[Bruce Black]

My wife has also been taking sodium phenylbutyrate plus TUDCA since January.  The phenylbutyrate is prescribed by her MGH neurologist, Dr. Ho, and comes from CVS Specialty Pharmacy, and we get the TUDCA from Amazon.  The doses are the same as what were used in the AMX-0035 trials, 6 grams of sodium phenylbutyrate and 2 grams of TUDCA daily, taken in divided doses AM and PM (6 tablets of sodium phenylbutyrate 500 mg and two capsules of TUDCA 500 mg in the AM and the same in the PM).  The phenylbutyrate is expensive but fortunately my wife’s insurance, Massachusetts BCBS Medicare Advantage PPO, is covering it, despite it being an off-label indication, and did not require a prior authorization.  (I’m guessing that many insurance plans may not cover it for an off-label indication, and I was suprised that it was so easy for us to get it covered.)  She is also taking riluzone and recently switched from Radicava IV infusion to the new oral suspension.  We have not noticed any adverse effects of any of these medications.  Under her insurance plan, these four drugs (sodium phenylbutyrate + TUDCA + riluzole + oral Radicava) are costing us about $22,000 per year, and would cost $280,000 without insurance coverage.   The insurance was covering the Radicava home infusions 100%, including the drug, all supplies, and any required nursing visits, with $0 copay.  Unfortunately, the oral form is covered under the part D benefit.  Since we have already passed the annual “catastrophic” cut-off, we are now paying $653 every 4 weeks (5% of $12,700) for the oral Radicava.  The TUDCA costs us $1,500 per year and the insurance does not cover it at all.  She also takes Tru-Niagen 300 mg twice daily, which has not been studied for ALS but was recommended by another friend who is an aging-brain research scientist.  This costs us another $800 per year.  (I am also taking TUDCA and Tru-Niagen, even though my 68 year-old brain seems to be entirely healthy as far as I can tell.)

As a “supplement”, TUCA is not FDA regulated, and the purity and dosing accuracy of supplements are notoriously unreliable.  (A laboratory study of 25 different over-the-counter preparations of St. John’s Wort some years ago showed that some contained no St John’s Wort at all and some had many times the stated dose.)  There are quite a few different TUDCA products available on the internet.  The Nutricost brand was recommended to us by a friend of a friend who is a leading aging-brain scientist at MGH/Harvard and takes it himself for brain health.  There are cheaper brands out there, but I think it’s worth a little extra money to have more confidence that we’re probably getting what we think we’re getting.

I see many testimonies in these forums that “this drug is helping me (or my loved one)” or “that drug is not helping me”.  Although that may be easy to determine with respect to medications for specific symptoms, like hyper-salivation, muscle spasms, or pain, it is probably nearly impossible to determine if any specific treatment is helping any specific individual with respect to the progression of ALS disease and disability.  The progression of the disease is too highly variable from one individual to another and even over time, the rate of progression is too subjective and difficult to measure, and there are no treatments yet that seem to have dramatic (i.e., very large) effects on the rate of progression or to halt or reverse the progression.  All we have to go one is that randomized, double-blind placebo-controlled trials of riluzole, Radicava, and the AMX-0035 combination seem to slow progression and prolong survival for individuals taking the active medication compared to placebo.  (My wife and I are both retired physicians.  We are not ALS specialists but we do understand how medical science works.)  The evidence seems to me to be stronger for some drugs than others.  My impression is that the evidence for AMX-0035 is much stronger than for either riluzole or Radicava.  We’re guessing that taking these three treatments may prolong my wife’s survival by 12 to 18 months.  On the other hand, given that ALS is probably many different diseases with a common symptom manifestation, and that all of the drug studies are too small to provide statistically meaningful breakdowns even between known disease subgroups (much less between different underlying pathophysiologies that we don’t even know about), it is quite possible that some PALS get no benefit from any of these treatments while others may get much more benefit than the study results seem to demonstrate.  (For example, if 50 PALS taking placebo in a given study survive an average of 12 months, while 50 PALS in a one subgroup take the study drug and survive an average of 24 months and 50 PALS in another subgroup take the study drug but receive no benefit and survive an average of 12 months, and we don’t have any way of identifying these subgroups, the study results will show that PALS taking the study drug survive an average of 6 months longer that the PALS taking placebo, and there will be no way of knowing that half the PALS got an extra 12 months and the other half received no benefit.)

[Bruce Black]

You may want to take a look at this youtube regarding the progression of ALS.  https://youtu.be/TMU-e3-2DWU

[Bruce Black]

The statement that sodium phenylbutyrate “is not covered by insurance” is not necessarily accurate.  My wife has been taking sodium phenylbutyrate since January 2022 and it has been covered by her insurance (Massachusetts BCBS Medicare PPO Blue ValueRx – a Medicare Advantage PPO plan), with copays as required fr all medications with this plan.  We did not need a prior authorization and in fact did not have to do anything at all to get this covered.  I would not be suprised if many insurance plans will not cover this or will require a prior authorization and then refuse to cover it for an “off-label” indication, but you should try to get it covered by your plan before assuming it will not be covered.