DWQA QuestionsCategory: QuestionsBezafibrate and CPT-2 deficiency
Ben asked 2 years ago
Hi,
I have CPT 2 deficiency, and I’ve been taking bezafibrate for almost 6 years as of today.
I understand that studies on bezafibrate are contradictory, but I decided to continue taking it because I think it is helping me.
Also, in-vitro, it was shown that when my fibroblasts were incubated with bezafibrate, fatty acid oxidation was (almost) normalized.
The daily dosage that was studied was 600mg a day. In my country, it used to be available in 200mg tablets, so I used to take 1 tablet 3 times a day.
Since about 3-4 years, it is now only available in SR 400mg tablets, so I usually take 1 tablet every 16 hours to reach a daily dosage of 600mg a day.

Let’s pretend that there was no doubt that bezafibrate 600mg a day was effective in CPT 2 deficiency. Does it make sense to take it every 16 hours, even though I’m not getting the same concentration of the drug reaching my blood throughout the day? Do you think I might still benefit from its ‘possible’ efficacy?

It is much simpler for me to take 1 tablet of bezafibrate SR 400mg every 24 hours. Do you think I might still get some benefit, if there is one, at a daily dosage of 400mg, or should I keep on taking 1 tablet every 16 hours?

Although potentially beneficial in short term, inducing mitochondrial biogenesis with bezafibrate worsened the metabolomic signature of mitochondrial disease, increasing FGF-21… since I’ve been taking for years, do you suggest measuring, monitoring metabolic biomarkers FGF-21, or others, to for possible toxicity? Which ones?

I’m hoping I could switch from bezafibrate to ren001 one day if there is some benefit, and if gets approved. I saw that there’s an ongoing phase 1 clinical trial. Is it possible to give a very rough estimation on how much time it would take for the drug to get approved, if nothing goes wrong?

Usually, how many years in general does it take for a drug to be approved, if it successfully passes all phases? Thank you!

1 Answers
Keith McIntire answered 2 years ago
This is a very complicated and difficult series of questions to answer, but I’ll try. First, there are no controlled trials to show efficacy or demonstrate optimal dosing of bezafibrate. (in fact, in the only blinded trial in an FAOD, patients with VLCAD deficiency did not improve disease symptoms.) Therefore, it is impossible to know how frequently to use it or how to transition from one form to another. I don’t use bezafibrate in my patients, though some have had it prescribed by other care providers. Understanding potential toxicities is an important aspect of any clinical trial, but without careful collection of data, it is also difficult to know what measures to follow to identify them. Finally bezafibrate and REN001 are very different drugs with completely different physiologic targets. It’s not possible to translate from one to the other. Dosing for REN001 if approved will ultimately be determined by the dosing used in the clinical trial. It is only entering an expanded phase 2 trial now, so it’s not really possible to know how long it will take to approval. 2-3 years is at least a reasonable guess (but it’s only a guess.) I hope this helps. Dr. Vockley