Aug 312015
 

The interest level and expectations surrounding BYM338 are evidenced here.

The interest level and expectations surrounding BYM338 are evidenced here.

All of us with inclusion body myositis are waiting anxiously for some sign of results from the Novartis BYM338 trials. After all, until now there has been no proven treatment available for this relentlessly progressive muscle wasting illness. The critical stage III worldwide trial is wrapping up later this year and so far all we have are anecdotal remarks from participants. Of course they can only guess because the study is blind, with a fourth of the participants getting a placebo and another fourth getting a dose that is very low. The good news is that some people are reporting results that to them seem significant enough they believe they must be getting either the middle or highest dose and it is working.

However there are places we can look to find real data. For example, a study report published in Current Rheumatology Reports and made available through Springer.com contains some actual results from the phase IIa trial on patients. This was a small trial of 14 participants and of them 11 received the drug. It states that the participants who received the drug were given a dose of 30 mg per kilogram of body weight in a single infusion. The results were then measured at two months and again at three months. After two months, the average person receiving the drug gained about 7 percent of thigh muscle volume. Walking distance in six minutes was measured another month later and the average drug recipient gained 15 percent in walking speed. Both results were statistically significant. The dose was three times greater than the maximum dose being used in the current stage IIb/III dose-finding trial, (although it was only a single dose while the trial consists of monthly doses.) According to the Brookings institute, these results were what prompted the FDA to grant Breakthrough Status to BYM338.

The results of an early study of BYM338 are reported here.

The results of an early study of BYM338 are reported here.

Another place we can look to obtain hints about the success of BYM338 is in the other trials that Novartis has been conducting. The ClinicalTrials.gov website lists eight studies that have been completed or are ongoing plus one that was withdrawn. Among the conditions for which the drug is being tested are IBM, sarcopenia, and cachexia related to chronic obstructive pulmonary disease, lung cancer and pancreatic cancer. Sarcopenia is the skeletal muscle wasting that occurs in most people beginning at age 30 and accelerates as we age. It is classified as an illness when the muscle wasting exceeds two standard deviations from the norm. Cachexia is the wasting of muscle plus fat that results from many serious illnesses. Considering the high cost of conducting all these trials, it is clear that Novartis has high hopes for the drug. As do we!

Questions:

1. In the Novartis quarterly report presentation for Q2 of 2015 they continue to state that FDA submission of BYM338 for sporadic inclusion body myositis will be in 2016. My physician was told by Novartis that they were accepting no requests for compassionate use for this drug prior to FDA approval. Might that policy change once the submission to FDA has been made? (Compassionate use, also called extended use, is an FDA program to make drugs available to seriously ill patients when no other medication is available. FDA states that compassionate use is available for drugs that have not been formally approved nor proven effective, so it is a mystery why Novartis has chosen to withhold this particular drug from the program.)

2. As I understand the mode of action of BYM338, it prevents myostatin from signaling muscle cells to stop growing. This allows the cells to resume their normal process of regeneration (myogenesis). Although it doesn’t cure the IBM, it hopefully will allow the body to build new muscle cells as fast or faster than IBM destroys them. Of interest to those of us where the disease process has resulted in near paralysis, how much muscle fiber must be remaining for myogenesis to take place?

3. The trial with mechanically ventilated patients was withdrawn. Does this mean there was some side effect related to mechanical ventilation? Unfortunately, some IBM patients may become too weak to breathe without mechanical assistance.

  8 Responses to “BYM 338: What We Know and What I Wonder”

  1. Great piece, Mike! Be sure to post a link to this on the TMA Community Forum. Thanks for all the insightful work you do.

  2. Thank you so much for breaking this down. I appreciate all of your efforts in keeping us informed.

  3. Thank you very much Mike for posting this exceptional summary of where we stand at this point. You are a very classy individual!! This is so beneficial for fellow IBM patients like ourselves.

  4. This May the FDA published a piece on the “breakthrough” designation given to BYM338. It includes an interesting discussion of the new treatment. Here is a link to the piece: http://google2.fda.gov/search?q=bym338&client=FDAgov&site=FDAgov&lr=&proxystylesheet=FDAgov&requiredfields=-archive%3AYes&output=xml_no_dtd&getfields=*

  5. Thank you Mike. Keep sending good info and take care

  6. Thank you for this excellent bit of sleuthing. Given the published outcomes and the small number of AEs the is no humane reason not to provide Bimagrumab to qualified physicians on a “Comapssionate Use” basis. Most likely Novartis is afraid of some idiosyncratic sponge that would then have to be reported to the FDA as a side effect, delaying approval. I think if enough of us asked and perhaps put a bit of political pressure on them the story would change. I remember the early days of the AIDS epidemic when massive political pressure, rallies, demonstrations were reported and the FDA relented and gave INDs to individuals for many experimental drugs.

    Why not? We all know our eventual fate with this disease and I am willing to give BYM338 a try.. Nothing to lose. I am beginning to explor ways to get at both the FDA and Novartis thru my representatives. If we all did that pressure would build. I have a FOIA request in with the FDA. I want to find out if ANYBODY got BMY 338 on compassionate use basis. I am certain that if the CFO of Novartis had a nephew with sIBM he would get the drug.

    I’m not gonna sit back an wait!

    Peter

  7. Peter – A few questions:

    Could you explain what a FOIA request is? What was the process for getting an FOIA request in with the FDA? Lastly, when you refer to your “representatives” are they political representatives (House or Senate). — Thanks in advance for your answers to my questions.

    — MMS

  8. I have sIBM and have called the FDA. I could have the drug bym338 if the manufacter would provide the drug. Novartis refused to provide the drug. I have seen the drug for 1,000 dollars a gram on line in China. I don’t know if that is the black market or what, but with that you probably don’t know what you are getting.

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