Astonishing Parkinson's Treatment

[Hornius Emeritus 12462]

According to the BBC, this video is real.
 

Article:

https://www.bbc.com/news/articles/cd1xwr2qy3do

 

 

 

[troph 24798]

that's amazing.

[Dendox 102]

wow!  Proof is in the pudding!

 

And then you have this

 

https://www.morningstar.com/news/dow-jones/202406255931/fda-again-rejects-abbvie-parkinsons-drugpump-combo-update

 

 

[CooterBrown 18012]

3 minutes ago, Dendox said:

And then you have this

https://www.morningstar.com/news/dow-jones/202406255931/fda-again-rejects-abbvie-parkinsons-drugpump-combo-update

 

 

Abbvie is gonna have to do better...

[Bevo 13577]

Anyone see Awakenings starring Robin Williams?

[Chopper 17235]

It'll cost 30GBP at the chemist in London but 125,000USD at CVS. 

[Dennis Taylor 18825]

Sounds like they need better lobbyists 

[Anastasis 23469]

Yeah, that's a pretty cool before/after shot. Not really a new drug though, a new delivery mechanism (infusion) that smooths out the on/off effects. The active ingredients are basically the same as what PD has been treated with for decades (levodopa/carbidopa). Video is probably a bit misleading in terms of differentiating this from existing treatments. You can see the same short-term effects with administration of simple oral levo/carbidopa. The differentiator appears to the be the increase in on time and the reduction in off time over extended periods with the infusion. Balanced by greater frequency of side effects and side effect related treatment discontinuation. I think that the FDA eventually approves it as the hang up appears to be manufacturing. Would be more interesting to compare it head up to extended release orals and/or the GI administered form. The real advance here appears to be that compared to the GI infusion this doesn't require surgical placement. 

Findings

Between Oct 19, 2020, and Sept 29, 2021, of 270 participants screened and 174 enrolled, 141 were randomly assigned and received continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo capsules (n=74) or oral encapsulated immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution (n=67). Compared with levodopa-carbidopa, foslevodopa-foscarbidopa showed a significantly greater increase in on time without troublesome dyskinesia (model-based mean [SE] 2·72 [0·52] vs 0·97 [0·50] h; difference 1·75 h, 95% CI 0·46 to 3·05; p=0·0083) and a significantly greater reduction in off time (−2·75 [0·50] vs −0·96 [0·49] h; difference −1·79 h, −3·03 to −0·54; p=0·0054). Hierarchical testing ended after the first secondary endpoint. Adverse events were reported in 63 (85%) of 74 patients in the foslevodopa-foscarbidopa group versus 42 (63%) of 67 in the levodopa-carbidopa group, and incidences of serious adverse events were similar between the groups (six [8%] of 74 vs four [6%] of 67, respectively). The most frequent adverse events in the foslevodopa-foscarbidopa group were infusion site adverse events (erythema 20 [27%]), pain 19 [26%]), cellulitis (14 [19%]), and oedema (nine [12%]), most of which were non-serious and mild–moderate in severity. The only system organ class that had more than one serious adverse event in the foslevodopa-foscarbidopa group was infections and infestations (catheter site cellulitis [one [1%]] and infusion site cellulitis [one [1%]). Adverse events led to premature discontinuation of study drug in 16 (22%) of 74 participants in the foslevodopa-foscarbidopa group versus one (1%) of 67 participants in the oral levodopa-carbidopa group.

[Armybrat 40846]

Pretty interesting, as one of my brothers and a SIL were diagnosed with Parkinson’s in the past year.

[jimmyjazz 45955]

My mother-in-law recently died from Parkinson's disease.  Medications "helped", but the game changer for years was deep brain stimulation.  Basically, it was an electrical impulse repeatedly applied in the brain in exactly the right spot, powered by a device implanted in the chest cavity, much like a pacemaker.  We figure it bought her 10-15 years.

[B00M 6416]

1 hour ago, Hornius Emeritus said:

According to the BBC, this video is real.
 

Article:

https://www.bbc.com/news/articles/cd1xwr2qy3do

 

 

 

I gotta say, it looks like his morning Parkinson’s workout is keeping him in great shape

[Pam Cummings 9642]

[Deej 76791]

So we might just get a Back to the Future 4?

[Biff Tannen 45685]

1 hour ago, Deej said:

So we might just get a Back to the Future 4?

[TwiceHorn 31471]

6 hours ago, Anastasis said:

Yeah, that's a pretty cool before/after shot. Not really a new drug though, a new delivery mechanism (infusion) that smooths out the on/off effects. The active ingredients are basically the same as what PD has been treated with for decades (levodopa/carbidopa). Video is probably a bit misleading in terms of differentiating this from existing treatments. You can see the same short-term effects with administration of simple oral levo/carbidopa. The differentiator appears to the be the increase in on time and the reduction in off time over extended periods with the infusion. Balanced by greater frequency of side effects and side effect related treatment discontinuation. I think that the FDA eventually approves it as the hang up appears to be manufacturing. Would be more interesting to compare it head up to extended release orals and/or the GI administered form. The real advance here appears to be that compared to the GI infusion this doesn't require surgical placement. 

Findings

Between Oct 19, 2020, and Sept 29, 2021, of 270 participants screened and 174 enrolled, 141 were randomly assigned and received continuous subcutaneous infusion of foslevodopa-foscarbidopa plus oral placebo capsules (n=74) or oral encapsulated immediate-release levodopa-carbidopa plus continuous subcutaneous infusion of placebo solution (n=67). Compared with levodopa-carbidopa, foslevodopa-foscarbidopa showed a significantly greater increase in on time without troublesome dyskinesia (model-based mean [SE] 2·72 [0·52] vs 0·97 [0·50] h; difference 1·75 h, 95% CI 0·46 to 3·05; p=0·0083) and a significantly greater reduction in off time (−2·75 [0·50] vs −0·96 [0·49] h; difference −1·79 h, −3·03 to −0·54; p=0·0054). Hierarchical testing ended after the first secondary endpoint. Adverse events were reported in 63 (85%) of 74 patients in the foslevodopa-foscarbidopa group versus 42 (63%) of 67 in the levodopa-carbidopa group, and incidences of serious adverse events were similar between the groups (six [8%] of 74 vs four [6%] of 67, respectively). The most frequent adverse events in the foslevodopa-foscarbidopa group were infusion site adverse events (erythema 20 [27%]), pain 19 [26%]), cellulitis (14 [19%]), and oedema (nine [12%]), most of which were non-serious and mild–moderate in severity. The only system organ class that had more than one serious adverse event in the foslevodopa-foscarbidopa group was infections and infestations (catheter site cellulitis [one [1%]] and infusion site cellulitis [one [1%]). Adverse events led to premature discontinuation of study drug in 16 (22%) of 74 participants in the foslevodopa-foscarbidopa group versus one (1%) of 67 participants in the oral levodopa-carbidopa group.

I'd be interested to see the patent situation here.

As you note, C/L is a standard, old treatment, so I'm sure the chemical composition with efficacy patents are long expired.  There may be something chemically/pharmacalogically new about this variant, though.

That may leave dosage patents and the infusion machine, to the extent there's anything patentable about that.  Patents or no, Abbott is going to get 6 years of exclusivity upon approval.

Edited August 29 by TwiceHorn

[Anastasis 23469]

2 minutes ago, TwiceHorn said:

I'd be interested to see the patent situation here.

As you note, C/L is a standard, old treatment, so I'm sure the chemical composition with efficacy patents are long expired.

That may leave dosage patents and the infusion machine, to the extent there's anything patentable about that.  Patents or no, Abbott is going to get 6 years of exclusivity upon approval.

My understanding after reading a bit is that active ingredients are highly soluble prodrug formulations (after absorption the body metabolizes the prodrug foslevodopa into the drug levodopa by chopping off the "fos"). So not exactly the old treatment, but with just a very minor molecular tweak to make the subcutaneous infusion viable. Not sure how any of that shakes out wrt the patents. It's a $62k/year drug in Canada. Not sure what pricing concessions NHS got, but it would probably be in the six figures range in the US. 

[hpslugga 4058]

11 hours ago, Deej said:

So we might just get a Back to the Future 4?

 

[TwiceHorn 31471]

8 hours ago, Anastasis said:

My understanding after reading a bit is that active ingredients are highly soluble prodrug formulations (after absorption the body metabolizes the prodrug foslevodopa into the drug levodopa by chopping off the "fos"). So not exactly the old treatment, but with just a very minor molecular tweak to make the subcutaneous infusion viable. Not sure how any of that shakes out wrt the patents. It's a $62k/year drug in Canada. Not sure what pricing concessions NHS got, but it would probably be in the six figures range in the US. 

I did find what seems to be the basic patent for the composition. https://patents.google.com/patent/US20190224220A1/en

What's interesting is that that one there was allowed, but instead of letting it grant, they have filed four continuations, none of which have been granted.  And each of them has a non-publication request, so are unpublished, meaning the public and competitors can't see what they're doing with the coverage.

The earliest filing date of that family is 2017, so all patents would expire in 2037 or thereabout.  So this strategery I guess delays grant until something closer to marketing in the US, but has also eaten seven years of term, or half of it.

But I guess they're going to get some of that back due to Patent Term Restoration. https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/small-business-assistance-frequently-asked-questions-patent-term-restoration-program

I saw they charge 85GBP for a vial (a month's supply) in the UK, before discounts etc.  Don't see what they charge for the pump.

 

Edited August 29 by TwiceHorn

[Anastasis 23469]

22 minutes ago, TwiceHorn said:

I saw they charge 85GBP for a vial (a month's supply) in the UK, before discounts etc.  I would hope that the pump is free at those rates. 

 

A day's supply. The vial is single use and expires after 24h. Max dose is two and a half vials per day. So anywhere from let's call it $40-80k per year. Plus the hardware. 

[TwiceHorn 31471]

5 minutes ago, Anastasis said:

A day's supply. The vial is single use and expires after 24h. Max dose is two and a half vials per day. So anywhere from let's call it $40-80k per year. Plus the hardware. 

Yeah not sure where I got the "month's supply" re-reading,  Just says 85gpb for a vial.  Yikes

[TwiceHorn 31471]

Also thought I would look at their European Patent.  It appears they only sought patents in US, EU, and JP.  

One of the biggest knocks on the US system is that you can file endless continuation applications, which are all the same application, but with different claims (sometimes to markedly different subject matter, sometimes not).  Regardless, continuations themselves do not extend patent term, they all expire on the same day, 20 years from filing of the first application.  In a lot of senses, a "family" of continuation patents can be regarded as one big patent.

The EU and most other jurisdictions don't allow that.  But Abbott let the first European Patent application, corresponding to the above, die on the vine, and have filed a "divisional."  A divisional is allowed when an Office tells you you are claiming more than one invention in an application, that is, you have claims to a composition, a dosage, etc.  Each would be regarded as a different invention and you have to file a second, third, etc. to seek the other types of claims/inventions identified.

So, shenanigans have ensued.  The biggest booger in the US is the Patent Term Restoration act, which treats drugs and devices subject to approval differently than everything else.  The maximum attainable term is supposed to be 14 years from approval.

[Anastasis 23469]

20 minutes ago, TwiceHorn said:

So, shenanigans have ensued. 

Unsurprising for Abbvie.

https://www.nytimes.com/2023/01/28/business/humira-abbvie-monopoly.html

How a Drug Company Made $114 Billion by Gaming the U.S. Patent System

AbbVie for years delayed competition for its blockbuster drug Humira, at the expense of patients and taxpayers. The monopoly is about to end.

By Rebecca Robbins

Jan. 28, 2023

In 2016, a blockbuster drug called Humira was poised to become a lot less valuable.

The key patent on the best-selling anti-inflammatory medication, used to treat conditions like arthritis, was expiring at the end of the year. Regulators had blessed a rival version of the drug, and more copycats were close behind. The onset of competition seemed likely to push down the medication’s $50,000-a-year list price.

Instead, the opposite happened.

Through its savvy but legal exploitation of the U.S. patent system, Humira’s manufacturer, AbbVie, blocked competitors from entering the market. For the next six years, the drug’s price kept rising. Today, Humira is the most lucrative franchise in pharmaceutical history.

 

[TwiceHorn 31471]

25 minutes ago, Anastasis said:

Unsurprising for Abbvie.

https://www.nytimes.com/2023/01/28/business/humira-abbvie-monopoly.html

How a Drug Company Made $114 Billion by Gaming the U.S. Patent System

AbbVie for years delayed competition for its blockbuster drug Humira, at the expense of patients and taxpayers. The monopoly is about to end.

By Rebecca Robbins

Jan. 28, 2023

In 2016, a blockbuster drug called Humira was poised to become a lot less valuable.

The key patent on the best-selling anti-inflammatory medication, used to treat conditions like arthritis, was expiring at the end of the year. Regulators had blessed a rival version of the drug, and more copycats were close behind. The onset of competition seemed likely to push down the medication’s $50,000-a-year list price.

Instead, the opposite happened.

Through its savvy but legal exploitation of the U.S. patent system, Humira’s manufacturer, AbbVie, blocked competitors from entering the market. For the next six years, the drug’s price kept rising. Today, Humira is the most lucrative franchise in pharmaceutical history.

 

It looks like what they did is treat an NDA as an act of infringement, which is a thing, like Patent Term Restoration, only available to pharma.

And, it's not just Abbott. It's errbody.  I am unaware of any pharma the doesn't "game the system."

Pharma patentees are somewhat disadvantaged because the FDA approval process could prevent marketing and selling (and profiting and recoupment of costs), until well into the 20 year patent term, depriving pharma of the rights more or less available to everyone else.

But the compensations we have in the system, restoration and shit like an NDA is an act of infringement, seem to have gone overboard.  Also, the grant of exclusivity by the FDA upon approval, patent or no, seems extravagant. https://www.fda.gov/files/drugs/published/Exclusivity-and-Generic-Drugs--What-Does-It-Mean-.pdf

Edited August 29 by TwiceHorn