MASAC Meeting
March 8, 2024
Washington, DC
- Call to Order Dr. Dunn
Dr. Dunn called the meeting to order at 8:01 AM. Members approved the minutes from the previous meeting and the previous teleconference. Dr. Dunn reminded all the members to submit their conflicts of interest forms.
- Chair Report Dr. Dunn
Dr. Dunn shared her report by starting with a history of MASAC. She noted the membership was made up of physicians; scientists; consumers; chairs of the Nursing, Physical Therapy, and Social Work Working Groups; as well as liaison representatives from ATHN, CDC, FDA, HRSA, WFH, and the Canadian Center Directors. She noted that anyone was welcome to join in MASAC activities even if not a member.
Dr. Dunn welcomed new members: Glaivy Batsuli (Stanford), Deron Burton (CDC representative), Miguel Escobar (Houston), Phil Gattone (CEO of NBDF), Magdalena Lewandowska (IHTC), Samuel Petty (NYLI representative), Kathaleen Schnur (SWWG chair), and Kelly Tickle (NWG chair). She thanked the members who recently rolled off MASAC: Penny Smith, Len Valentino, Amy Wilson, and Courtney Thornburg who had a new position.
Dr. Dunn shared progress on the 2022 priorities when she started as chair of MASAC: gene therapy, inhibitors, joint health/pain, access to care/women’s health, and HEDI. For gene therapy, she said gene therapy readiness was completed in March 2023, contraception guidance was added to gene therapy readiness document, and the vaccine update relevant to gene therapy was completed in 2023. For inhibitors, a revision of by-passing agent guidance was completed in March 2023, and for HARP there would be an update during this meeting.
For joint health and pain, she noted the PT document completed in March 2023 and the pain document that was up for action at this meeting. For access to care/women’s health, she noted an update for MASAC Document 264 was on today’s agenda. She noted mental health access was on the agenda today. She said a geriatric working group was started by Dr. Kouides. She did note that the organ transplant access discussion had no progress since the previous meeting. For HEDI, she made sure everyone knew NHF’s HEDI officer continued to review every MASAC document.
- New NBDF CEO Introduction Dr. Dunn
Dr. Dunn introduced NBDF’s new CEO, Phil Gattone, to everyone. She said he was new to this community but had a long history of service to children and families who were living with health conditions.
Mr. Gattone introduced himself. He thanked Len Valentino for his work and for his willingness to continue to work with Pathway to Cures. He thanked everyone for making him feel welcome. He shared personal stories that made him thankful for clinical care, research, and advocacy. He said he looked forward to working together.
- Hemophilia Alliance Mr. Blake
Mr. Blake shared he started with the Hemophilia Alliance in January 2024 as president and CEO. He shared his background of joining the Indiana Hemophilia and Thrombosis Center in 2008 and thanked Amy Shapiro for his introduction and education in bleeding disorders.
He shared accomplishments in 2023: saving $100 million dollars on the purchases of medications through their group purchasing organization, amending their CSL contract to include Hemgenics, and negotiating a contract with BioMarin for Roctavian. He said in 2023 the Hemophilia Alliance gave back more than $3 million dollars to the community in a variety of ways.
Mr. Blake shared plans for 2024. He said there were currently 105 Hemophilia Treatment Center members, and they planned to continue to grow that number. These members were important because it was more opportunity to grow the group purchasing organization. They hoped in 2024 to enhance relationships with manufacturing partners and create dynamic contracts due to continual changes in the marketplace.
Mr. Blake noted that Hemophilia Alliance estimated that nationally HTC pharmacies dispensed about 25-30% of the hemophilia and bleeding disorder drugs on the marketplace. They wanted to continue to work with the member treatment centers and insurance companies to significantly enhance that number.
- Health Equity, Diversity, and Inclusion (HEDI) Update Dr. Norris
Dr. Norris shared there were updates to the language guide, and she was consulting with Kathaleen Schnur and Dr. Lewandowska about including language for the Amish and Mennonite population. She asked MASAC members to contact her to include other categories that should be considered for inclusion. She said she also was seeking feedback on the people with disabilities section. Specifically, she wanted to make sure no disabilities were missing.
Dr. Norris said the HEDI priority list for 2024-2034 included: bilingual/multi-lingual populations; marginalized populations; rural residents/geographically challenged populations; women, girls, and people who have or had the potential to menstruate; and young adults.
- NYLI Activities Update Mr. Petty
Mr. Petty shared an update on NYLI activities. He said NYLI was NBDF’s Youth Leadership Institute and that it exists to give opportunities to youth in the community. He said he had been able to participate as the Research Department’s intern. In doing that, he said he looked over the CVR baseline survey and helped with advertisements. He said he also worked with the virtual advisory panels which allowed community members to advise pharmaceutical companies and NBDF while reviewing educational materials and philosophies.
- Geriatric Working Group Dr. Kouides
Dr. Kouides said he was presenting on behalf of Tyler Buckner, Miguel Escobar, Magdalena Lewandowska, Ming Lim, Mark Reding, Michelle Sholzberg, Maime Thant, and Peter A. Kouides.
He said this working group started with an acknowledgement that the bleeding disorders population was aging and wondering if HTCs include gerontologists/geriatric specialists.
In an overview, he noted there was a growing body of literature in the geriatric people with hemophilia particularly concerning bone health, cancer screening in seropositive HBV/HCV PWH, cardiovascular disease, and pharmacological management.
He said there was less data on depression, dementia, reduced mobility and dexterity, reduced access to skilled nursing facilities, and recommendations for prophylaxis for specific geriatric screening.
Dr. Kouides shared cardiovascular questions in the aging person with hemophilia including natural anticoagulation, the FVIII/FIX threshold to safely start aspirin or oral anticoagulation in PWH, the bleeding risk in PWH using antiplatelet or oral anticoagulant therapy, if clotting factor prophylaxis be adapted in PWH in need for anticoagulation therapy, if the decision for oral anticoagulation in PWH has been made, if the advent of emicizumab and efanesoctocog alfa suggest a safe threshold for antithrombotic therapy.
For pharmacological management in the aging population, he said they were reviewing pain management- non-opiate and opiate based, prophylaxis for spinal/epidural injections, spinal cord stimulator, and polypharmacy with focus on medications in the older patient that may increase bleed risk.
Dr. Kouides shared they hoped the document would not be long but would be practical.
- NBDF Educational Programs Ms. Hayes, Ms. Hicks
Ms. Hayes said the presentation would provide an overview of 2023. She said there were 12,814 education publications distributed, 367,644 consumer web visits, and 1,960 attendees at live workshops, events, and webinars.
Ms. Hayes said there was a focus on HEDI in 2023 including six HEDI champions in education, translation of content into Spanish, revamping materials to increase accessibility of information for consumers, WGPPM Summit, and travel grants.
For the clotting cascade video series, she said the videos were viewed more than 45K times, the. She added the next would be focused on gene therapy. She said plans for 2025 included 3D videos on rebalancing agents and VWD pending budget.
In the area of MASAC for You, she said an ongoing project was to ensure important info in the guidelines was accessible to consumers; MASAC 265 will be completed end of quarter one; Spanish translations; promotion via social media, events, and HTCs; bispecific antibody treatment in progress; and more treatment focused documents planned for 2025.
For 2023 Education for Empowerment Workshops at Chapters, they said 57 workshops were facilitated in-person serving 21 chapters with 949 total attendees.
For the Own Your Path program, they said there was an app-based program to increase adherence to prophy treatment; a program to teach participants how to overcome obstacles; and education, connection, support, and participation incentives.
For the THRIVE campaign, they said in collaboration with the CDC as part of the cooperative agreement, the program was developed. It was part of the inhibitor consumer focus area. They said the campaign would launch in April 2024. They said inhibitor messaging was embedded within a larger message to encourage healthy living with a bleeding disorder.
The 6 Steps to Living Healthy with a Bleeding Disorder was discussed, and they said a campaign would utilize diverse channels and tactics to disseminate the message. Detailed information and resources would be provided for each of the THRIVE steps.
Inhibitor information on hemophilia.org was also updated and re-designed.
- Pain Working Group Update and Physical Therapy Pain Document for Action Dr. Buckner
Dr. Buckner thanked the pain working group members and the members of the Physical Therapy Working Group who worked on the document with multiple efforts from the educational front and the documents for MASAC consideration. For this meeting, Dr. Buckner focused on the physical therapy management document for chronic pain. He said it had minor suggested edits from the previously submitted document, and his goal was to submit it for a vote as an official recommendation. He reminded everyone the document resulted from a thorough review of literature based on pain in people with bleeding disorders and physical therapy interventions. He noted there were several aspects of education related to pain included as treatment, and he said that was a standard multidisciplinary approach to pain management.
Dr. Buckner asked for any questions or discussion. Dr. Dunn asked for any information about the percentage of people in the community dealing with these issues. Mr. Skinner said there had been many qualitative studies done, and the numbers of people with severe hemophilia dealing with chronic pain rated in the 80%-plus range.
MASAC approved Document #283 - "Physical Therapy Management of People with Bleeding Disorders and Chronic Pain.”
- Emicizumab: Low Dose or Non-Standard Interval Doses Dr. Iorio
Dr. Iorio stressed that emicizumab had revolutionized the management of hemophilia A and was a pure breakthrough innovation. He cited clinical evidence. He said using lower dosing of emicizumab provided most patients full protection. He noted low dose emicizumab was not like low dose factor concentrates. He stressed low dose emicizumab provided better protection that standard level factor concentrate.
Dr. Iorio shared additional observations including linearity in dosing was in line with frequency, a lower dose may be protective, and plasma level versus activity showed an opportunity to finding the optimal dose for individual patients.
Implications included linearity of the dose-response and the fact that a lower dose might be sufficient.
Dr. Iorio shared a pilot study from India showing low dose emicizumab prophylaxis in hemophilia A patients. Outcomes were that the patients were contacted every month for bleeding assessment and adverse events, there were annualized bleed rates (ABR), annualized joint bleed rates (AJBR) were calculated, and emicizumab concentrations were measured before seven and 14 days after infusion.
To address if emicizumab was needed, Dr. Iorio shared data that showed in the early emicizumab program one patient group (n = 6) with a low dose (0.3 mg/kg/week) significantly improved annual bleeding rate (ABR) (from 32 to 4); higher doses (1 and 3 mg/kg) lead to 0 bleeds. He added that in a Japanese study the lowest dose of emicizumab produced a plasma concentration equal to 25% (i.e., 10 µg/ml) of the currently recommended dose.
- Recommendation on Shared Decision-Making Dr. Escobar, Dr. Thornburg
Dr. Escobar spoke about the Shared Decision-Making tool that was developed by the Word Federation of Hemophilia. He said Shared Decision-Making (SDM) is a process in which healthcare teams and people with hemophilia and their caregivers work together to make treatment decisions based on clinical evidence that balances risks and benefits with patient preferences and values in mind.
He said the WFH SDM tool is an interactive, web-based platform designed to guide PWH/caregivers and their health care team, through the process of making an informed and shared treatment decision. He said it provided users with the tools and knowledge needed to be part of that discussion. The information in the SDM Tool is also useful for decisions related to treatment selection in a formulary and for advocating for expanded access to treatments.
He said benefits included building patient trust, rapport, and confidence; alignment of treatment plans and patient values; prevention of miscommunication; efficient use of healthcare resources; professional satisfaction; improved satisfaction; enhanced understanding of treatment options; increased adherence; and improved health outcomes.
Dr. Escobar said the WFH tool did not include on-demand treatment regimes. He said the tool was evidence-based, had up-to-date evidence, and would be updated regularly.
Dr. Dunn shared a desire that MASAC make a recommendation to encourage people to use the tool with their patients and offer the WFH version as an option of a tool to use. She called the members’ attention to the draft statement that was provided. Dr. Meeks suggested a line be added that MASAC encouraged the development of tools for the non-hemophilia population but for all bleeding disorders. Dr. Dunn noted the proposed document was generic. Dr. Pierce noted comorbidities should be included in promoting this approach. With other comments, Dr. Dunn suggested the draft be reviewed during lunch to be presented again later in the meeting.
- MASACRecommendations Concerning Products Licensed for the Treatment of Hemophilia and Selected Disorders of the Coagulation System Dr. Buckner
Dr. Buckner shared proposed updates to MASAC Document #280. He said one change to propose was a new label indication for plasma derived Wilate. He said based on new data the label had an addition for routine prophylaxis. He proposed adding a sentence that stated, “One plasma-derived product is approved for routine prophylaxis in children 6 years of age and older and adults with VWD.”
He said other changes would be pending decisions from FDA about accepting possible new gene therapy products.
Dr. Buckner asked MASAC to consider a future brief statement regarding the use of emicizumab in the acquired hemophilia A population. He said a review of data would be needed.
During a discussion about off-label use of medications, Dr. Dunn noted that for this document, labeled indications were the goal, but there may be other mechanisms in the future for discussing off-label uses that had information about safety and efficacy. Others agreed uses should follow FDA directions. She said a working group would be needed for research. Dr. Buckner asked if there were any existing working groups that could address these off-label uses, and the response was there were none. Dr. Dunn asked for volunteers for a new working group to address off-label use of products. Dr. Buckner suggested soliciting volunteers after the meeting by email. Dr. Dunn suggested obtaining feedback on this after THSNA and including that community.
Dr. Buckner noted the document was currently organized by diagnoses and available treatment options even though some products were marketed as extended half-life products, and that might be discussed in a future version.
After review, MASAC approved Document #284 – “MASAC Recommendations Concerning Products Licensed for the Treatment of Hemophilia and Selected Disorders of the Coagulation System.”
- Gene Therapy Lexicon Dr. Staber, Dr. Roberts
Dr. Staber said a group was proposing a MASAC recommendation regarding lexicon development for gene therapy. She said it would be helpful in discussions among healthcare providers. She added this included anything that could be done such as gene addition, gene correction, gene editing, and anything given to a cell to alter the DNA.
Later in the meeting, MASAC approved Document #285 – “MASAC Recommendation Regarding the Need for Bleeding Disorders Gene Therapy Lexicon Development.”
- NBDF Update Ms. Rotellini
Ms. Rotellini shared an update for the Unite for Bleeding Disorders Walk. She said the 2023 walk season closed out with a total of 38 walks, 5,890 participants, and $2.02 million raised.
She shared NBDF hosted the annual Unite for Bleeding Disorders Awards Ceremony with nine chapters winning the Rising Star Chapter designation by hitting three of the five key performance benchmarks. 10 chapters won Star Chapter hitting 4 of our 5 key performance benchmarks, and Asociación Puertorriqueña de Hemofilia y Condiciones de Sangrado was named Chapter of the Year.
The Our HTC Challenge in partnership with the Hemophilia Alliance continued to help increase HTC engagement within the walk program. 42 HTC teams had a combined 402 HTC team members and raised a total of $41,305 to support their local bleeding disorders communities.
Ms. Rotellini said strategic planning calls were held with Virginia Hemophilia Foundation, Gateway Hemophilia Association, and Asociación Puertorriqueña de Hemofilia y Condiciones de Sangrado. Oklahoma Hemophilia Foundation and Guam Community Outreach had calls planned.
For the chapter webinar series, Chapter Services hosted four webinars available to staff in Q4 of 2023. Over the four webinars, there were a total of 127 cumulative participants.
A 3-day, chapter training opportunity was held in Seattle, WA with over 20 informational sessions regarding best practices, innovative problem solving, and engaging the community. There were 136 total attendees (81 Chapter staff, 25 Industry, 25 NBDF staff, 4 BODs & speakers).
In 2023, 12,814 education publications were distributed, there were 367,644 consumer web visits, and 1,960 Attendees at live workshops/events/webinars.
The focus on HEDI in 2023 included six HEDI champions within education, significant translation of content into Spanish, revamping materials to increase accessibility of information for consumers, the WGPPM Summit, and travel grants. She stressed that HEDI was woven throughout all NBDF did.
She said Own Your Path Program participant recruitment resulted in ten HTC and chapter partners, an HFA conference booth, the HELLO Summit, and the Bleeding Disorders Conference in National Harbor, MD.
HANDI’s fourth quarter saw 2,471 total HANDI Users, 1,417 HANDI main page views, 1,942 Scholarships page views, and 278 HANDI FAQs total page views.
- Accessing Factor XI Concentrate Dr. Roberts, Dr. Singleton
Dr. Roberts addressed factor 11/hemophilia C. He said the prevalence of F11 from ATHN in the latest ADS (data through February 2024) showed 787 participants had "Factor XI, hereditary" recorded as their primary diagnosis with the incidence being 1/100,000 in the U.S.
Traditional treatment modalities for FXI deficiency (UK prevalence 400 cases) include antifibrinolytics, desmopressin, fresh frozen plasma (FFP) and FXI concentrates, but there had been reluctance to use FXI concentrates because of reported incidence rates of thrombosis up to 10%. He said HEMOLEVEN was a human plasma-derived factor XI concentrate available in France since 1992, but there were few data regarding its use by physicians. There were FXI levels of approximately 30–40% (0.3–0.4 IU mL−1 of plasma). Normal recovery was estimated at 2 U dL−1 per U kg−1.
Dr. Roberts said this discussion arose because he had a colleague who heard he had a factor XI-deficient patient and wondered if factor XI concentrate was available. He said the only one he knew of was Hemoleven made by LFB.
Dr. Roberts said there were no plans to approve the product in the United States, and the intent was to bring this to MASAC’s attention. He asked for comments.
Dr. Dunn noted that through ATHN it was known where the patients were who were diagnosed and might be ripe for an investigator initiative.
Dr. Singleton acknowledged the data could be included in the ATHN dataset, but there was no funding to support the analysis at the time. She did add the data would remain in the dataset for future use.
When asked, Dr. Roberts shared the product was currently only approved in France so Dr. Pierce suggested this would be an opportunity to collaborate with the EHC and EAHAD to develop a joint communication. Dr. Pierce suggesting drafting a recommendation to move this forward.
Dr. Dunn said the issue was right for a MASAC recommendation that WFH and other colleagues could use.
- NBDF Research Update Ms. Willey, Dr. Santaella
Dr. Santaella shared an update of the National Research Blueprint. She said the first phase of the national blueprint started in 2020 with a comprehensive assessment of the State of the Science. It involved hundreds of people in and out of the community looking for gaps in knowledge and literature. She said the output was a list of prioritized research questions developed by the community. The lived experience experts (LEEs) were the key stakeholders. The findings were presented in 2021, and articles were published in 2023.
She said phase 2 was in 2022 and continued to 2024 to develop the National Research Blueprint with the output being a comprehensive plan that integrated the LEEs as key members of the research team and grounded the research process in HEDI principles. The initial draft was presented at the NRB Summit in January 2024. The attendance was 72.
She said phase 3 started in 2023 and was implemented as an effort coordinated by NBDF with a Plan for strategic meetings with potential collaborators.
Ms. Willey shared updates from Pathway to Cures. She said Pathway to Cures existed to support NBDF in enabling cures for inheritable blood and bleeding disorders and to address and prevent the complications of these disorders. Furthermore, she added a goal to create future revenue sources to assure NBDF continued to support the blood and bleeding disorders community through innovation advocacy and research. She said the goals were to promote first-in-class therapeutics; novel, precision diagnostics, including biomarkers; and novel technologies.
Ms. Willey shared the most recent venture fund update was from FiveLiters, a bleeding disorders-focused affiliate of Spark BioMedical. Ms. Willey said progress and accomplishments included $3.5 million funds under management, 114 companies reviewed, $750,000 invested and $12 million raised by portfolio companies. She said 2.5 full time dedicated staff were working.
- MASAC Guidance for Genetic Testing for Non-Hemophilia Disorders Dr. Singleton
Dr. Dunn welcomed Dr. Singleton and noted MASAC did a great job recommending genotyping for persons who might be affected by hemophilia, but a suggestion was received to also address the non-hemophilia conditions.
Dr. Singleton said she was happy to chair this subgroup. She said their charge was to establish guidance for MASAC. She said it started focused on how they could provide guidance to better understand the biology of non-hemophilia disorders and improve the ability to diagnose these disorders using genetic testing. She added that as a committee they identified priorities with this charge to be make or refine the diagnosis, predict severity, determine risk, identify genetic carriers, help with reproductive counseling and birth planning, and lead to improved, individualized treatments.
Initial MASAC Working Group Recommendations included recommending universal testing for all individuals with clinical bleeding and a confirmed bleeding disorder.
She said Genetic counseling with testing was also recommended for education and anticipatory guidance. She said advanced genetic testing could provide diagnostic confirmation, avoid unnecessary or inappropriate therapies, predict severity the condition, provide a better understanding of molecular pathology, leading to an improved diagnostic process and individualized treatments that can benefit the patient/individual and the healthcare system.
Dr. Singleton suggested goals should be to make recommendations that are supported strongly with evidence and stand the test of time, and to provide conservative recommendations that stand on very firm footing. She said they could be aspirational but needed references to support claims and that literature was needed for almost every sentence. She said they wanted to have recommendations on genetic testing and a call to action.
Dr. Singleton said next steps should include guidance for genetic testing for non-hemophilia disorders with follow-up meetings to review available data, inviting additional committee members, and finalizing recommendations for presentation during the next MASAC meeting.
Dr. Dunn offered to share an LEE with Dr. Singleton for her team.
- Use of Coagulation Factor Assays to Monitor Clotting Factor Concentrate Replacement Therapy in Hemophilia A and B: Guidance for Laboratories Dr. Meeks
Dr. Meeks shared proposed updates to MASAC Document #228 – “Statement Regarding Use of Various Clotting Factor Assays to Monitor Factor Replacement Therapy.”
She said the previous version of the document was approved at a time when some of the extended half-life modified factor concentrate products were reaching the market. She said it was a document that said labs should add chromogenic assays to their portfolios. She said that with Altuviiio coming to the market with a need for on-stage testing it was a time to revise the document, and through that process it was decided this entire document was out of date.
She included feedback since the last meeting and added three recommendations that were from laboratories routinely performing coagulation factor assays on patients with hemophilia suggesting they should strongly consider having available both one-stage and chromogenic FVIII and FIX assays, laboratories routinely performing coagulation factor assays should participate in regular proficiency testing exercises available through national and international coagulation quality organizations such as the North American Specialized Coagulation Laboratory Association, and laboratories routinely performing coagulation factor assays should strongly consider participating in field studies of these concentrates or manufacturer provided samples spiked with known quantities of a specific product to evaluate the performance of the local laboratory testing platforms.
Dr. Meeks shared the plan to share this with other doctors who direct special coagulation laboratories.
Dr. Pierce recommended three advisors: Elaine Gray from the UK, Steve Kitchen from the UK, and Rodney Camire at CHOP. Dr. Davila suggested asking Dr. Allison Wheeler from Vanderbilt to be involved.
When Dr. Meeks asked if this document should be restricted to measuring factor 8 and factor 9 levels in treatment to add some information about gene therapy without the need for an entire new document, MASAC agreed. Dr. Meeks said she would change the title to reference gene therapy and then present the document to MASAC.
19. HARP Update Dr. Meeks
Dr. Meeks said from the NHLBI-funded side of HARP (Hemophilia A Research Program) which started from the State of the Science was an intergenerational cohort study that was collecting samples for future use. She said good progress had been made on the research side. She said they had a first-round protocol that received IRB approval. She added they were starting to prototype the best way to collect and store samples.
Dr. Meeks hoped by the next MASAC meeting to have an update.
20. Document #264 Update: MASAC Recommendations Regarding Diagnosis and Management of Inherited Bleeding Disorders in Girls and Women with Personal and Family History of Bleeding Dr. Baldwin
Dr. Baldwin presented updates to Document #264 – “MASAC Recommendations Regarding Diagnosis and Management of Inherited Bleeding Disorders in Girls and Women with Personal and Family History of Bleeding” She thanked Rose Bender, Peter Kouides, and Jennifer Davila for contributing to the edits for this document.
Dr. Baldwin said the initial intent was just to update the document, but some areas deserved more edits. She said some areas became more specific including screening and she asked MASAC’s opinion about keeping the document specificity as opposed to refereeing to a specific screening program.
She said the terminology in the document was changed from “girls and women” to “people who menstruate.” They also added the importance of screening in treatment for iron deficiency and the importance of screening of connective tissue disorder.
Dr. Baldwin pointed out the document defined two main timepoints to focus on screening for heavy menstrual bleeding and obstetric bleeding.
She said some instruction on diagnostic evaluation was added including what the basic evaluation should include.
For access, she said they added, “HTCs should take an active role in advocating for financial access to off-label medications and access to a full range of options for evidence-based reproductive healthcare, including contraception, gender-affirming hormone therapy, induced abortion, and fertility treatments. HTCs should advocate for removing barriers to optimal care, including improving geographic access to obstetric care.”
After discussion, MASAC approved Document #286 – “MASAC Recommendations Regarding Diagnosis and Management of Inherited Bleeding Disorders in Girls and Women with Personal and Family History of Bleeding.”
21. Access to Mental Health Services Document and Mental Health Working Group Dr. Reding
Dr. Reding presented a draft outline of “MASAC Statement on Reducing Barriers to Mental Health Treatment Facilities and Programs for Persons with Bleeding Disorders.” He said the already-approved substance abuse document was used as a base for this draft. He said the draft would be further refined, and he hoped it would be ready for a vote from MASAC at the next meeting.
To add to the SUD document, he said they added, “If the bleeding disorder treatment team recommended prophylaxis but the person with a bleeding disorder chooses on-demand treatment instead, the individual may be considered stable if they have the knowledge, access, and ability to successfully treat bleeding events on-demand.”
Dr. Reding said, considerations for people with co-occurring bleeding disorders and mental health issues included self-infusion/injection for PwBD, use of mental health medications that have potential impacts on coagulation for PwBD, crisis intervention techniques for PwBD including physical holds and restraints, emergency use of intramuscular injections, self-injury, electroconvulsive therapy, and recommendations for the emergency action plan.
Dr. Reding said the mental health team should consider the PwBD’s mental state, whether the PwBD has expressed intent to utilize BD supplies to harm self or others, whether the PwBD has demonstrated safe behaviors, and desire and willingness to do the infusion/injection.
Dr. Reding said other mental health medications with potential impacts on coagulation should include selective serotonin reuptake inhibitors, valproic acid, psychotropic medications that include risk of liver dysfunction including first generation phenothiazines and atypical antipsychotics.
Dr. Reding emphasized that despite the potential impacts, people with bleeding disorders should be prescribed the most appropriate products for their mental health condition based on the recommendation of the person’s psychiatric team. However, he said the group recommended the psychiatric team consult and discuss appropriate/relevant monitoring with the bleeding disorders treatment team prior to prescribing such medications.
Dr. Reding addressed physical holds and restraints by saying the use of physical holds and restraints had potential risk of bleeding related injuries, and that despite these potential risks, mental health facilities should use their standard crisis intervention techniques with people with bleeding disorders per behavioral health team and institutional policy, and after the use of physical holds or restraints, the post-crisis assessment should include a consultation with the bleeding disorders treatment team and the implementation of the person’s bleeding disorder emergency action plan, if appropriate.
For the approach to intramuscular injections, Dr. Reding listed that they recommend that the mental health facility staff discuss the plan for administration of intramuscular injections with the bleeding disorders treatment team and incorporate any recommendations into the emergency action plan upon admission. He also said they recommended the bleeding disorders treatment team consider MASAC Document #278 on the administration of vaccines when making recommendations to the mental health facility staff on the use of intramuscular injections.
Dr. Reding went on to say the group specifically recommend the staff use the smallest caliber needle recommended for the medication, apply firm pressure to the site for at least 2 minutes without rubbing, watch for hematoma development at the injection site, and depending on the PwBD’s factor level, use therapy to prevent hematoma formation for planned intramuscular injections.
Dr. Reding highlighted the statement that recommended the mental health facility staff discuss self-injury with the person’s bleeding disorder treatment team to discuss whether further assessment and/or treatment may be appropriate.
For the use of longer-acting products, Dr. Reding read the line, “If the co-occurring mental health condition makes regular infusions or injections challenging, the BD treatment team should consider recommending that the PwBD switch to a longer-acting hemostatic product,” and asked MASAC for feedback.
Dr. Reding asked anyone with refence suggestions for the document to contact him and to expect to vote on a final document at the next MASAC meeting.
22. Bone Health Task Force Document for Feedback Ms. Joyner
Ms. Joyner asked for feedback on the document she presented before the task force proceeded. She shared from the bone health task force of the PTWG the Physical therapy management for bone health in people with bleeding disorders.
She said the rationale and scope included that people with bleeding disorders were a specific population known to have increased risk for bone health conditions compared to the average person. As the medical management of bleeding disorders improves over time, people with them were living longer, and the need for surveillance of bone health over the course of their lives was imperative to maintaining a safe and healthy lifestyle.
She said the purpose of this document was to provide practical guidance to physical therapists who provide care to people with bleeding disorders and that the physical therapy task force developed physical therapy specific recommendations for the assessment and management of bone health in people with bleeding disorders.
Ms. Joyner said in the document they planned to include a similar outline to the pain document including background, rationale, scope and audience, and methods and process. She said recommendations included general considerations, and medical management outside of the Scope of PT Statement. She said PT statements were to include assessments (risk factors of bone health, assessment of fall risk, and assessment of fracture risk), interventions (education, prevention, therapeutic exercise, and therapeutic Modalities), therapeutic exercise (aerobic exercise, strength training, and balance), and therapeutic Modalities (pulsed electromagnetic fields and vibration plate).
She said the next steps were to add more than just the PT management/recommendations for bone health for PWBD. She said the PTWG task force wanted to emphasize the need for a medical management companion document.
Ms. Joyner said they planned to have the document ready for approval at the next MASAC meeting.
23. Advocacy Update Mr. Schaefer
Mr. Schaefer shared advocacy updates. He started with Washington Days by saying 428 participants registered representing 45 states and Puerto Rico. He said 26 staff, 8 Board Members, and 19 Industry (who did not visit the Hill). He said issues addressed were bleeding disorders awareness month, support policies to protect individuals with bleeding disorders from narrow formularies, and support for H.R. 830 /S. 1375, which was the Help Ensure Lower Patient (HELP) Copays Act.
Mr. Shaefer discussed reasons for formulary changes by saying the plans use formulary exclusions as one negotiating lever for maximizing their revenues from manufacturers whose drugs are included in the formularies. He said recent examples of large-scale exclusions included CVS national formulary excluding all standard half-life and plasma-derived factor IX products, BCBS of Tennessee excluding about 18 bleeding disorders products from formulary in 2023 and again in 2024 and including all available products for certain conditions.
As to why discuss plasma and bleeding disorders now he said plasma-derived therapies still played a major role in bleeding disorders treatment and health equity. He added that NBDF’s historical commitment to blood and product safety, supply and access had not changed.
Mr. Shaefer said APLUS recent and future initiatives included weighing in as a coalition on three congressional caucus briefings, state policy about plasma donation, FDA MSM donation policy, and working with partners in industry to find a common mission.
He invited anyone to contact him with questions.
24.WFH Update Dr. Pierce, Mr. Skinner
Dr. Pierce shared the stance that the global hemophilia community was under assault due to initiatives undergone in the previous six months. He said one was from WHO recommending cryoprecipitate products for the treatment of hemophilia A, and the other was new ISTH guidelines that were drafted the previous October.
Dr. Pierce shared the background for the ISTH guidelines that he felt brought care back to a 1990s level of treatment and reversed the process started more than 10 before for prophylaxis; higher trough levels; EHL products, UHL product, FVIII mimetics, anti-TFPI products; inhibitor patient bleed control; newborn bleed control, and a goal of zero bleeds. He noted these advanced helped the 15% of the population with access, but WFH was continually struggling with rest of the world to get products into other countries.
The timeline for the new ISTH guidelines started a few years prior as an anonymous, autonomous committee. They were first published October 2023, and they received 400+ comments from global community by deadline of November 5, 2023. The comments generally pointed out the guidelines were not all encompassing, and the positions were controversial especially in the use of plasma-derived factor 8 and decreased use of emicizumab.
Dr. Pierce said ISTH used the GRADE process, which is rigorous but designed for large, blinded placebo-controlled studies instead of clinical studies. He felt this resulted in weak to very weak evidence to support most of the 13 recommendations, and the methodology in the absence of context was dangerous.
Dr. Pierce reported that multiple individuals and organizations submitted comments by the November 5 deadline, but ISTH was silent and did not respond to a WFH letter listing concerns. Another letter was sent December 2023 from WFH, EHC, EAHAD, NBDF, and AHAD-AP that focused on impact on low- and middle-income countries where health ministries look to spend less, not more money, on hemophilia therapies. It also pointed out that weak to very weak evidence for emicizumab, EHLs, etc. conflicted with WFH Guidelines 2020 and all efforts by many groups to introduce improved therapies into countries. They asked ISTH to halt the project. An ISTH response to this letter sent Feb 2024 was dismissive of all concerns.
A second letter from WFH, EHC, EAHAD, NBDF, and AHAD-AP was sent in February in response to the ISTH reply. They pointed to damage these guidelines would cause in countries that will use them to continue to purchase plasma-derived and early generation conventional recombinant products. Another ISTH response in late February 2024 was again dismissive and did not acknowledge the human impact.
Dr. Pierce said they were setting up a call for country and regional hemophilia medical societies, some NMOs, to participate March 15, 2024. The assumption was the guidelines would likely be published in JTH or RPTH and discussed in multiple forums at ISTH in Bangkok in June 2024. The other organizations were asking those editors for space to comment.
Dr. Pierce said a fundamental problem was that Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was an inappropriate guideline process to use for rare diseases since sometimes a guideline panel might judge the certainty that the desirable effects of an intervention clearly outweigh its undesirable effects as high, but the body of supportive evidence was indirect. He said instead the GRADE working group recommended developing ungraded best or good practice statement (GPS) and developed guidance under which circumstances they would be appropriate.
Dr. Dunn shared the concern that these guidelines would be published soon and have a negative impact on the community. She said MASAC should issue a resolution to support the efforts. Dr. Pierce read the draft resolution.
After discussion and suggestions for references to list in the document, MASAC approved Document #288 – “MASAC Resolution on Proposed Hemophilia Treatment Guidelines from the International Society on Thrombosis and Haemostasis (ISTH).”
Mr. Skinner shared suggested edits to MASAC Document #149 – “MASAC Recommendation on the World Health Organization Essential Drug List.”
Mr. Skinner reminded everyone that the World Health Organization maintained a list of essential medicines they believed were important for national governments to purchase as part of their national health system to ensure public health. The list was built in two tiers: a core list and a complementary list. He said it was an ongoing conversation with WHO that hemophilia products remained on the list. However, he said that in 2023, changes, the coagulation factors were left on the complementary list, but cryoprecipitate (both pathogen inactivated and non-pathogen inactivated) made it to the core list, resulting in deep concern in the bleeding disorders community. Appeals were made, but WHO said to submit comments again in 2025. Mr. Skinner said the important point was that some governments could choose to prioritize cryoprecipitate over clotting factor concentrate along with the potential consequences of viral infection around the world.
Mr. Skinner shared the proposed changes to the document to stress the needs of the bleeding disorder community to WHO. The changes included language that WHO should follow their previously well-established principles for accessibility, efficacy, and safety for many drugs.
After discussion, MASAC approved Document #287 – “Resolution on the World Health Organization Essential Medicine List.”
25.ATHN Update Dr. Singleton
Dr. Chrisentery-Singleton shared an update from ATHN.
She said the ATHN Support and Grants showed 3,075 ATHN Support requests fulfilled, 123 ATHN Support training sessions conducted, and 50 DQC grants awarded.
Dr. Singleton said the ATHN Data Summit 2023 had 377 in-person attendees, 30 presentations, 15 partner exhibits, and 29 posters.
She discussed ATHN 16: Safety of SEVENFACT® for the Treatment of Bleeding Events in Patients with Hemophilia A or B with Inhibitors. Principal Investigators were Dr. Chrisentery-Singleton and Dr. Reding. She said ATHN 16 was a phase IV multi-center, open-label, safety study. ATHN 16 aimed to evaluate the safety of the FDA-approved drug SEVENFACT® when used to treat bleeding episodes in participants with hemophilia A or B with inhibitors who were being treated either with or without prophylactic agents.
She said the ATHN 16 primary objective was to evaluate the safety of SEVENFACT® when used to treat bleeding episodes in participants with hemophilia A or B with inhibitors either with or without prophylactic treatment. The primary endpoints were European Haemophilia Safety Surveillance (EUHASS) reportable events, serious adverse events (SAEs), adverse events of special interest (AESIs), and pregnancy.
26. CDC Liaison Dr. Burton
Dr. Burton said CDC’s Division of Blood Disorders had been recently reorganized and was now a slightly broader division called the Division of Blood Disorders and Public Health Genomics. He said that as a new division, there would be a strategic planning process to define priorities and goals. He planned to have more information at the next meeting.
Dr. Burton’s second update was on the community counts inhibitor surveillance report from October 2013 to December 2022. He said the report was in final stages of development. He said the dataset covered about 15,000 persons with hemophilia A and B at US HTCs.
Dr. Burton added that CDC’s main website was undergoing a design change with an effort to make the information more streamlined and accessible.
27. NHLBI Update from Dr. Kindzelski Dr. Dunn
Dr. Dunn said Dr. Kindzelski could not attend the meeting. She said he shared there were not any updates.
28.FDA Update Dr. Kaushal
Dr. Kaushal said recent FDA approvals included Roctavian in June 2023. She said it was a treatment for adults with severe hemophilia A without pre-existing antibodies to adeno-associated virus serotype 5 detected by an FDA-approved test. She said for Roctavian, 112 subjects received a single dose and were followed up to three years post treatment. She said they were all required to be negative for pre-existing Abs to AAV5 using a total Ab assay which was contemporaneously approved with Roctavian. The efficacy was based on ABR; change in the mean ABR in the EEP from a mean baseline ABR of 5.4 bleeds per year to a mean of 2.6 bleeds per year. She said 5 (4%) did not respond and 17 patients (15%) lost response to Roctavian treatment over a median time of 2.3 (range: 1.0 to 3.3) years. The median (Q1, Q3) FVIII activity levels, as assessed by the chromogenic substrate assay, at months 12, 24, and 36 following the treatment with ROCTAVIAN were 24.0 (12.5, 63.7), 12.7 (5.1, 26.5), and 10.0 (4.3, 19.8) IU/dL respectively. Ninety-seven of 112 (87%) efficacy evaluable subjects received immunosuppressive treatment (IS) with corticosteroids or alternate immunosuppressive medications (AIS) to mitigate the immune response to AAV5 capsid (as evidenced by increase in ALT) and to preserve transgene expression. The median range duration of corticosteroid and AIS use was 35 (3.1 to 120) weeks and 26 (6 to 118) weeks respectively. There were no grade 4 or 5 events from the use of immunosuppressive medications.
For other updates, she said HemgenixPMR was ongoing. AltuviiioLab was being monitored for variability of CS/OS ratio is significant in general.
29. New Business Dr. Dunn
With the edits from earlier in the meeting displayed, MASAC approved Document #285 – “MASAC Recommendation Regarding the Need for Bleeding Disorders Gene Therapy Lexicon Development.”
Dr. Dunn asked that the shared decision-making document be reviewed at the next MASAC meeting.
Dr. Dunn thanked everyone for their involvement at the meeting and throughout the year. She recognized MASAC was a volunteer opportunity and a great community.
30. Adjourn Dr. Dunn
Dr. Dunn adjourned the meeting at 5:10 PM.