Welcome! In this issue: • From the Registry Director • Profile: Dr. Frank Anania of the FDA • Your Registry Data at Work • PSC Partners Poster Presentation: AASLD Liver Meeting, Nov. 2021 • Three Clinical Trials Currently Recruiting • Three Minutes with Frank Sasinowski • AASLD Patient Track Recap • Update on the ROADMAP Initiative
From the Registry Director
Dear Registry Participant,
The holidays are here and, once again, COVID-19 is affecting our lives in many different ways. Yet, the activity level hasn’t changed in the Registry. Day after day, we welcome new people to the Registry community. We celebrate each new participant and are grateful to each of you for understanding the importance of patient participation in research. We have passed the 2,000 mark!
In this issue, we try to highlight the many new doors your de-identified data has opened. We also show how you’ve helped stimulate and speed up PSC research. We introduce to you one of the regulatory decision-makers, the FDA’s Dr. Frank Anania who assesses the safety and efficacy of new drugs for liver diseases including PSC. We hope that soon he will have plenty of PSC treatments to review! We provide you an example of how your data, featured during a large international hepatology poster session, serves as an effective tool for bringing PSC awareness of this community’s readiness to engage in research. We feature three clinical trials that are actively recruiting PSC patients and share a clip from one of our favorite speakers, Frank Sasinowski, from his keynote speech for the last ROADMAP webinar.
We hope this short clip will inspire you to watch the recording of his whole presentation as well as those of previous ROADMAP webinars. By being in the Registry and updating your health information, you are already part of the solution. I hope you can join the ROADMAP webinars so that, together, we can create a world where a PSC diagnosis comes with a cure.
Wishing you a Merry Christmas, happy holidays, and an uneventful 2022 filled with good news and hope,
Rachel Gomel, Director, PSC Partners Patient Registry
Profile: Dr. Frank Anania of the FDA
Dr. Anania is one of the decision makers in PSC drug approval at the FDA. We invited Dr. Anania to tell us about himself and about the state of PSC drug development. It is our hope that some of the treatments currently being studied in clinical trials will be successful.
Dr. Anania wrote to the PSC Partners Patient Registry team in response to our interview request. He has been with the FDA for three years and currently serves as the deputy director of the newly created Division of Hepatology and Nutrition (DHN) under the leadership of Dr. Joseph Toerner, a regulatory expert on drug safety.
Dr. Anania has been a clinician, professor, and biomedical researcher at Johns Hopkins, the University of Maryland, and, most recently, Emory University, where he conducted research on the mechanisms leading to hepatic fibrosis, specifically NASH. In his career as hepatologist, he writes that he treated many PSC patients and that he is “keenly aware” of the devastating nature of PSC, "a disease whose pathogenesis is little known." He recognizes the serious unmet needs of PSC patients.
Dr. Anania writes that he is personally committed to the development of drugs for all chronic liver diseases, with a special attention to PSC, “in no small part due to [PSC’s] potentially devastating complications and because of the youthful population PSC often afflicts.”
He stresses the importance of conducting basic research in finding effective treatments for PSC and recognizes the challenges presented by knowledge gaps in key areas such as the causes and mechanisms of PSC, genetic risk factors, the role of the gut microbiome, and more. Like PSC researchers and the PSC Partners team, Dr. Anania believes that discovering such information would improve clinical trial design and help identify optimal endpoints* in determining the effectiveness of a drug being trialed for PSC.
PSC Partners, in collaboration with existing clinical registries, is actively in pursuit of solid endpoints. A natural history study project is in the active planning phase and will be the topic of the fourth phase of the ROADMAP webinar series.
We thank Dr. Anania for connecting with the PSC Partners Patient Registry team.
*A clinical endpoint is an outcome that represents direct clinical benefit, such as survival, decreased pain, or the absence of disease. A primary endpoint refers to the main result in a clinical trial that is measured at the end of a study to see if a given treatment worked. A surrogate endpoint is an indicator or sign used in place of another to tell if a treatment works. Surrogate endpoints include an improved symptom or lower biomarker levels. They may be used instead of stronger indicators, such as longer survival or improved quality of life, because the results of the trial can be measured sooner.
Your Registry Data at Work
You may be asking yourself what happens to your Registry data. You’ve completed surveys in the Registry; your responses have been reviewed; you’ve received acknowledgements for your valued participation; and, when you’re a possible match, you may have received our message letting you know that you may be a candidate for a clinical trial.
However, that’s only what you see. What you don’t see is that your de-identified information travels far and in many directions. It is being used for studies or to search for candidates who could be a match for an upcoming clinical trial. Your accessibility and the large number of registry participants allow us to pursue new studies and help researchers with their PSC studies.
2000+ Registry participants empower PSC Partners to get involved at the earliest stages of PSC drug development. In the past few years, drug developers have expressed excitement about the large number of PSC patients who are committed to providing data to PSC research. You give these researchers a powerful message by joining the Registry. The pharmaceutical companies and researchers come to us, confident that we can help them.
The FDA's requirement that drug developers involve patients throughout the drug-development process underscores the value of our community's input. Our recommendations are always welcomed and discussed with us, and many are implemented. In the process, we inform researchers of the challenges patients might face at each step of the trial.
Our team goes over clinical trial protocols with a fine tooth-comb even though they have already received the scrutiny of regulators and clinical-trial experts. But, ultimately, the true patient experts are those affected by PSC, i.e. the potential clinical-trial participants who live with PSC day after day.
Using our patient lens, we review the trial materials, ask questions, and suggest changes. We ask researchers questions like, “How will the patient feel about going to the hospital for injections eight times a month? Can some of the injections be given at the patient’s home?” The requested changes are implemented when possible.
We call attention to ways patients can be protected: “Will a twelve-year-old feel emotionally drained with a two-hour interview for this study and in the absence of a parent?” We suggest that they split the interview. We recommend that the child’s parent be present to make sure the researcher is alerted if the interview becomes too emotionally draining for the child.
We make suggestions on the language used to address patients: “In your communications with trial participants, could you avoid referring to PSC patients as ‘subjects,’ a dehumanizing term?”
We point to ways of making the trial worthwhile to the patient: “It appears that the patients in the trial would be experiencing at least some PSC symptoms. It would mean sacrificing work and family time with a 25% chance of receiving a placebo and not even trying the drug. Would you consider adding an extension study to introduce the drug to patients who took the placebo for four months?”
We make requests to ensure that patients are supported in every possible way: “If special care is required with a rare drug-induced event, will the patient’s physicians be informed and involved, and do you have any model of compensation for lost time resulting from an adverse event?”
With the increase in clinical trials for PSC, we are involved in recruiting Registry participants to clinical trials and studies. One of the major obstacles drug developers face in deciding to study a rare disease such as PSC is the uncertainty of finding enough patients to fill their trial. The Registry reduces their reluctance.
In response to the Registry team’s research requests, you have responded in large numbers:
When asked to participate in a quality-of-life study attached to a clinical trial, 100 applications were submitted overnight.
When your responses were sought in preparation for the PFDD meeting with the FDA, over 400 of you answered the call.
You gave the same enthusiastic response to an invitation to participate in the Brigham and Women's Hospital nutrition study (DINER), which confirmed the PSC community’s enthusiasm to participate in research.
A study on the impact of PSC on pregnancy became a community endeavor. Mothers with PSC who are in the Registry not only responded in large numbers but agreed to invite female family members to serve as controls for the study. The study was quickly populated, and the researchers rapidly gathered the data they needed.
The stronger the response, the more we convince researchers that PSC, though rare, has a patient group that will be easy to locate.
This is a critical time in PSC research. PSC Partners and international patient organizations, the FDA and international regulators, researchers, clinicians, and drug developers are working together to find biomarkers that can gauge the success or failure of a clinical trial conducted for PSC.
As a Registry participant, your role is central to the success of these endeavors. Every step of the way, we must appear in large numbers to show that PSC patients have numerous and very serious unmet needs. The Registry Team is grateful for your responsiveness and for your commitment to find solutions for PSC.
Together, we are creating a world where a PSC diagnosis comes with a cure.
PSC Partners Presents Data at the 2021 AASLD Meeting
Each year, the American Association for the Study of Liver Diseases (AASLD) holds The Liver Meeting, a conference that typically draws over 10,000 clinicians, researchers, drug developers, drug regulators, and patient representatives from around the world.
During this year’s virtual meeting, PSC Partners Director of Research Strategy Ruth-Anne Pai, PhD, presented a poster that highlighted the findings of the October 2020 Patient-Focused Drug Development (PFDD) Forum on PSC. The Our Voices survey in the Registry served to guide the PFDD event with the FDA.
The poster and poster abstract are available on the Impact page of the Registry website and conclude that:
Findings from the Our Voices survey informed the development of the externally-led PFDD Forum for PSC and highlight the need for a more robust, validated Patient Reported Outcome Measure (PROM) for PSC. Overall, our results demonstrate the willingness of the PSC patient community to share experiences and guide the development of PROMs, which requires further perspective and expertise from the PSC research community.
Your Registry data is important! It is analyzed and presented to PSC experts and researchers, who listen and learn from your patient experience and perspective. Your participation makes a difference!
Three PSC Clinical Trials Currently Recruiting
The COVID-19 pandemic has challenged researchers and posed problems in conducting clinical trials and studies. Despite the pandemic, PSC research continues and in fact, exciting studies with innovative patient-friendly protocols are currently underway. Below are three trials that are currently recruiting.
VISTAS: a pruritus drug trial
Relentless itching (pruritus) is one of the most troublesome symptoms that some liver patients experience. Mirum Pharmaceuticals, a California company focusing its efforts on the unmet needs of the rare liver disease community, has already received FDA approval for their new drug Livmarli, which treats severe itch in pediatric patients with Alagille syndrome, another rare liver disorder.
Mirum is hoping to have the same success in the PSC community for the investigational drug volixibat. Over 20 U.S. center sites are enrolling adult PSC patients with pruritus in Mirum’s “VISTAS” study to determine the efficacy and safety of the drug. The trial is a 32-week, double-blind*, placebo-controlled study. Patients will have the potential option to continue with an open-label extension study in which they continue taking volixibat for up to two years.
Mirum is actively recruiting for its clinical trial. If you suffer from pruritus, you may be a candidate for this Phase 2 trial. You can find more information about the Mirum VISTAS study here and here.
Mayo Clinic: oral vancomycin trial
Oral vancomycin normalizes liver enzymes and improves symptoms in some PSC patients. However, it is not FDA-approved for PSC, and small studies have had mixed results. Mayo Clinic has embarked on a larger Phase 2 trial to test the safety and efficacy of oral vancomycin for PSC.
All three Mayo locations - Minnesota, Arizona, and Florida - as well as Arizona State University, are participating in the study. More information about the Mayo vancomycin study is available here.
SPRING: an anti-fibrotic drug trial
As PSC advances, progressive liver fibrosis leads to cirrhosis. Investigators at Chemomab Therapeutics, a clinical-stage biotech company headquartered in Tel Aviv, Israel, is looking for a treatment to improve fibrosis. On December 2, 2021, the company announced that it will soon expand recruitment for its Phase 2 SPRING trial of its interventional drug CM-101 into the U.S.
CM-101 is a first-in-class neutralizing monoclonal antibody† that targets CCL24, a protein found to be overexpressed in fibrotic cells. Preclinical trials have suggested that CCL24 plays an important role in promoting liver fibrosis and inflammation. By targeting and neutralizing this protein, it is hoped that CM-101 will slow fibrosis progression.
The SPRING study of CM-101 for use in PSC is already underway in Israel and Europe, and the U.S. FDA has just cleared the drug for trials in the U.S. Chemomab plans to enroll patients at numerous U.S. sites in the near future. The trial is a double-blind, placebo-controlled, 15-week study designed to evaluate the safety and efficacy of CM-101 in patients with PSC.
Read more about the Chemomab SPRING study here.
These studies have something in common: they need patients to enroll! If you are interested in participating in any of these studies, please click on the links above. Please check the Patient Registry clinical trials page for updates on PSC trials and how to locate trials near you.
* A double-blind study is one in which neither the participants nor the researchers know who is receiving a particular treatment.
† A neutralizing monoclonal antibody is a type of protein that is made in the laboratory and can bind to certain targets in the body, neutralizing their effect.
Three-Minutes with Frank Sasinowski: The Effectiveness of the Patient Voice
Frank Sasinowski was the keynote speaker for the most recent PSC Partners ROADMAP webinar. He spoke passionately about the power of the patient voice. Frank Sasinowski combines extensive FDA experience with a compassionate perspective of the patient. Take three minutes to experience his compelling testimonials of the impact of the patient voice in drug approval for rare diseases.
Frank concludes this video clip with this statement: "I just want to emphasize, whenever you think you are not important, YOU ARE!"
The full video of this ROADMAP meeting is available on demand here.
Patients and Advocates Welcomed to the AASLD Liver Meeting
The American Association for the Study of Liver Diseases (AASLD) had a robust patient program track at its annual Liver Meeting in November, illustrating the trend towards placing higher value on patient experience. Founded in 1950, the AASLD is the leading organization of scientists and health care professionals studying and treating liver disease, and its annual conference typically attracts over 10,000 attendees.
For most of its history, the AASLD has been strictly a professional organization, but in recent years it has enhanced opportunities for patient engagement. This year’s virtual Liver Meeting was the second time that a dedicated patient track was included in the conference programming. Patients were also able to attend most of the professional and scientific sessions if they wished. (PSC Partners has hosted an exhibitor's booth for years. Pictured here from pre-COVID meetings.)
The patient programming included both a range of patient-centric topics and curated disease-centric sessions that distilled key information and takeaways from the scientific sessions, posters, and abstracts. The patient track included 18 sessions; those of particular relevance to the PSC community were:
How Physician-Patient Partnerships Can Improve Liver Disease Care & Research • Making an Impact Where You Are: Patient Voices as a Vehicle for Change • Grit, Grace, Gratitude & Resilience: What You Wish Your Doctors Knew About You • COVID-19 • Nutrition 101 for Patients with Chronic Liver Diseases • Cirrhosis: Improving Quality through Patient Empowerment • Pediatrics and Rare Diseases • Autoimmune Liver Disease • Community Conversations with the American Liver Foundation, Global Liver Alliance, and others • Practice Guidelines Debrief for Patients • Patient Debrief: Topline Clinical Research – What this Means for Patients
Of special note is that new AASLD clinical practice guidelines for PSC are nearing completion. Dr. Christopher Bowlus, the Registry’s scientific advisor, gave a preliminary report on the work of the AASLD PSC guideline committee. The new guidelines, soon to be formally adopted, will give updated recommendations for clinicians treating patients with PSC. The guidelines encompass testing and/or treatment for PSC, associated IBD, recurrent PSC after transplant, cancer surveillance, and intrahepatic cholangiocarcinoma, as well as transplant criteria. The existing guidelines were published in 2010.
The enhanced patient engagement opportunities offered by the AASLD highlight the importance of patient participation.
(Though The Liver Meeting was in November, many of the sessions remain online through February 16, 2022, and registration remains open. Patients, caregivers, and advocates can register on the AASLD site for a fee.)
Update on the ROADMAP Initiative
By now you may be aware of the PSC Partners ROADMAP initiative, a unique webinar series. Designed to expand the patient role in research and drug development, the meetings have afforded an exciting level of increased patient engagement with the professional PSC community.
PSC clinicians, researchers, drug developers, and regulatory agencies are all invited to the webinar meetings and attend alongside the patient community. ROADMAP is an acronym for Research Objectives and Development Meetings to Accelerate Progress, and the webinar series kicked off in April with an introductory meeting that painted the big picture of how patient engagement and collaboration could look in PSC research.
Since then, six more meetings have been held: two focused on patient symptoms, three on research and the first of two on drug development. The sessions are numbered, and those designated as “101” sessions focus mainly on the PSC community, while those numbered “201” or “301” include all stakeholder groups.
The Drug Development 201 meeting, “Our Pursuit of a Cure for PSC: Patient-Focused Drug Development,” will be held on January 11, 2022. Subsequent meetings will focus on natural history studies as a valuable research tool.
Each meeting begins with one or more keynote speakers, followed by small group breakout rooms facilitated by one or more PSC experts. Patients have the rare opportunity to ask questions, suggest research topics, and otherwise engage with PSC thought leaders.
To enhance understanding and provide additional context, written educational materials and short videos, as well as recordings of the webinar presentations, can be found on the PSC Partners ROADMAP page. Register here for the January ROADMAP meeting.
Established in collaboration with the Office of Rare Diseases Research (ORDR), the National Center for Advancing Translational Sciences (NCATS), and the National Institutes of Health (NIH)
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