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Posted by on May 21, 2009 in Ethics, FDA, Neurology, Pharma

Follow-up: Insmed’s Development of Iplex in ALS

Follow-up: Insmed’s Development of Iplex in ALS

(For important background on this story, please see Tuesday’s initial post).

According to Insmed’s website, Tercica (comarketer of Increlex) and Insmed (sole manufacturer of Iplex) “plan to enter into negotiations concerning the development of IPLEX™ for the treatment of ALS.” Insmed writes that clinical development is contingent on data from Italian ALS patients who received (or are receiving) Iplex on a compassionate basis, as well as FDA requirements. At present, there are no clinical trials of Iplex in patients with ALS at the NIH database website.

Insmed also provides a summary of the first 2 years of the “Italian experience” with Iplex. According to the pdf, more than 500 patients, with various disorders, have been exposed to Iplex, most often at dosages ranging from 0.5-2 mg/kg/day. Insmed reports, “Positive effects on statural growth, insulin sensitivity, glycemic control, dyslipidemia, muscle strength, endurance, and functional abilities have been demonstrated [emphasis added].”*

In the Italian Expanded Access Program, subcutaneous Iplex (typically 1 vial or 36 mg) is being taken daily. Of 110 ALS patients (most of whom have advanced disease), 53 remain on treatment (at least at the time of the pdf draftthe date of which is not provided).

A total of 57 discontinued Iplex treatment (52% dropout rate): 34 died; 10 withdrew consent (1 due to an adverse effect, described as “muscle twitching”)**; for 6, the court order was annulled or expired or there was “logistic difficulty” with the program; 5 experienced an “unsatisfactory” therapeutic effect; and 2 were lost to follow-up.

Disease progression is being measured by the ALS Functional Rating Scale. Because there is no control population, the deterioration of the functional score can only be assessed and possibly compared to historical/natural-history data (although such a comparison is incredibly problematic, probably to the point of being useless). For what they’re worth, mean longitudinal scores are provided for 24 patients who completed 12 months of expanded-access nonblinded treatment (possible score range, 0-48).

Pretreatment

6 Months

12 Months

30.2 ± 7.9

27.8 ± 8.2

25.2 ± 7.8

Five patients discontinued Iplex as a result of possible treatment-related adverse effects: 1 case of nonserious “muscle twitching”; 1 case of fatal cholelithiasis and infection (patient had a history of gallbladder disease); and 3 cases of fatal cardiopulmonary arrest (1 patient had a history of hypertension and silent MI). The fatalities that were believed to be due to ALS (33) occurred at a time frame consistent with the known progression of the disease.

Insmed indicates that it is “working diligently” with the FDA to “make the necessary preparations” for the US clinical trial of Iplex. The company’s share price has risen sharply since the FDA provided expanded access to Iplex in March and okayed a clinical trial of the drug in ALS.

* Presumably Insmed means “or” instead of “and” in its description, unless all of the effects were demonstrated in each condition studied–which is highly doubtful.

** Which may well be a manifestation of ALS.

bmartin (1130 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.


3 Comments

  1. You state in your article that, “Because there is no control population, the deterioration of the functional score can only be assessed and possibly compared to historical/natural-history data (although such a comparison is incredibly problematic, probably to the point of being useless).”
    While I understand using historical ALSFRS progression decline is not “academically ideal” when compared to a matched sample or other means of comparing results, I am curious as to why you would call it “…probably…useless”? The typical decline is well documented (.8 point/month) and allows for real-world expediency when analyzing outcomes. So why would it not be used? Especially since it’s being used in other clinical trials in the US (e.g., Lithium).

  2. “…medicine is a business and industry and lags behind science anywhere from 50 to 200 years.” Radiologist, William Wassell, M.D.
    Wow. I just lost my sister two weeks ago from small cell lung cancer. She was diagnosed 9 months prior. As a writer/researcher, I quickly learned about the disease and its treatments… and a hell of a lot about this thing dubiously described as health care and aptly described as industry. I learned that the existing Stage IV protocol is a lucrative square dance with the cancer industry calling: Cancer. Chemo. Hospice… “Next”… Cancer. Chemo. Hospice…”Next”…
    So, not surprisingly, I ended up often more informed than the professionals, at least in areas experimental and/or proven outside the realm of “protocol.” Honestly, it was shocking how much exciting info is out there, and how few inside this world have the humility or curiosity to listen to anything other than Not Invented Here, i.e. the NIH, et al.
    What are we waiting for? According to a recent NY Times article, cancer research is stalled because it all about funding the status quo. The decades have encrusted research firms with bureaucracies and budgets. The article even quotes the head of NIH as saying: “…the system probably provides disincentives to funding really transformative research.” And existing trials? Can’t get the patients needed. Doctors won’t refer them. No money in a lost patient.
    Bottom line is: If you want to be your own guinea pig, it’s your life.
    Who is being protected by blocking access? That is the big question. One thing’s for sure, it’s not the patient with a death sentence.
    The fact that sick-care is in shambles is not necessarily entirely a bad thing. In desperation, Google and other research tools have democratized access into the hitherto secret and revered society of medicine. We are seeing a groundswell of emboldened patients and their caretakers–often more informed and willing to try cutting-edge care than their doctors, turned into advocates. This stuff is personal and they don’t give a damn about “academic” ideals when all hope is gone.
    Perhaps, we are seeing the end of medicine’s Dark Ages. Perhaps, this open access will affect a renaissance in research and quality of life much like the printing press expanded literacy beyond the priestly elite. Perhaps, doctors will start leaning forward instead of toward the door when we speak up. Perhaps we’ll actually cure something again like we did once upon a time with polio? Perhaps the US will once again lead in health care instead of its current position- one step ahead of Slovenia–at #30.
    The Gutenberg gave us the Protestant Reformation – where reading the bible for oneself, in the words of Martin Luther, meant “every man be a priest.” So to with Google, perhaps every man is becoming a doctor. If patients took an active and authoritative interest in their own health I doubt they’d fair any worse than m.d.’s and hospitals do now, with medical error accounting for one-third of all deaths. Trying to beat those odds is something some of us could live with, or at least die trying.