From Fulcrum Therapeutics press release.
Fulcrum plans to launch a Phase 2b clinical trial in FSHD in mid-2019
CAMBRIDGE, Mass., April 23, 2019 – Fulcrum Therapeutics, a biotechnology company focused on discovering and developing therapies to rebalance gene expression, today announced an exclusive worldwide license agreement with GlaxoSmithKline (GSK) for development and commercialization of the investigational drug losmapimod. Fulcrum intends to advance losmapimod into a Phase 2b trial in the rare and devastating genetic disease facioscapulohumeral muscular dystrophy (FSHD), for which there are currently no approved treatments.
Under the terms of the agreement, as payment for the license, GSK received shares of Fulcrum preferred stock representing a high single-digit ownership percentage of the company on a fully diluted basis, and will be eligible to receive future milestone payments and royalties. Fulcrum obtained all worldwide development and commercialization rights for losmapimod, as well as existing drug substance and drug product materials for use in its clinical trials. Fulcrum also received a right of reference to INDs filed with the FDA relating to losmapimod and an exclusive license to all related patents and data, which build on Fulcrum-generated intellectual property.
“Losmapimod is a foundational clinical asset for Fulcrum that has the potential to become the first approved therapy that targets the root cause of FSHD. Fulcrum believes losmapimod has the potential to slow or halt the progressive muscle weakness that characterizes the condition, which would significantly improve patients’ quality of life,” said Robert J. Gould, Ph.D., Fulcrum’s president and chief executive officer. “The agreement shows confidence in our unique approach to rebalancing gene expression in severe genetically defined disorders. We will work urgently to advance the compound through the clinic.”
Fulcrum’s proprietary product engine identified inhibitors of p38α/β mitogen activated protein kinase (MAPK) as powerful inhibitors of DUX4 expression. DUX4 is the gene that is the root cause of FSHD, a progressive muscle wasting disorder. Losmapimod is a selective p38α/β MAPK inhibitor that GSK has tested extensively in clinical trials, but never in muscular dystrophies. Fulcrum’s novel insight into the DUX4 regulatory pathway led the team to review existing p38α/β MAPK inhibitors, and Fulcrum identified losmapimod as a compound with the potential to address the root cause of FSHD by decreasing DUX4 expression.
GSK evaluated losmapimod in more than 3,500 healthy volunteers and patients in 24 clinical trials across multiple indications, including several Phase 2 trials and a Phase 3 trial in acute coronary syndrome. The data provide evidence that losmapimod is a well-tolerated agent. Fulcrum has conducted preclinical testing of losmapimod in patient-derived cell models and observed precise and potent downregulation of DUX4 expression and restoration of a healthy muscle phenotype without an effect on myogenesis.
Fulcrum has developed an extensive clinical trial network of physicians working on FSHD. An ongoing natural history study of the disease is informing the clinical development plan. Fulcrum expects to initiate a Phase 2b clinical trial of losmapimod in patients with FSHD at multiple clinical sites in the U.S. and Europe in mid-2019.
About FSHD
FSHD, one of the most common muscular dystrophies, is a progressive, degenerative and profoundly disabling disorder estimated to affect about 1 in 8,333 to 1 in 20,000 people globally. There are no approved treatments. Symptoms typically arise in adulthood, often beginning with muscle weakness in the face, leading to an inability to smile. The weakness progresses to the upper body and advances to the lower limbs, leaving many patients unable to lift their arms above shoulder level or to rise from a sitting position. People with FSHD often have difficulty performing daily tasks on their own and may experience severe fatigue and pain. FSHD is caused by a single gene, DUX4, which is normally switched off at the earliest stages of embryonic development. Patients with FSHD have a mutation that causes the gene to remain “on” and to continue producing a protein toxic to muscle tissue.
About Losmapimod
Losmapimod is a selective p38α/β mitogen activated protein kinase (MAPK) inhibitor initially developed by GlaxoSmithKline and in-licensed by Fulcrum Therapeutics. Fulcrum identified the compound as a potent regulator of the expression of the DUX4 gene, which causes FSHD. Losmapimod has been evaluated in more than 3,500 healthy volunteers and patients in 24 clinical trials across multiple indications, including in several Phase 2 trials and a Phase 3 trial. It has been shown to be generally well tolerated.
About Fulcrum Therapeutics
Fulcrum Therapeutics is discovering and developing small molecule therapies to treat genetically defined diseases at their root cause by modulating the expression of the genes known to drive or ameliorate disease. Fulcrum’s proprietary approach to studying disease biology in patient-derived and other relevant human cell lines, coupled with a computational biology engine, generates valuable insights into a wide array of genetically defined diseases. Please visit www.fulcrumtx.com.
CONTACTS
Media: Stephanie Simon
Ten Bridge Communications
stephanie@tenbridgecommunications.com
617-581-9333
Wow! If effective, the re-targeting of this drug cuts many years off delivery to patients.
Please consider a clinical trial in Toronto Canada.
Consideration of a clinical trial in the Houston, Texas area would be appreciated as well!
Moved to tears by the hope this brings!!! Thank you GSK! Thank you Fulcrum! Thank you to everyone who has and will participate in clinical trials! Prayers are being answered!
My husband and son has FSHMD and live in the Washington DC area. Will there be a clinical trial in this area? We are interested in participating in a clinical trial. Thanks
Do monitor clinicaltrials.gov, and also if you are not already a patient at either Kennedy Krieger Institute (Dr. Kathryn Wagner) in Baltimore or Virginia Commonwealth University (Dr. Nicholas Johnson), we recommend it. These are two leading FSHD research centers and would have a high likelihood of becoming future clinical trial sites.
I would be interested in knowing where to closest trial location would be to southern West Virginia. Thanks!
We will be notifying patients once we know the sites where the trial will be conducted. You can also monitor clinicaltrials.gov, and I strongly recommend you enroll as a patient at the FSHD Clinical Trial Research Network site at Virginia Commonwealth University, with Dr. Nicholas Johnson and his team. Try contacting Liz Diaz Email: Liz.Diaz@vcuhealth.org. Phone: 385.988.0742. She is the coordinator of the Fulcrum biomarker study going on there now. This is not the drug study but is a very important preparatory study to help Fulcrum design their trial.
Great news!
I am a father of 3 daughters, 2 of them with Fshd. I desire to know better clinical trials and evolution of this discovery.
I need to know where are trials in Europe or in Italy where I live.
Thank you so much for your work.
The clinical trial sites for Fulcrum have not been announced yet. We recommend you check clinicaltrials.gov regularly. All clinical trials have to be listed in that database and will include a list of where the trial is being done. In addition, we recommend that your daughters enroll as patients and research volunteers at the FSHD Clinical Trial Research Network collaborating site in Italy, at the University of Milan. Valeria Sansone, MD, is the principal investigator there.
Terrific news! People with this disease, including me, will be thrilled to learn of trials in their area. I live in the Denver CO metro area and would like to follow-up with the clinicaltrials.gov site.
Blessings and Prayers,
Jeff
Dear June,
are you in contact with Dr Dubrovsky of Fundacion Favaloro ? Buenos Aires, Argentina, they investigate Neuromuscular Dystrophy.
Best wishes.
Thank you, thank you, thank you all! From the bottom of my heart I am so grateful for EVERYTHING and EVERYONE that went into this project! Four of my family members (including myself) struggle with this disease. This will be such a blessing. If any clinical trials develop in CO I would love to be a part of it.
My son lives in Gilbert Arizona. Will there be clinical trials there.
I’m always skeptical regarding clinical trials led by private firms. I remeber how aTyr trials were abandoned, were they not ?
Agreed. Especially, trials led by one private firm, that has global rights for the potential therapy.
If I understand this correctly, even if there were other teams working on a cure and they come up with a solution, they cannot publish it, because it would violate Fulcrum’s global rights…
Doesn’t it discourage other teams to work on this?
“An ongoing natural history study of the disease is informing the clinical development plan.”
What does this entail? Do we know how long FSHD has been present in humans? Is that something this history study address?
My husband just received results of his test today. We have 3 sons so of course there is some shell shock and worry. This gives us hope!! Definitely interested in participating in clinical trials.
Hi!
This sounds great, and I really wish it will work. Any chance a patient from Israel could enroll to one of these trials?
As hopeful as I am, phrase “acquires global rights” makes me worried.
I am living with FSHD and there is very little in my life that I would want more than to have a cure available.
However, having a single company acquiring global rights to this treatment makes me remember story of the infamous Martin Shkreli, aka Pharma Bro. TLDR: Martin was involved in buying medical companies that had global rights to certain drugs and marking up those drugs several hundred, if not thousand, percent. He is currently incarcerated. If you’re interested, listen to season 5 of “Legal wars” podcast.
What I am trying to say is that this exclusivity discourages other teams from working on solution. At the end of the day, who would work on something that they cannot make public because someone else has global rights to…
This sounds so wonderful !
I am dealing with FSH and this gives Hope !
Please let me know of any clinical trials in the Pennsylvania , Ohio area !
Thank you all so much for all the hard work in helping those of us who have this disease. It’s running it’s toll on my family. Started with my father whom lived to 80, spread to myself and two brothers. Now I see it passed to my three of my nephews. Is there a place in Indiana where we can go for these trials? Thank you
Is it likely that the clincal trial sites will be the same as those that are conducting the current natural history study, such as in Kansas City and Salt Lake City? Will those involved in the natural history study be likely candidates for the clinical trials?
Will there be clinical trials in Pittsburgh or close by?
How about clinical trials in Long Island, NY?
I am in the Los Angeles area. Hopefully, that area will be part of the clinical trial.
Will there be a list that comes out publicly of where these trials will take place. I am in the Chicago area and would love to be a part of the trial.
We will be contacting individuals in the vicinity of a trial site as the sites begin to enroll volunteers. So please make sure we have your current address and email.
I am from Hyderabad, India. Is there any clinical trials in India or near by country’s, please inform me.
At this time there are no trials being planned for India. We encourage individuals everywhere to do what they can to maintain their health through a good diet, exercise, and healthy attitude, while supporting our efforts to accelerate the development of treatments.
Seitdem ich erfahren habe, dass meine erheblichen körperlichen Behinderungen ihre Ursache in einer FSHD 1 Erkrankung haben, greife ich nach jedem “Strohhalm” in Form von Pulvern, Tableten, Infiusionen und Physotherapeutischen Behandlungen um meine Lebensqualität zu verbessern. Ich lese daher mit großem Intersse und Hoffnung von diesem neuen Medikament, dass ich in einer Studie sehr gerne ausprobieren würde….Bitte informieren Sie mich, ob und wo ich in Deutschland an einer Studie teilnehmen kann…
Hola, una noticia tan importante y esperanzadora, necesito saber si tienen contacto para la experimentación con el Dr. Dubrosky de la Fundación Favaloro o Dr Ruggiero del Hospital Italiano de
Buenos Aires, Argentina. Yo estoy atendiéndome con ellos y quisiera participar.
Donde me aconsejan dirigirme.
Muchas gracias.