Drug fails in Phase II trial for treating Parkinson's Disease - Exenatide (Byetta, Bydureon)

[Baron1]

Evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, therefore the recent clinical trial warranted exploration of trying to attenuate pathogenic microglial function. They sought to test the safety and efficacy of NLY01—a brain penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation—in Parkinson's disease.

An investigation brain penetrant, pegylated analogue of the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide (Byetta, Bydureon) known as NLY01 did not lead to improvement in Parkinson's disease symptoms compared with placebo.

Neither 2.5 mg or 5.0 mg of weekly NLY01 injections showed any difference from placebo in the sum of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts II and III scores at 36 weeks, according to Andrew McGarry, MD, of Rowan University in Camden, New Jersey, and colleagues.

McGarry and co-authors randomized 255 people with early untreated Parkinson's disease to subcutaneous 2.5 mg or 5.0 mg NLY01, or placebo (85 people in each group). Participants were told to administer the drug or placebo once a week for 36 weeks. Mean age was 61.5 and more than half of participants were men.

The primary efficacy endpoint was change from baseline to week 36 in the sum of MDS-UPDRS parts II and III scores. Part II assesses motor aspects of experiences of daily living and part III is a motor examination. Each MDS-UPDRS sub-scale has a rating from 0 (normal) to 4 (severe).

Secondary endpoints included MDS-UPDRS part I scores (non-motor aspects of experiences of daily living), clinical and patient impressions of severity, cognitive test scores, and dopamine transporter imaging parameters. No secondary endpoint differed from placebo at either dose.

NLY101 was generally safe and well tolerated. Gastrointestinal disorders emerged in 61% of the 2.5-mg dose group and 75% of the 5.0-mg group, most frequently nausea.

Participants under age 60 showed nominally significant reductions from baseline in the sum of MDS-UPDRS parts II and III scores at 36 weeks compared with placebo, "a finding that could be driven in part by a greater decline in the younger placebo group," McGarry and colleagues acknowledged. "Further studies should look to test a younger population for potentially better treatment outcomes."

The phase II trial may have been too short to see effects clearly, the researchers noted. Exenatide-PD3, a phase III, 2-year study of exenatide in 200 people with mild-to-moderate Parkinson's disease on standard treatment, is underway; results are expected in 2024.

thelancet.com/journals/lane...

Best Wishes to all with your health and into the New Year,

Merry Christmas.

[JCRO]

Another likely wash out. When will we get some actual verifiable good news? Some actual disease modification from a drug new or old. Maybe the UK phase 3 throws up something of note. Maybe.

[kevowpd in reply to JCRO]

Probably never until the treatment arms are stratified into meaningful sub-populations. The best we can do right now might be to have:

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an LRRK group,

an SNCA group,

a PINK group,

and so on (other genetic groups)...

an idiopathic group with tremor dominant and no cognitive impairment

an idiopathic group with PIGD and no cognit impairment

Cognit impairment group

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Problem is that it's difficult to recruit enough trial participants in most of these buckets (besides the 5th and maybe the 6th rows above) to get a meaningful trial completed. It's also a comparatively new way of thinking about the condition (but something some high profile neuros like Albert Espay are focused on).

[PixelPaul in reply to JCRO]

If you’re holding out hope that there’s going to be anything in our lifetimes, don’t.

[Seamus6 in reply to PixelPaul]

Actually I disagree, there's a huge amount of research ongoing and I'm confident of something to slow or halt progression in my lifetime.It may turn out to be false/misplaced hope but I prefer that to no hope.

I have no intention of living a life without hope!

[MarionP in reply to JCRO]

Well it's premature, but it is good news actually, any news that increases our knowledge is good news. There is a longer-term trial apparently in process, but it's reasonable also to know when a door needs to be closed so the resources can move along toward doors that might yet open.

[Buckholt]

Levodopa works for most but is compromised by short half life, gastric emptying issues, competitive absorption problems and probably much else. I sometimes think that it may have been better to have spent the last decade or two spending the huge and mostly wasted resources on dead end therapies , perfecting the delivery of Levodopa instead

[SilentEchoes]

Thanks for sharing this. I'm starting Bydureon. We'll see how it goes.SE