eventually, while all may end up in the same
      place, an ongoing quality of life can be best brought about through proper
      identification and treatment of each genetic or other molecular subgroup, as has
      been demonstrated in the treatment of cancer.
      3. The selection of clinical trial subjects who are symptomatic for less than 24
      months, as is now standard in ALS clinical trials, produces a group of patients,
      both those in medication and placebo groups, who will live longer than the duration

      • 2 Replies to zake1
      • On January 15, 2013, FDA/CDER, Small Business Chronicles offered an encouraging
        step forward in their paper, “Breakthrough Therapies:”
        “FDASIA (FDA Safety and Innovation Act) defines breakthrough therapy as a
        drug that is ‘intended, alone or in combination with one or more other drugs, to
        treat a serious or life-threatening disease or condition and preliminary clinical
        evidence indicates that the drug may demonstrate substantial improvement over
        existing therapies on one or more clinically significant endpoints, such as
        substantial treatment effects observed early in clinical development.’” 10
        This designation is intended to facilitate the development of new therapies, expedite
        review programs and grant access for drugs that meet safety and effectiveness

      • of the trial. Therefore, survivability as a criterion is without merit unless trials are
        carried out for years, which is currently untenable.
        4. Subgroups within this and other ALS clinical trials may have experienced benefit,
        and in some cases, significant benefit. Because the percentage of patients within
        the trials that experienced such benefit may be only 20 to 40 percent instead of a
        more robust 60 to 80 percent, entire trials may have been deemed as failures.
        5. Until now, little or no attention could be given toward the identification of common
        genetic and other molecular identifiers for subgroups that may experience trial
        6. It should be acknowledged that clinical trial benefit for ALS patients should include
        three evaluation subsets: a) bona fide improvement of symptoms; b) provable
        maintenance of symptoms; and c) reduced rate of decline of symptoms. Each of
        these subsets has independent value in determining efficacy.
        7. With more than 100 genetic permutations now known to affect both familial and
        sporadic ALS, pre-human testing of the SOD1 mouse continues to be an inelegant
        model for subsequent human treatment, frequently leading to false positives.
        These included minocycline, creatine, Celebrex, Neurontin, Lithium, arimoclomol,
        Myotrophin, pioglitazone, Copaxone, Olesoxime, xaliproden, Indinavir and
        ceftriaxone. With the current awareness of a less clear distinction between
        sporadic and familial ALS and the frequency with which positive SOD1 mouse
        trials have led to human clinical trial failures, it is also possible that false negatives
        may have existed. 6, 7, 8, 9
        On January 15, 2013, FDA/CDER, Small Business Chronicles offered an encouraging

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