LRRK2 Drug Trial Shares Promising Results,
Company to Begin Second Study
Posted by Maggie McGuire Kuhl,
December 21, 2017
Yesterday Denali Therapeutics announced positive results from its first-in-human LRRK2 inhibitor clinical trial. The experimental treatment is safe, and it lowers LRRK2 protein activity in humans' body cells. This is a meaningful milestone in the clinical development of a drug with potential to slow or stop Parkinson's progression (something no currently available treatment can do).
Denali also shared it is testing a second compound in a separate Phase I trial in control volunteers. Following completion of both trials, one of the two compounds will move into studies in people with Parkinson's carrying a LRRK2 mutation.
Read more below on this project and its treatment potential from our earlier report on Denali's initial public offering.
In a press release, the company announced its first trial showed greater than 90 percent inhibition of LRRK2 activity at peak drug levels. This is a critical early step in testing a drug -- does it do what you want it to do in the cell? Denali used two tests to measure inhibition, including one based on a finding from a Michael J. Fox Foundation-organized consortium linking LRRK2 to another protein.
"Mutations in LRRK2 are a major risk factor for Parkinson's disease. Targeting this degenogene represents a promising approach to develop disease-modifying medicines," said Ryan Watts, PhD, Denali CEO.
Read more on the findings and next steps.
December 8, 2017 -- San Francisco-based Denali Therapeutics has raised nearly $250 million in its initial public offering, marking the largest biotech IPO of the year. In announcing terms of the IPO -- a major milestone in the life cycle of any company as it first offers stock options publicly, garnering capital for growth and expansion -- Denali shared it is testing a LRRK2 inhibitor drug in a small trial of control volunteers.
Mutations in the LRRK2 gene are a cause of Parkinson's disease (accounting for one to two percent of all cases, but behind up to 40 percent in some populations) and are associated with higher activity of the LRRK2 protein. Scientists, therefore, are developing inhibitor drugs to offset that over-activation and protect cells. The Michael J. Fox Foundation has a robust roadmap strategy around LRRK2: funding many studies to understand more about the protein's connection to Parkinson's and how we may target it to slow or stop disease.
While we have not directly funded Denali, our investments have been critical to helping the company achieve its current promising LRRK2 program. Denali has used MJFF-supported research tools in its experiments, and an August 2016 Forbesarticle reported CEO Ryan Watts cited a unique MJFF-led consortium as influential in his decision to license and develop LRRK2 inhibitor compounds. The LRRK2 Safety Initiative tested compounds from Genentech, Merck and Pfizer for safety, finding lung tissue changes were reversible and not associated with functional problems.
"This is a textbook example of what we exist to do: persevere to overcome issues that would otherwise set PD drug development back by years," MJFF CEO Todd Sherer, PhD, told Forbes. "We're thrilled on behalf of everyone living with the disease that a highly-promising target continues to move forward."
Therapies like this -- targeting dysfunction associated with a genetic mutation -- are examples of precision medicine, prescribing treatments based on one's biology rather than clinical diagnosis. Earlier this year another Parkinson's trial began enrolling people with a mutation in the GBA1 gene, also associated with the disease.
A common question is if such therapies will work for people without those specific mutations. While we do not yet know, our Foundation is funding research to draw lines between implicated proteins and pathways, which may lead to wider use of treatments.
As its first human study continues, Denali gained approval to begin a trial of a different LRRK2 inhibitor compound in the Netherlands and also is developing therapies against Alzheimer's disease and amyotrophic lateral sclerosis (ALS). We will share more news on the company's Parkinson's trials as it is available.
Good morning, friends! I woke up to the most amazing surprise in my email; it shocked me straight awake. It was from the founder of Feedspot.com, the RSS Feed for bloggers. informing me that my blog has been named one of the TOP 50 PARKINSONS BLOGS on the web today. Click here to see their full story: http://blog.feedspot.com/parkinson_blogs/
The founder, Anuj Agarwal wrote: "I personally give you a high-five and want to thank you for your contribution to this world. This is the most comprehensive list of Top 50 Parkinson Blogs on the internet and I’m honored to have you as part of this!" To say this is a shock is way understating how I feel at the moment.
Their RSS Feed is subscribed by all of the major news organizations (TV, radio, print). If you don't know what an RSS Feed is - you can subscribe to many different publications and Feedpost will send you an email each morning with headlines so you can read what you are interested in vs. having to read every single website individually. Feedsport.com is offering my blog as one of the 50 choices for Parkinson's information available. Please check it out. Go to FEEDSPOT.COM, open an account for yourself and subscribe to my blog along with other amazing outlets, including the Michael J. Fox Foundation, the National Parkinsons Foundation, Parkinsons News Today and the Brian Grant Foundation! I am in their amazing company.
I know I need to breathe, but am having a bit of a hard time doing that. Isn't it funny and incredibly humbling when your life changes in a nanosecond? Synchronicity still thinks I have a way to go before I am perfectly in balance so I give up my control and let the Universe keep re-arranging. Friends, we are on the ride of our lives.
Thank you to Anuj and his crew for this honor. Thank you God for my life every single day. I have a beautiful life I would not trade for anything with beautiful loves and angels surrounding me at all times. Amen.
It was bound to happen. Cynapsus Therapeutics announced today that it is being bought out by Sunovion Pharmaceuticals for $40.50 per share. This morning Cynapsus woke up to $18.36 per share and celebrated the end of that day at $39.70. UP $21.34. Very well deserved. Let's get this drug I am on out to the masses.
I feel so incredibly blessed to be only 1 of 106 on this last leg of the trial. And, of course, I have a story to share from last night. My husband, Lee and I took in an AC/DC concert here in Fort Lauderdale with friends. The concert (with Axl Rose in for Bon Scott doing an A-M-A-Z-I-N-G job, by the way) was soooo much fun. Until three-quarters of the way in. That's when for some bizarre reason, the pounding from the instruments through the speakers made a change in my body and wore my Carb-Levo off in an instant (no kidding). There was no "wear off". It was one minute on and the next off in full tremor. Normally I would have made a beeline for the bathroom and cried out the rest of the concert. It was took early to take more Sinimet so I would have been rocking and rolling (no pun intended, trust me) for another 2 hours until the next dose. Instead I popped a sublingual APL-130277 under my tongue and within 10-15 minutes I was completely still like it never happened. I am still dumbfounded that this miracle drug has entered my life and taken PD on and shut it down.
To everyone around me it looked like I was dancing. To me, my heart was palpitating as I realized I was have a PD attack in a crowd of thousands. Speechless. That's what I am. Grateful beyond words. And humbled by the work of hundreds of researchers who are doing this for me.... and for you.
Thank you Cynapsus. And as always, a very special THANK YOU to the Michael J. Fox Foundation, who without I would be incapacitated at 52 years old. Instead I am very alive, very vibrant, very active, very viable and still enjoying the fruits of a (somewhat) normal life.
2,786 days walking with Parkinsons and counting.
7 years, 7 months, and 17 days.
Ironically that it adds up to the number 22, which is my birthdate and my lucky number
More importantly, it is "MASTER NUMBER" in Kabbalah numerology.
One of the most revered numbers.
The month of August which started my personal cycle to start to skyrocket started out on August 1, 2016 adding up to CHAI. The number 8. Ana, you are right - as usual. You can't get any better than that.
Today is a very good day.
Today I woke up another year older and a whole lot less shaky!
Today I began my participation in the Phase 3 Safety Trial for APL-130277 and I received a birthday present that blows the imagination. You have to watch this!!!!
P.S.: You have my permission to share this video, especially if you know anyone with PD.
Reposted from the FoxFeed Blog
Under-the-Tongue Film Strip for "Off" Rescue Moves Closer to Market
Posted by Maggie McGuire Kuhl,
August 16, 2016
Clinical trial news update: Cynapsus Therapeutics Inc. recently announcedresults from the Phase II trial of their listerine-like strip "off" rescue therapy to restore motor function when the effects of levodopa begin to drop. The therapy is now in Phase III testing, and Cynapsus anticipates filing for a new drug application (a formal proposal from the company to the FDA asking for drug approval) in the first half of 2017; the FDA must review all safety and efficacy data in the application before it decides on approval, which can take up to 10 months.
MJFF promoted recruitment of these trials through Fox Trial Finder and is funding a sub-study within the Phase III trial, in which data will be collected from a subset of participants through the use of wearable devices and MJFF's Fox Insight smartphone application (developed in partnership with Intel). Read more below about this therapy and MJFF's support of its development:
The development of a user-friendly "off" rescue therapy recently reached two monumental milestones that will propel it closer to pharmacy shelves.
Cynapsus Therapeutics Inc. is testing a thin-film, under-the-tongue strip (similar to those offered by Listerine for fresh breath) to quickly restore motor function when the effects of levodopa wane. ThePhase I study — funded by The Michael J. Fox Foundation — reported positive results, and the company secured $25 million from investors to support further development.
The thin-film strip is a reformulation of an available drug, apomorphine, that is injected for rescue from "off" episodes. People with Parkinson's disease can go from "on" to "off" when the concentration of levodopa (the primary PD drug) in the bloodstream drops, causing a reemergence of motor symptoms. As patients take levodopa over the long-term, the drug can wear off before the next allotted dosage. Taking more levodopa upon "off" is undesirable since too much of the drug can cause debilitating side effects.
Apomorphine is the only available drug for "off" rescue, but the need for injection discourages use. It also may cause side effects of nausea and vomiting. The under-the-tongue formulation, called APL-130277, may be easier to use and offer longer relief than the injected apomorphine. Initial studies show fewer side effects, as well.
The Phase I study in control volunteers tested how much of the drug from the strip reached the bloodstream and how fast it did so, compared to the established already available injectable. Cynapsus found similar results: the 10mg strip correlates to the profile of the 2mg injection, and the 15mg strip to the 3mg.
Since this study was in control volunteers, they do not know for certain how fast the strip can relieve motor symptoms. However, they do know the level of the drug in the blood that is usually the "on/off" threshold. The strip took 10 minutes to reach that threshold, compared to about six minutes with the injection.
Accounting for the time to fill a syringe and self-inject versus place a strip under the tongue, though, may offset that difference. Furthermore, the effects of the strip on motor symptoms may last longer than the apomorphine from injection.
"Patients can defer taking another dose of levodopa perhaps even longer than they would have scheduled, and we know fewer levodopa is a good thing in the long run," said Albert Agro, PhD, chief medical officer at Cynapsus.
A separate study from Cynapsus of a 25mg dose of APL-130277 showed faster time to reach the "on/off" threshold and longer efficacy.
Their next step is to test these doses in people with Parkinson's. The study is still being planned. When sites start recruiting, the details will be listed on Fox Trial Finder.
The $25 million follow-on investment for this study is a testament to the MJFF de-risking model, supporting early-stage research to make these projects more attractive to larger funders.
"We look forward to initiating the efficacy program in patients suffering from Parkinson's disease with debilitating motor complications," Dr. Agro said.
Said Anthony Giovinazzo, CEO of Cynapsus, "Our partnership with The Michael J. Fox Foundation is very important to us as not only does it provide credibility, but they have the means to help us accelerate our recruitment."
Register with Fox Trial Finder today to be matched with clinical studies recruiting in your area.
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