Tag: Roche

At last: Selnoflast

~ Simon ~ 10 Comments

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One of the most common questions I get from SoPD readers is what’s new with inflammasome research? Another version of this question is where are the clinical trials for NLRP3 inhibitors in Parkinson’s?

Readers have become very enchanted by this new class of anti-inflammatory drugs as a potential future treatment for Parkinson’s – and there is preclinical evidence to support this vibe. But the  clinical development of these experimental therapies has been slow. 

Recently, the pharmaceutical company Roche has initiated Phase 1b testing of their NLRP3 inhibitor (called Selnoflast) in people with Parkinson’s – the first in this class. 

In today’s post, we will discuss what the inflammasome is, how NLRP3 inhibitors work, and what the new clinical trial involves.

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On the 21st September 2020, the website for an Ireland-based biotech company called Inflazome suddenly disappeared. In its place was a single page, that stated the large pharmaceutical company Roche had purchased the biotech firm and taken on all of its inflammasome-targeting intellectual property (Source).

This was a big deal for folks who were watching the inflammasome research world. It suggested that the big players (pharma) were now interested in this space ($449 million interested in the case of Inflazome). And since then, there has been a rush of other pharma companies buying or developing inflammasome-targeting agents.

The Inflazome purchase was also interesting because the company was targeting Parkinson’s as one of their indications of interest.

And it would appear that Roche is now following up on this interest, having initiated a clinical trial program focused on inflammasomes in Parkinson’s.

Hang on a second. Remind me, what are inflammasomes?

Continue reading “At last: Selnoflast” →

When Inflazome becomes Roche

~ Simon ~ 12 Comments

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Over the past two decades, pharmaceutical companies have shifted from maintaining large in-house drug development platforms to a model that involves acquiring small biotech firms with interesting agents once those companies reach a certain point in their maturation.

This week a biotech firm called Inflazome was bought by the big pharma Roche.

Inflazome has been developing a novel NLRP3 inhibitor, which targets inflammasome activation and the company has had Parkinson’s in it’s sights as far as indications of interest.

In today’s post, we will discuss what the inflammasome is, how NLRP3 inhibitors work, and what will be happening next.

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Source: Science

One of the hottest areas of Parkinson’s research world is ‘inflammation‘ (cheesy pun intended).

What is inflammation?

When cells in your body are stressed or sick, they begin to release tiny messenger proteins which inform the rest of your body that something is wrong.

When enough of these messenger proteins are released that the immune system becomes activated, it can cause inflammation.

Inflammation is a critical part of the immune system’s response to trouble. It is the body’s way of communicating to the immune system that something is wrong and activating it so that it can help deal with the situation.

By releasing the messenger proteins (called cytokines), injured/sick cells kick off a process that results in multiple types of immune cells entering the troubled area of the body and undertaking very specific tasks.

The inflammatory process. Source: Trainingcor

The strength of the immune response depends on the volume of the signal arising from those released messenger proteins. And there are processes that can amplify the immune response.

One of those processes is called inflammasomes.

What are inflammasomes?

Continue reading “When Inflazome becomes Roche” →

The PASADENA study announcement (part 2)

~ Simon ~ 15 Comments

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In April of this year it was announced that the closely watched Phase II PASADENA clinical trial had not to met its primary objective. This was a large clinical evaluation of an immunotherapy approach (called prasinezumab) for disease modification in Parkinson’s. 

At the time of the announcement, it was indicated that the researchers who conducted the study had seen “signals of efficacy” in the data.

This week the results of the study were presented at an international conference and it was reported that prasinezumab “significantly reduced decline in motor function by 35% (pooled dose levels) vs. placebo after one year of treatment“.

In today’s post, we will discuss what the PASADENA study was, review the results that have been released, and discuss what might happen next.

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At 7am (just prior to the opening of the Swiss Stock Exchange) on Wednesday 22nd April 2020, the pharmaceutical company Roche published its sales results for the 1st Quarter. The financial report looked good, particularly considering the current COVID-19 economic climate, but there was one sentence on page 133 of the results (highlighted below) that grabbed a lot of attention:

From page 133. Source: Roche

For those of you (like myself) who struggle with fine print, the sentence reads:

“Study did not meet its primary objective, but showed signals of efficacy“

This was how the Parkinson’s community found out about the top line result of the closely followed Phase II PASADENA study evaluating the immunotherapy treatment prasinezumab in individuals recently diagnosed with Parkinson’s.

Many within the Parkinson’s community were basically:

Yet another negative clinical trial result.

But then, later that same day, the biotech firm Prothena – which developed prasinezumab and is partnered with Roche in the clinical testing – kindly provided a press release.

And in that document, the company repeated that prasinezumab “showed signals of efficacy” , but importantly: “These signals were observed on multiple prespecified secondary and exploratory clinical endpoints“.

And then the Parkinson’s community was like:

This week we found out more about those “signals of efficacy” and the results of the PASADENA study, and they look interesting.

What do the results show?

Continue reading “The PASADENA study announcement (part 2)” →

The Pasadena study announcement

~ Simon ~ 7 Comments

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This week the outcome of an ongoing Parkinson’s clinical trial was announced.

Data collected during Part 1 of the ongoing Phase 2 PASADENA alpha synuclein immunotherapy study for Parkinson’s apparently suggests that the treatment – called prasinezumab – has not achieved it’s primary endpoint (the pre-determined measure of whether the agent has an effect in slowing Parkinson’s progression – in this case the UPDRS clinical rating scale).

But, intriguingly, the announcement did suggest ‘signals of efficacy‘ in secondary and exploratory measures.

In today’s post, we will discuss what immunotherapy is, what we know about the PASADENA study, and why no one should be over reacting to this announcement.

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At 7am on Wednesday, April 22nd, 2020, the pharmaceutical company Roche published its sales results for the 1st Quarter. This was just prior to the opening of the Swiss Stock Exchange. The financial report looked very good, particularly considering the current COVID-19 economic climate.

There was, however, one sentence on page 133 of the results that grabbed some attention:

Source: Roche

For those of you (like myself) who struggle with fine print, the sentence reads:

“Study did not meet its primary objective, but showed signals of efficacy“

This was how the pharmaceutical giant announced the top line result of the ongoing Phase II PASADENA study evaluating the immunotherapy treatment prasinezumab in recently diagnosed individuals with Parkinson’s (listed on the Clinicaltrials.gov as NCT03100149).

At the time of publishing this SoPD post, Roche are yet to provide any further information (press release, announcement, memo, tweet, etc) regarding the results of the study.

Thankfully, a smaller biotech firm called Prothena – which is also involved in the development of the agent being tested in the Pasadena study – has kindly provided a few more details regarding these results.

I usually don’t like discussing clinical trial results on the SoPD until the final report is published, but in this circumstance I will make an exception.

In today’s post we will discuss what details have been shared in the Prothena press release regarding the Prasinezumab clinical trial in Parkinson’s (Click here to read the press release).

What is Prasinezumab?

Continue reading “The Pasadena study announcement” →

Making sense of antisense

~ Simon ~ 11 Comments

 

Recent regulator approvals and exciting new preclinical data has refocused attention on a treatment approach for genetic conditions that has travelled a long and winding road towards clinical use.

Antisense oligonucleotides represent a method of altering protein levels at the post transcriptional level – it basically stops certain RNAs from being translated into protein.

And recently, a new clinical trial has been registered which will explore the use of this treatment approach in people with Parkinson’s.

In today’s post, we will look at what antisense oligonucleotides are, how they work, what research has been conducted in the context of Parkinson’s, and some of the limitations of this approach that still exist.

 

Source: Youtube

Spinal muscular atrophy (or SMA) is a genetic disorder that results in the degeneration of motor neurons in the spinal cord. This leads to progressive weakening and atrophy of muscules, ultimately leaving sufferers paralysed. It is caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene.

It is a terrible condition that starts in very young children and has an incidence approaching 1:10,000 live births.

Luckily, novel therapies are being developed to deal with this condition, and in 2016, the US FDA approved a new treatment – following rather dramatic clinical trial results – called Nusinersen. This new therapy has caused a great deal of excitement as it basically halted the progression of SMA in many cases.

And a recent long term report highlights some of these very impressive results:

Title: Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies.
Authors: Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, Montes J, Mignon L, Xia S, Bennett CF, Bishop KM, Shefner JM, Green AM, Sun P, Bhan I, Gheuens S, Schneider E, Farwell W, De Vivo DC; ISIS-396443-CS2/ISIS-396443-CS12 Study Groups.
Journal: Neurology. 2019 May 21;92(21):e2492-e2506.
PMID: 31019106                (This report is OPEN ACCESS if you would like to read it)

Most importantly, Nusinersen is having real impact on the children who are affected by this condition:

Interesting, but what exactly is Nusinersen?

It is an antisense oligonucleotide.

What are antisense oligonucleotides?

Continue reading “Making sense of antisense” →

The 2019 ADPD meeting

~ Simon ~ 9 Comments

 

On the 26-31st March, the 14th International Conference on Alzheimer’s and Parkinson’s Diseases (or ADPD meeting) was held in Lisbon, Portugal.

For 5 days – between 8:30am and 7:30pm each day – over 4000 researchers were able to attend lectures of new results and ideas, in any of 8 different auditoriums. Alternatively, they could wander among hundreds of research posters.

It was a marathon effort, however, for all attendees. And a great deal of new results were shared.

In today’s post, we will discussed what was presented at the 2019 ADPD meeting and what was actually learnt.

 

Lisbon. Source: stmed

Lisbon is a city, midway down the western coast of the Iberian Peninsula.

It is home to a little over 500,000 people (3 million in the wider metropolitan area), and it serves as the capital city for the Portuguese people.

The Castelo de Sao Jorge, rises above Lisbon. Source: Wikipedia

Interestingly, it is the 2nd oldest European capital city (after Athens), and has had a rich and fascinating history given its strategic location. But on the 1st November 1755, 20% of the population were killed and 85% of the city’s structures were destroyed by a terrible earthquake and subsequent tsunami, which resulted in the vast majority of the city being rebuilt.

The ‘new city’ is laid out in bairros de Lisboa (neighbourhoods of Lisbon) across a hilly landscape, providing views of the River Tagus at every vantage point. And while walking the steep cobblestoned streets is delightful, there is a system of vintage public trams that can take a lot of the leg work out of the effort.

Source: Portugaltravelguide

During the last week of March 2019, Lisbon was the site of the ADPD meeting.

What is the ADPD meeting?

Continue reading “The 2019 ADPD meeting” →