At the world fights a global pandemic some encouraging news for the multiple system atrophy community is very welcome. Though we must still await the results of the Verdiperstat phase 3 clinical trial (currently underway), should the results be positive the FDA decision to fast track Verdiperstat could pave the way for a faster approval of the drug. We are grateful to Biohaven and the FDA! #MSACoalition #BuildingHopeforMSA
We know the MSA community have many questions about Verdiperstat. See below for the latest updates directly from the drug company Biohaven Pharmaceuticals.
*** UPDATE (as of June 11, 2021)
Q. Can I still join the trial?
A. Enrollment for the phase 3 study closed in July of 2020
Q. When are we expected to know the results of the Phase 3 study?
A. Biohaven’s expectation is that Top-Line results will be available by the end of the third quarter in 2021.
Q. If the results are positive, what happens next?
A. If the Phase 3 study results are positive and show that verdiperstat is effective, then Biohaven will engage with the FDA to discuss next steps.
Q. Is there anything we can do as patients or caregivers to help?
A. Continued advocacy work to raise awareness about MSA, including diagnosis and treatment gaps, as well as the burden of the disease on patients and families.
Q. What is the plan for patients who live outside the United States?
A. If the Phase 3 study results show a statistically significant effect of slowing disease progression with verdiperstat, Biohaven will engage with the health authorities in Europe and other countries to discuss next steps.
Q. How does the drug work?
A. Verdiperstat is believed to inhibit an enzyme called myeloperoxidase that catalyzes the production of cytotoxic compounds. Buildup of these reactive compounds leads to brain tissue damage and neuronal death. Verdiperstat binds to myeloperoxidase and is believed to reduce the production of reactive compounds and protect nerve cells from damage. Learn more in this video: https://vimeo.com/542176986
Q. Could you tell us anything about how many people have been in the Phase 3 study and where they are from? In the United States or outside of the United States?
A. There are 336 people in the blinded phase 3 trial; half are on placebo and half are on verdiperstat. 35% of patients are in the E.U. (Austria, France, Germany, Italy and UK) and 65% are in the United States.
Q. If people who are taking verdiperstat have questions or concerns, who should they contact?
A. They should contact their study physician.
*** UPDATE (as of November 6, 2020):
The MSA Coalition have received many questions about accessing the investigational drug Verdiperstat. Biohaven Pharmaceuticals have provided some answers:
Q. I live outside of the USA. Can I request expanded access or compassionate use to get Verdiperstat in my country?
Q. Can I still enroll in the clinical trial?
A. No, the trial is now closed to new participants at all study sites globally.
Q. When will the study be completed?
A. It is expected that all currently enrolled patients will have finished this blinded study by July of 2021.
Q. When will the study results be available?
A. No results will be available until after every enrolled patient has completed the trial. Topline results are expected by late 2021.
Q. What is Expanded Access?
A. Expanded Access, also known as “Compassionate Use”, is a pathway through which patients with serious diseases may be able to obtain access to an investigational drug or other therapy outside of a clinical trial.
A qualified physician would need to request access to the drug from the drug company on behalf of a patient. The drug company may agree to allow access if certain conditions are met. In the US the Food and Drug Administration (FDA) oversees this program.
You can learn more about the program at the FDA website.
https://www.biohavenpharma.com/science-pipeline/resources/early-access-programs
—–
*** UPDATE (as of April 9, 2020): We have reached out to Biohaven for clarification about how they are addressing concerns regarding administering the trial during the global pandemic. Their answers are included below.
Q. What does fast track designation mean? Is the drug available now by prescription from my doctor?
A. Fast track designation does NOT mean that the drug is already approved for use to treat MSA. Fast track designation means that the FDA has promised to expedite the review process once the drug company has results to show them from the phase 3 trial. Both the drug company and the FDA will want to examine the results of the phase 3 trial very carefully before there is any decision made on whether to make this drug available to patients. The FDA cannot promise to approve it without first examining the trial results.
Q. What is the timeline for approval? Does this mean the drug could be approved within months or years (if phase 3 works)?
A. If the phase 3 trial is positive we can’t know for sure how long the next steps in the process of FDA approval will take. The phase 3 trial is estimated to complete October 20, 2021.
Q. Why does it take so long to get a drug approved?
A. We understand the timeline is frustrating however there are strict FDA protocols that must be followed. Drugs that are meant to slow disease progression have to be evaluated over the course of time (for a year in the case of MSA). This makes these research studies longer to complete. It takes considerable time to ramp up a study of this size and to find qualified patients to participate. There were over 50 clinical centers that had to be mobilized to recruit and enroll the 250 patients needed. This high number of patients is needed in order to show statistical significance in the results. Patients enrolled must each be on the drug or placebo for one year will need to be monitored closely at regular intervals.
Q. In light of the Covid-19 pandemic, how is the phase 3 study now being handled? Are different sites handling things differently, or is there a directive from Biohaven on what will happen?
A. Our top priority is to ensure the health, safety, and well-being of our study participants and site staff. As such, we have offered general principles and guidance to M-STAR study sites in response to the COVID-19 pandemic. As there are many people who depend on the work we do, Biohaven will support sites’ efforts to ensure that participants can safely continue in the study and receive their study medication. We encourage sites to follow institutional policies and procedures regarding conducting in- person study visits. We have asked sites to please communicate any potential issues to us as soon as they are aware of them, and we will work with them on a case-by-case basis to address such issues. Biohaven has implemented workaround measures that we believe are in compliance with guidance from health authorities, including the US Food and Drug Administration and European Medicines Agency. Biohaven has provided guidance to sites regarding alternatives, focusing largely on safety measures. We have asked sites that cannot see patients in person in their clinics due to the COVID-19 pandemic to perform remote visits via phone or telemedicine video, collect safety laboratories at local labs, etc. The Institutional Review Boards (IRBs) for the M- STAR study sites have been informed about these potential modifications to the study conduct.
Q. Each study visit involves two blood draws, several hours apart. Is Biohaven expecting people to go to local labs two times in one day for blood draws? If so, this puts people at risk during the global pandemic.
A. During the COVID-19 Pandemic, Biohaven is following the Health Authority guidelines. If patients are unable to go into sites for visits, a remote visit may occur (while the specific details of the patient’s safety are taken into consideration) and blood samples may be collected and analyzed at a local laboratory (such as Quest). These blood draws will be limited to assessing safety laboratories in order to ensure that the participant is tolerating the study drug without negative effects on major organ systems. The two blood draws—one before and one after the dose of study medication—that you are specifically asking about are intended to assess drug levels in the blood. These measurements will not be conducted when blood is drawn at local laboratories during the COVID-19 pandemic. Thus, there will only need to be 1 blood draw at a local laboratory per remote visit.
Q. Will the principal investigators be doing neurological exams virtually? (Each visit involves rating scales, and this could realistically be done virtually.)
A. Remote study visits may be conducted by the site via phone or telemedicine video. Assessments performed during these remote visits will focus largely on ensuring safety of the study participant. If deemed appropriate by the investigator, some aspects of the neurological exam may be performed via telemedicine video. However, we do not
anticipate requiring completion of all the study rating scales via telemedicine video. We are mindful that some participants may not have the same technology resources available. Moreover, the validity and reliability of performing all of these assessments remotely is not ensured.
Q. Will the people currently enrolled stay in the study longer than expected as they won’t be able to have visits with their doctors? (This relates to the validity of the study).
A. Currently, we are focused on ensuring the safety of trial participants and site staff. We believe that the workaround measures that we have implemented (such as remote visits) are in compliance with guidance from health authorities including the US Food and Drug Administration and should not impact the validity of the study. We do not anticipate that participants will remain in the study longer than anticipated, however extended windows to allow flexibility for conduct of visits may be allowed.
Q. Does participating in a clinical trial affect the care someone would receive if sick with Covid 19? If a hospital had to make a choice between who gets a ventilator, can it be assumed that the person in a clinical trial (or with a fatal neurodegenerative disease) would not be selected?
A. Every hospital likely has its own policies regarding the medical care that someone would receive if they develop COVID-19. We do not believe that a patient’s medical care would be affected based on clinical trial participation.
Q. How many slots are still available, and will people have to wait until the quarantine is lifted to try to participate in the trial?
A. Evolving governmental and institutional restrictions implemented due to safety concerns related to the COVID-19 pandemic have limited screening and enrollment of new participants at most, if not all, M-STAR study sites. Once these restrictions are lifted, screening and enrollment will resume. We estimate that approximately half of the target number participants have been enrolled in the study. This study has not officially been put on hold but, due to the restrictions of the institutions involved, the rate of study enrollment has decreased.
Q. As of April 2020, the Verdiperstat Biohaven trial is underway in the USA but has not yet started in Europe. In light of Covid 19 is the trial still planned to take place in Europe?
A. Unfortunately, the M-STAR trial has been significantly impacted due to the unprecedented COVID-19 pandemic. M-STAR study has a planned 250 randomized participants, among all countries enrolling in the M-STAR study. We estimate that approximately half of the target number of participants have been enrolled in the study. This study has not officially been put on hold but, due to the government and institution COVID-related restrictions, the rate of study enrollment has decreased. At this point it is difficult to determine when the global study enrollment limits will be reached. The Europe sites continue to prepare for launch of the M-STAR study once it is safe and feasible to resume clinical activity and currently there are sites open to enrollment in France, Austria and the UK. Biohaven continues to work behind the scenes with study centers in the US and the EU in the hope of moving forward expeditiously with the study as soon as possible, once the safety of trial participants is ensured.
More Information About Verdiperstat:
More information on the Verdiperstat phase 3 clinical trial can be found here: https://clinicaltrials.gov/ct2/show/NCT03952806
More information on the FDA’s drug approval process can be found here: https://www.fda.gov/drugs/development-approval-process-drugs.
More information on fast track approvals can be found here:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track
Verdiperstat video:
https://vimeo.com/542176986
Biohaven Pharmaceuticals expanded access policy:
https://www.biohavenpharma.com/science-pipeline/resources/early-access-programs
Is a clinical trial in Canada possible?
Hi Karen, The trial is running at about 60 sites in the US and Europe. There are no trial sites in Canada currently. You can read about the trial here:
https://clinicaltrials.gov/ct2/show/NCT03952806
We are compiling a list of questions to send to Biohaven. I will be sure to include your question about whether a patient in Canada might have a means to participate. If you have more questions please send them along to me. Feel free to email me for a faster response: pbower@msacoalition.org
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My wife cannot meet the trial criteria at this point in her disease. Can she get a prescription for Verdiperstat with her doctors approval under the right to try law, prior to phase 3 ,FDA approval.
She cannot wait another year!!!!
Hi William,
You will need to involve her doctor who would then get in touch with the drug company.
There is more information here:
https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try
Good luck,
Pam
Hi,
Is this trial also available in Israel? And if so are they recruiting.
Thank
Hi Reut,
The trial is running at about 60 sites in the US and Europe. There are no trial sites in Israel currently. You can read about the trial here:
https://clinicaltrials.gov/ct2/show/NCT03952806
If you have more questions please send them along to me as we are compiling a list of questions to send to Biohaven.
Feel free to email me for a faster response: pbower@msacoalition.org
Hi Pam, I spoke with Doc Kellerman yesterday & he said to get in touch with Biohaven as he thinks because of the Covid 19 they may still be enrolling patients in the Verdiperstat trial. I would definitely like to explore my being in the program. Anything you could do would be greatly appreciated. Thank you
Hi Dennis,
The complete trial information is at this site: https://clinicaltrials.gov/ct2/show/NCT03952806
If I recall correctly you are in California. There are 4 study centers enrolling.
United States, California
UC San Diego Department of Neurosciences Recruiting
La Jolla, California, United States, 92037
Contact: Rachel Schade 858-246-2533 rschade@ucsd.edu
UCLA Medical Center / Neurological Services Recruiting
Los Angeles, California, United States, 90095
Contact: Natalie Skigen 310-206-8153 NSkigen@mednet.ucla.edu
Stanford University Recruiting
Palo Alto, California, United States, 84127
Contact: Ruba Shaik 650-546-1436 rubas@stanford.edu
UCSF Memory and Aging Center Recruiting
San Francisco, California, United States, 95158
Contact: Julia Glueck 415-502-7640 Julia.Glueck@ucsf.edu
Paziente
Hola! Somos de Argentina. Mi esposo tiene MSA tipo C diagnosticado a fines de 2018. El aun camina solo, pero con riesgo de caidas. Si bien tenia criterio para acceder al ensayo clinico, no puede hacerlo porque no vivimos.ni en EEUU ni en Europa. El uso compasivo, es solo para pacientes que viven en EEUU.
Mi consulta es.. que posibilidades hay de acceder a al uso compasibo de Verdiperstat para todos aquellos que no vivimos en EEUU y que tampoco podemos acceder al ensayo clinico por no vivir en el sitio?
En esta situacion estamos todos los que vivimos en America Latina, Oceania, Asia etc. La preocupacion es que para nuestros seres queridos que padecen la enfermedad, esperar a fines de 2021 es mucho tiempo. Hay posibilidad de acceder antes?
Dear Flavia,
Lo siento, la compañía farmacéutica ha declarado muy claramente que no ofrecen acceso compasivo fuera de los EE. UU. Todavía no sabemos si este medicamento será útil, por lo que debemos esperar hasta que se hayan analizado los resultados.
I’m sorry, the drug company has stated very clearly that they do not offer compassionate access outside of the USA. We do not yet know if this drug will be helpful so we must wait until the results have been analyzed.
Best regards,
Pam
I read your Q & A with great interest. It is unfotunet I coud not find anyinfo regading movement dsoder. I wuold to know if this med.will impove my balance or not.
Dear Lale
We are compiling a list of questions to send to Biohaven. I will be sure to include your question about whether it might help balance. If you have more questions please send them along to me. Feel free to email me for a faster response: pbower@msacoalition.org
Is there an M-star study site in Israel? Alternatively is there a way to participate in the study for a patient living in Israel?
Hi Deborah,
The trial is running at about 60 sites in the US and Europe. There are no trial sites in Israel currently. You can read about the trial here:
https://clinicaltrials.gov/ct2/show/NCT03952806
We are compiling a list of questions to send to Biohaven. I will be sure to include your question about whether a patient in Israel might have a means to participate. If you have more questions please send them along to me. Feel free to email me for a faster response: pbower@msacoalition.org
My mother didn’t qualify even though the hospital and doctor at Rush Hospital in Chicago are involved in the trial. My mother is wheelchair bound hence didn’t qualify.
I still have simple questions that even Biohaven website or googling can’t answer, if anyone knows please answer below:
1) Is the hope that Verdiperstat can stop the progession of MSA?
2) Is the hope that Verdiperstat can reverse MSA (cure)?
3) Is the hope that Verdiperstat will be effective with those who are in the late stage of MSA?
It’s weird that I can’t read anywhere what the expectation of Verdiperstat. I hope it’s not just another band aid pill to help with symptoms while this horrible disease destroys the body.
Hi Mic,
We are in the process of compiling questions for Biohaven to answer. I will make sure your questions are included.
My current understanding is that Verdiperstat is being tried in MSA patients because there were some positive results seen in the MSA mouse model in lab studies. Quoting from the published literature: “MPO inhibition reduces motor impairment and rescues vulnerable neurons in striatum, substantia nigra pars compacta, cerebellar cortex, pontine nuclei, and inferior olives. MPO inhibition is associated with suppression of microglial activation but does not affect 3-NP induced astrogliosis in the same regions. Finally, MPO inhibition results in reduced intracellular aggregates of α-synuclein. This study suggests that MPO inhibition may represent a novel candidate treatment strategy against MSA-like neurodegeneration acting through its anti-inflammatory and anti-oxidative properties.”
See the article here: https://pubmed.ncbi.nlm.nih.gov/22161470/
There is no claim being made that this is a potential cure or reversal of MSA. The hypothesis is that it may slow or stop progression. The phase 3 trial must be completed in order to gather enough data to determine if their hypothesis is correct or not.
Only early stage patients are being included in the current trial so they may not be able to make any claims about efficacy in late stage patients.
If you go to the MSA Coalition’s treatment pipeline page https://www.multiplesystematrophy.org/msa-research/msa-treatment-pipeline/
and click on Disease Modifying Therapies and then click on Verdiperstat you will find links to other background articles on this drug candidate.
Dr. Gregor Wenning, chair of our scientific advisory board, did a presentation at our patient and family conference last year. Verdiperstat was one of the topics. I don’t recall if he mentioned the exact mode of action of this drug but a link to his talk is available at the bottom of our pipeline page. If you advance forward about halfway through his talk you should quickly find his remarks on about a dozen drugs in the MSA treatment pipeline.
You are most welcome to email me for a faster response if you have further questions.
Regards,
Pam Bower
Chair, MSA Coalition Research Committee
pbower@msacoalition.org
I’m a msa patient so I want a complete treatment plan
Hi Mostafa,
Please see our MSA Evaluation and Treatment Guide which can be viewed or downloaded from our website.
https://www.multiplesystematrophy.org/about-msa/
See our resources page for other helpful information.
https://www.multiplesystematrophy.org/msa-resources/
I wanted to bring my mom from China to the US after the COVID-19 crisis, so I can take care of her and seek better treatment plans for her. I checked Biohaven’s early access program for their new MSA drug under investigation. One of the eligibility requirement is that my mom must have a doctor licensed in the US & can directly supervise treatment. Anyone know how I can find a doctor willing to help with this?
I’m her only child. My dad passed away when I was an infant, now I just wanted to try every possibility to save my mom.
With appreciation in advance,
Nan
Hi Nan,
You didn’t say where you were located. You are welcome to contact me by email to discuss. pbower@msacoalition.org
Hi,
My brother was diagnosed with MSA.
He is 59 years old and has two young children aged 9 and 11. We can’t bear the thought of losing him.
We are in Dublin, Ireland.
Is there any way possible we could get this new drug to possibly prolong his life.
I’d appreciate any help you could give me at all.
Thank you so very very much.
Yvonne
Hi Yvonne,
The drug company just provided us with more answers to questions from the MSA community. Please check back at this link.
https://www.multiplesystematrophy.org/blog/biohavens-verdiperstat-receives-fast-track-designation-for-the-treatment-of-multiple-system-atrophy
Nan, there is also a hospital in China that is supposed to be running a trial using Rituximab (Rituxin) on MSA patients.
Is this drup a candidate for use with progressive supranuclear palsy…and if not…why?
Dear Mr. Ludwig,
My understanding is that this drug is targeting abnormal buildup in the brain of the protein alpha-synuclein. This protein does not seem to be involved in PSP. In PSP a different protein called Tau seems to be the culprit.
I am a 63-year-old Japanese woman. I have been diagnosed with MSA-C. Do you have any plans for clinical trials in Japan? Have you heard that a subsidiary of Biohaven in Shanghai is planning a clinical trial in Asia soon?
Dear Motohide, We will add your questions to the list we are compiling for Biohaven. I will let you know if we get an answer.
Vorrei sapere se in Italia c’è qualche ospedale coinvolto in questo studio o in altri studi clinici . Grazie
https://clinicaltrials.gov/ct2/show/NCT03952806
Questi siti in Italia accettano pazienti per il processo:
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico di Milano Recruiting
Milano, Milan, Italy, 20122
Contact: Giulia Lazzeri 39 025 503 3807 giulia.lazzeri@outlook.com
Azienda Univesrita’ Ospedale, Clinica Neurologica Not yet recruiting
Padova, Italy, 35127
Contact: Valentina Misenti 39 049 821 4400 valentina.misenti@unipd.it
A.O.U. San Giovanni di Dio e Ruggi d’Aragona Not yet recruiting
Salerno, Italy, 84100
Contact: Maria Teresa Pellecchia 39 089 673703 mpellecchia@unisa.it
I have an appt at Mayo Clinic in Minnesota next month. Is it too late to be a part of this trial if I’m approved.
Hi Diane
You will need to inquire with the Mayo clinic team regarding the enrollment status of their trial.
My husband is diagnosed with probable MSA and has been thru all available Therapies and treatments. The Biohaven trial closed to enrollment before he completed his testing. We have read the right to try information (early access info) from FDA, Biohaven etc. we are looking at applying for this drug. However, in researching the process it seems that most drug companies don’t approve these requests very often and when they do they charge a lot of money. What we’ve seen may be old info. Can you provide any thoughts or guidance about this process? Thank you- Charlotte
Hi Charlotte,
Biohaven Pharmaceuticals provides detailed information on their expanded access policy at their website. This was recently pointed out to us by a Biohaven representative so I assume it is current information.
https://www.biohavenpharma.com/science-pipeline/resources/early-access-programs
Good luck,
Pam
pbower@msacoalition.org
What is the cost?
We understand the cost is covered by the drug company as the drug is not yet approved to be sold to the public.
Hi guys do
You know if any trials happening in Australia at all?
Hi Donna,
There is research happening in Australia. Watch for news from the drug company Alterity. They completed a phase 1 clinical trial on their drug ATH434, also known as PBT434. We are waiting to hear if they will move forward with a phase 2 trial in Australia.
https://www.prnewswire.com/news/alterity-therapeutics-limited/
See information on the drug ATH434 also known as PBT434 on the MSA Coalition treatment pipeline page: https://www.multiplesystematrophy.org/msa-research/msa-treatment-pipeline/pipeline-disease-modifying-treatments/
Good luck,
Pam
Hi,
My mother has been diagnosed with MSA and had her first onset symptoms three years ago. Her condition is degarding with time, it is affecting her speech, walk, balance and has also lead to vocal cord paralysis (which is very worrying). I would like to know if there is a means of making compassionate use of this drug through a hospital/clinic in Europe. We are from Malta.
Hi Gaynor,
Sorry to hear your mother has MSA. The drug company is very clear that since they operate primarily in the US they can only provide compassionate use to people in the US who are under treatment by a US physician.
Best regards,
Pam
pbower@msacoalition.org
Hi my name is Rod Behrens i have just been diagnosed with MSA , is there a trial going in Australia ? if not is there anyway i can access verdipestat here in Aus ?
Hi Rod,
Verdiperstat is not available yet by prescription. The clinical trial is no longer accepting new patients anywhere in the world. Expanded access is only available to patients in the United States with assistance from a US-based doctor.
Australians should watch for news about the drug ATH434 (formerly called PBT434) which is being developed by Alterity Therapeutics a drug company based in Australia.
To learn more about MSA you can download and read our document “MSA What you need to know” https://www.multiplesystematrophy.org/about-msa
Best regards,
Pam
pbower@msacoalition.org
Thanks a lot Pam i will look into that. cheers Rod.
Why have a law that gives you the right to try a drug that is still in clinical trials, but your physician cannot get it unless it’s FDA approved.