The Phase 1/2 CDNF topline results

 

 

Neurotrophic factors are naturally occuring proteins that help to keep neurons alive, provide a supportive environment, and encourage growth. For a long time, researchers have been exploring methods of utilising the power of neurotrophic factors in regenerative strategies for neurodegenerative conditions, like Parkinson’s. Today, the biotech firm Herantis Pharma announced topline results of their Phase 1/2 clinical trial of the neurotrophic factor Cerebral Dopamine Neurotrophic Factor (or CDNF). In today’s short post, we discuss what CDNF is, explore what the trial involved, and consider what the

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Source: Herantis

It is cold this time of year in Helsinki, but there will be some warm smiles there today.

A small biotech firm called Herantis Pharma has announced the topline results of their Phase 1/2 clinical trial exploring the safety and tolerability of a treatment called CDNF.

What is CDNF?

CDNF (or Cerebral Dopamine Neurotrophic Factor) is a naturally occuring neurotrophic factor.

What is a neurotrophic factor?

Neurotrophic factors (neurotrophic (Greek) = neuron – nerve; trophikós – pertaining to food/to feed) are chemicals that nurture neurons and support growth. Think of them as fertilizer for cells.

There are many types of neurotrophic factors, some having more beneficial effects on certain types of neurons and not other. GDNF (or glial cell line-derived neurotrophic factor) which has recently been tested in Parkinson’s is another example of a neurotrophic factors (Click here to read a recent SoPD post on this topic).

Herantis Pharma has kindly produced this video explaining CDNF:

For readers seeking a bit more detail as to how CDNF works, I can recommend this recent review article from researchers involved with Herantis:

Title: CDNF Protein Therapy in Parkinson’s Disease.
Authors: Huttunen HJ, Saarma M.
Journal: Cell Transplant. [Epub ahead of print]
PMID: 30947516               (This report is OPEN ACCESS if you would like to read it)

In this review, the researchers provide a very thorough explanation of how CDNF has its beneficial effect (specifically, it reduces endoplasmic reticulum (ER) stress):

The actions of CDNF. Source: Sage

The review also provide a timely overview of the previous clinical trials of neurotrophic factors in Parkinson’s.

Interesting. So what did the CDNF clinical trial involve?

Over the last 2 years, Herantis has been conducting a Phase 1/2 clinical trial of CDNF in 17 people with advanced Parkinson’s.

CDNF does not cross the blood brain barrier – the protective membrane surrounding the brain – so the researchers have employed a sophisticated delivery system. They used the same delivery system that was used in the Parkinson’s UK/Cure Parkinson’s supported Phase 2 Bristol GDNF clinical trial (Click here to read a recent SoPD post about this).

This device involves tubes being implanted deep into the brain with pin point precision thanks to the assistance of robotics (a system developed by Prof Steven Gill and a company called Renishaw). These tubes connect with another tube which runs to a small port that is placed just behind the ear.

The CDNF delivery system. Source: Medium

CDNF could be pumped into the brain via the small port place behind the ear once a month.

In the CDNF clinical trial, one-third of the participants received monthly infusions of a placebo solution while the remaining participants received monthly infusions of either mid- or high-doses of CDNF for a period of 6 months. The participants were randomly assigned to these grouping (Click here to read more about the trial).

The study is now in a follow up extension arm which involves another 6 months of treatment, but during this period all of the participants will receive monthly infusions of either mid- or high-dose of CDNF (Click here to read more about this follow up study).

And when this extension finishes for each participant, they will be invited to take part in a longer-term (4 year follow up study – click here to read more about this study).

So what were the results?

At present there has just been a press release, so the details are few (Click here to read the press release). We really need to wait for the publication of the full results.

But what Herantis has shared is encouraging.

Safety/tolerability was the primary interest of the investigators during this first part of the study and the treatment appears to have been safe (“The recorded Serious Adverse Events (SAEs) were considered unlikely by the treating physicians to be related to CDNF and the affected patients fully recovered“).

There were also a range of exploratory endpoints employed in the study. These were used to see if any initial signs of efficacy could be determined. They included clinical assessments such as the Unified Parkinson’s Disease Rating Scale (UPDRS), brain imaging methods (such as dopamine transporter PET scan), and biological measures (such as alpha-synuclein protein levels in bodily fluid samples).

While the study is small (only 17 participants) and not designed to evaluate efficacy, Herantis wrote this is the press release regarding the secondary endpoints:

“At this early stage of data review, the Company observed promising signals in some patients, for instance in dopamine transporter PET imaging, which is an indirect measure of the dopaminergic function. As the trial is a first-in-human study involving a small number of patients at an advanced disease stage, this is an encouraging initial outcome. The Company will continue to assess the results through the extension part of the study which will last six months”

Herantis expects to be able to announce the results of the next part of the clinical trial (the 6 month extension) in the autumn of this year, and those results will apparently include some of the exploratory endpoints. Expect another SoPD post on this topic when they become available.

Interesting. So summing up?

Not yet. There were two other details mentioned in the press release worthy of mentioning.

First, Herantis announced that they “have initiated the planning for a Phase 2 study with a longer treatment period that will assess the efficacy of CDNF in earlier-stage, well-characterized Parkinson’s patients. We currently expect to initiate patient enrolment in 2021“.

So the company is evidently happy enough with what they are seeing to press ahead and invest in further development of this approach.

And that is probably the most positive take away from this press release.

Second, Herantis will be holding a webcast to discuss the results in a few days time (on Friday 28th February 2020 at 10:00 AM CET). They will be taking questions, but only if submitted prior to the start of the webcast (questions can be emailed to webcast@herantis.com). And to participate, you need to register beforehand for the “CDNF webinar Feb 2020” on this website.

So what does it all mean?

Here at the SoPD we have been awaiting the results of the CDNF. Admittedly, they took me completely by surprise today as I was not expecting to see them until the completion of the extension arm of the study later in the year. But they were a welcomed surprise, as this early annoucement suggests the company feels positive about the treatment.

It has to be said that the treatment involves a rather invasive procedure (with the implanting of tubes in the brain). But there are efforts being made by research groups to develop alternative versions of CDNF and different methods of delivery (for example, there is preclinical data for a gene therapy approach – click here to read more about this).

So while these ongoing clinical studies may provide proof-of-principle (and the participants should be knighted for their incredible bravery), it will be further encouraging to see some less invasive methods coming forward for clinical evaluation as the field of neurotrophic factors for Parkinson’s progresses.

Watch this space, I guess.

 

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EDITOR’S NOTE  – The author of this post is an employee of the Cure Parkinson’s Trust and the President of his local Parkinson’s UK support branch. Both of these organisations – the Cure Parkinson’s Trust and Parkinson’s UK – funded the Bristol Phase II clinical trial of GDNF in Parkinson’s. Neither organisation nor the GDNF team at Bristol Hosptial have asked for this post to be written. This post has been provided by the author solely for the purpose of sharing what he considers to be an interesting story of medical research.

Herantis Pharma is a publicly traded company. That said, the material presented on this page should under no circumstances be considered financial advice. Any actions taken by the reader based on reading this material is the sole responsibility of the reader. Herantis Pharma have not requested that this material be produced. This post has been produced solely for educational purposes.

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The banner for today’s post was sourced from Herantis.