Xeris subcutaneous levothyroxine

[helvella]

Slow at getting round to noticing this article and then posting about it!

Given the numerous issues due to oral levothyroxine (whether solid or liquid), like tolerability, effects on gut, absorption, interference with food, drink, supplements and medicines, severe spiking of blood levels, and on and on, the idea of another approach to delivery is possibly huge news.

Of course, it will take years to really reach the market. It will be more expensive. Few medics will prescribe it (at least to begin with). And so on.

But we have to be pleased that at least one part of the pharmaceutico-medical establishment is recognising that there are issues.

Xeris gets green light to take subcutaneous challenger to AbbVie drug into phase 2

By Nick Paul Taylor

Dec 20, 2022 07:55am

Xeris Biopharma has the green light to take its subcutaneous levothyroxine into phase 2. After talking to the FDA, the company outlined plans to start a midphase trial of the investigational alternative to oral hypothyroidism therapy in the second half of next year.

Chicago-based Xeris applied its formulation technology to levothyroxine in light of evidence of the issues patients face when taking the thyroid hormone replacement therapy orally. According to Xeris, “the complexity of maintaining biochemical and clinical euthyroidism in patients undergoing treatment with oral levothyroxine cannot be underestimated.”

The company quoted evidence that nearly 40% of patients are either over- or under-treated because of factors related to formulation, use of the drug with food, adherence, use of concomitant medications and preexisting conditions. Many patients fail to reach target hormone levels. Increasing the dose can “cause a clinically meaningful shift in pharmacological effects” because of the narrow therapeutic index.

Xeris generated evidence that its subcutaneous formulation, XP-8121, may overcome some of the issues of oral levothyroxine earlier this year when it reported top-line data from a phase 1 clinical trial. The trial linked XP-8121 to slower absorption, lower peak plasma and higher extended exposure than AbbVie’s oral levothyroxine product Synthroid PO at a comparable dose. The results have teed up further trials.

Rest of article openly accessible here:

fiercepharma.com/pharma/xer...

[RedApple Administrator]

Whatever else, I like this bit:

"evidence that nearly 40% of patients are either over- or under-treated because of factors related to formulation,"

and

“the complexity of maintaining biochemical and clinical euthyroidism in patients undergoing treatment with oral levothyroxine cannot be underestimated.”

[helvella Administrator in reply to RedApple]

(Though I think they have fallen into the same language issue so many do, including me, of writing under-estimated but meaning over-estimated! It is so incredibly easy to under-estimate.)

[RedApple Administrator in reply to helvella]

Oh yes! I read under but my brain automatically translated to over!

[helvella Administrator in reply to RedApple]

We all do! Which was why I put my reply into parentheses trying to diminish its importance.

[Jaydee1507 Administrator]

So would that be a weekly or daily injection I wonder?

[helvella Administrator in reply to Jaydee1507]

Xeris sees the study establishing the average once-weekly dose and generating chronic safety data to support a planned phase 3 program.

I suspect that will be a barrier in the UK. On the one hand, unwilling to allow patients to self-adminster. On the other, unwilling to take on the burden of medical staff injecting weekly.

(Mind, Semaglutide/Ozempic/etc. might have helped forge a path through the self-adminstering issues.)

[RedApple Administrator in reply to Jaydee1507]

Being a wuss about such things, I'm not keen on the idea of having injections, especially not DIY! Hopefully they'll develop something we can just stick on our arm or wherever, that automagically stabs us (gently) with a predetermined dose every so often!

[Jaydee1507 Administrator in reply to RedApple]

I'm sure theres a fair portion of people who would'nt be keen at all on weekly injections. You wouldn;t be alone. Must be awful for someone whos hypo with the blood tests required even now.

I'd be fine with weekly DIY injections. Would save a daily chore.

[RedApple Administrator in reply to Jaydee1507]

Well I'm not panicking, it's years away from being a reality

[Jaydee1507 Administrator in reply to RedApple]

Maybe might happen late in our childrens lifetimes. Personally I would like to see that though.

[RedApple Administrator in reply to Jaydee1507]

An artificial gland somewhere (internal or external) that does exactly what our own thyroid should be doing would be a better solution. Pills and potions will be so 'last century'. 🤣

[helvella Administrator in reply to Jaydee1507]

The range of attitudes reported by member of the Pernicious Anaemia Society forum who self-inject is pretty extreme!

Some are horrified before they start but, of them, some eventually become blasé! While others become markedly less comfortable.

The ones who have had someone with lots of experience to literally hold their hand as the start clearly have an advantage.

[Jaydee1507 Administrator in reply to helvella]

I'm sure it wouldnt be mandatory initially anyway. Maybe over decades it might become the norm.