[Congressional Bills 118th Congress]
[From the U.S. Government Publishing Office]
[S. 543 Introduced in Senate (IS)]

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118th CONGRESS
  1st Session
                                 S. 543

 To increase research, education, and treatment for cerebral cavernous 
                             malformations.


_______________________________________________________________________


                   IN THE SENATE OF THE UNITED STATES

                           February 28, 2023

Mr. Lujan (for himself and Mr. Heinrich) introduced the following bill; 
     which was read twice and referred to the Committee on Health, 
                     Education, Labor, and Pensions

_______________________________________________________________________

                                 A BILL


 
 To increase research, education, and treatment for cerebral cavernous 
                             malformations.

    Be it enacted by the Senate and House of Representatives of the 
United States of America in Congress assembled,

SECTION 1. SHORT TITLE.

    This Act may be cited as the ``Cerebral Cavernous Malformations 
Clinical Awareness, Research, and Education Act of 2023'' or the ``CCM-
CARE Act of 2023''.

SEC. 2. FINDINGS.

    Congress finds as follows:
            (1) Cerebral cavernous malformations (referred to in this 
        section as ``CCM''), also known as cavernous angioma, or 
        cavernoma, is a devastating blood vessel disease characterized 
        by vascular lesions that develop and grow within the brain and 
        spinal cord.
            (2) Detection of CCM lesions is achieved through costly and 
        specialized medical imaging techniques, often not accessible or 
        convenient to patients who need them.
            (3) While CCM is a common type of vascular anomaly, many 
        individuals are not aware they have the disease until the onset 
        of serious clinical symptoms. CCM is often inherited 
        unknowingly.
            (4) CCM affects an estimated 600,000 people in the United 
        States, although fewer than 200,000 are accurately diagnosed.
            (5) Individuals diagnosed with CCM may experience 
        neurological deficits, seizure, stroke, or sudden death.
            (6) Due to limited research, there is currently no 
        treatment for CCM other than brain and spinal surgery, and only 
        for certain patients.
            (7) There is also a shortage of trained physicians to 
        provide skilled and timely diagnosis and appropriate treatment 
        for CCM.
            (8) While the hereditary form of CCM may occur among any 
        ethnicity, the presence of a mutation called the ``common 
        Hispanic mutation'', has passed through 14 or more generations 
        of American descendants from the original Spanish settlers of 
        the Southwest in the 1590s. New Mexico has the highest 
        population density of CCM in the world; Texas, Arizona, and 
        Colorado also have high rates of CCM due to the common Hispanic 
        mutation.
            (9) A second mutation (CCM2 Common Deletion) originating in 
        the Southeastern United States before 1800 has increased rates 
        of the illness in South Carolina, Georgia, Florida, Alabama, 
        Mississippi, Louisiana, Texas, Oklahoma, Kentucky, Kansas, and 
        northern California.

SEC. 3. EXPANSION AND COORDINATION OF ACTIVITIES OF NATIONAL INSTITUTES 
              OF HEALTH WITH RESPECT TO CEREBRAL CAVERNOUS 
              MALFORMATIONS RESEARCH.

    Part B of title IV of the Public Health Service Act (42 U.S.C. 284 
et seq.) is amended by adding at the end the following:

``SEC. 409K. CEREBRAL CAVERNOUS MALFORMATIONS RESEARCH ACTIVITIES.

    ``(a) Expansion and Coordination of Activities.--The Director of 
NIH, in coordination with the directors of the National Institute of 
Neurological Disorders and Stroke, the National Center for Advancing 
Translational Sciences, the National Heart, Lung, and Blood Institute, 
and other national research institutes, as appropriate, for the purpose 
of conducting research and related activities concerning cerebral 
cavernous malformations (referred to in this section as `CCM')--
            ``(1) shall strengthen and coordinate efforts of the 
        National Institutes of Health; and
            ``(2) may award grants and cooperative agreements to public 
        or nonprofit private entities (including State health 
        departments, political subdivisions of States, universities, 
        and other medical or educational entities).
    ``(b) Activities.--The research and related activities described in 
subsection (a) shall include the following:
            ``(1) Clinical, translational, and basic research.--The 
        Director of NIH shall conduct or support, through funding 
        opportunity announcements, grants, or cooperative agreements, 
        basic, clinical, and translational research on CCM, including 
        research on--
                    ``(A) the identification and development of 
                affordable imaging, plasma, and urine biomarkers that 
                fulfill the requirement of the Food and Drug 
                Administration for biomarker qualification as proper 
                measures of CCM pathogenic biology, including 
                diagnosis, response to clinical intervention, or 
                prediction of adverse clinical events;
                    ``(B) pre-clinical trials of promising CCM drug 
                treatment candidates;
                    ``(C) novel biomedical and pharmacological 
                interventions designed to target existing lesions to 
                reduce their size and clinical activity;
                    ``(D) clinical research related to repurposing 
                currently approved drugs for application for CCM 
                treatment;
                    ``(E) development of new non-pharmacological 
                treatment approaches, such as focused ultrasound, and 
                targeted treatment delivery technology;
                    ``(F) the gut-brain axis and the effects of 
                microbiome composition on clinical symptomology;
                    ``(G) the microbiome as a therapeutic target for 
                CCM treatment;
                    ``(H) research related to gene therapy as a 
                treatment for familial CCM;
                    ``(I) research related to RNA-based therapies;
                    ``(J) research related to the mechanistic overlap 
                between CCM and other disorders, including vascular 
                disorders and cancer;
                    ``(K) research related to improving and measuring 
                the quality of life for individuals with CCM and their 
                families;
                    ``(L) contributions of genetic variation to 
                clinical presentation as precision medicine targets for 
                therapy;
                    ``(M) clinical training programs aimed at 
                increasing the number of scientists and clinicians who 
                are trained to treat patients and carry out the 
                research described in this paragraph;
                    ``(N) proteomic, pharmacological, and cell 
                biological analysis of CCM molecules;
                    ``(O) biological mechanisms for lesion genesis, 
                development, and maturation;
                    ``(P) biological mechanisms for lesion bleeding and 
                symptomology;
                    ``(Q) novel biomedical and pharmacological 
                interventions designed to inhibit new lesion 
                development, lesion growth, and lesion bleeding; and
                    ``(R) continued research related to understanding 
                better the natural history and clinical variation 
                associated with CCM, particularly as it relates to the 
                development of drug development tools and clinical 
                outcome assessments.
            ``(2) Facilitation of research resources; clinical trial 
        preparedness.--
                    ``(A) In general.--The Director of NIH shall award 
                grants and contracts to public or nonprofit private 
                entities to fund all or part of the cost of planning, 
                establishing, and providing basic operating support for 
                a network of CCM Clinical Research Centers, including 
                Coordinating and Participating centers regarding 
                research on various forms of CCM.
                    ``(B) Clinical and research coordinating centers.--
                            ``(i) In general.--The Director of NIH 
                        shall build upon the network created by the U01 
                        Clinical Trial Readiness Research Project to 
                        identify and support the development of 2 
                        geographically distributed national clinical 
                        and research coordinating centers with unique 
                        clinical expertise and the potential for 
                        coordinating multisite clinical drug trials 
                        with respect to CCM, including serving as 
                        United States sites in international adaptive 
                        trials.
                            ``(ii) Duties.--The coordinating centers 
                        identified under clause (i) shall provide a 
                        model for the participation centers described 
                        in paragraph (3), facilitate medical research 
                        to develop a cure for CCM, and enhance the 
                        medical care of individuals with CCM 
                        nationwide, including by--
                                    ``(I) maintaining an institutional 
                                infrastructure capable of hosting 
                                clinical trials, facilitating 
                                translational research projects, and 
                                domestic and international 
                                collaborations for clinical trials;
                                    ``(II) implementing the programs 
                                dedicated to patient education, patient 
                                outreach, and awareness developed by 
                                the Cerebral Cavernous Malformations 
                                Consortium under subsection (c)(3)(B);
                                    ``(III) developing the capacity to 
                                establish and maintain communication 
                                with other major CCM research and care 
                                institutions internationally for 
                                information sharing and coordination of 
                                research activities;
                                    ``(IV) demonstrating clinical 
                                expertise in the management of CCM and 
                                appointing a director and support 
                                staff, including a trainee and patient 
                                representative, for CCM research 
                                programming;
                                    ``(V) treating a sufficient number 
                                of eligible patients for participation 
                                with particular focus on unique 
                                subpopulations, such as patients with 
                                the common Hispanic mutation, Ashkenazi 
                                Jewish mutation, CCM2 Common Deletion, 
                                CCM3 gene mutation carriers, or Black 
                                and under-resourced patients; and
                                    ``(VI) maintaining a telehealth 
                                infrastructure to support and provide 
                                clinical consultation for remote and 
                                underserved communities.
            ``(3) Participation centers.--
                    ``(A) In general.--The Director of NIH shall build 
                upon the network created by the U01 Clinical Trial 
                Readiness Research Project to identify and support the 
                development of approximately 6 to 10 clinical and 
                research participation centers to facilitate medical 
                research to develop a cure for CCM and enhance the 
                medical care of individuals with CCM, in partnership 
                with the coordinating centers under paragraph (2) and 
                other national and international entities, as 
                appropriate.
                    ``(B) Eligibility.--To qualify for selection as a 
                participation center under subparagraph (A), an entity 
                shall--
                            ``(i) at the time of selection--
                                    ``(I) be affiliated with an 
                                established research network of the 
                                National Institutes of Health; and
                                    ``(II) have the potential to 
                                participate in a multisite clinical 
                                drug trial with respect to CCM;
                            ``(ii) demonstrate--
                                    ``(I) the capacity to maintain 
                                communication with other major CCM 
                                research and care institutions 
                                internationally for information sharing 
                                and coordination of research 
                                activities, especially through health 
                                information technology; and
                                    ``(II) clinical expertise in CCM 
                                management or complete the CCM clinical 
                                training program under subsection 
                                (c)(4); and
                            ``(iii) have a sufficient number of 
                        eligible patients with CCM.
                    ``(C) Duration of support.--The Director of NIH may 
                provide support for participation centers under this 
                section for a period not to exceed 5 years. The 
                Director of NIH may extend the period of support for a 
                center for one or more additional periods, not to 
                exceed an additional 5 years, if the operations of such 
                center have been reviewed by an appropriate technical 
                and scientific peer review group established by the 
                Director of NIH and if such group has recommended to 
                the Director that such period should be extended.
    ``(c) Cerebral Cavernous Malformations Consortium.--
            ``(1) In general.--The Director of NIH shall build upon the 
        network created by the U01 Clinical Trial Readiness Research 
        Project to convene a Cerebral Cavernous Malformations Research 
        Consortium (referred to in this section as the `consortium').
            ``(2) Membership.--The consortium--
                    ``(A) shall include representatives of--
                            ``(i) the institutions that are part of the 
                        U01 Trial Readiness Project of the National 
                        Institutes of Health, or that are part of other 
                        nationally recognized clinical Centers of 
                        Excellence; and
                            ``(ii) at least 1 national CCM patient 
                        advocacy organization, which may be an entity 
                        that receives a grant or contract under 
                        subsection (b)(2)(A); and
                    ``(B) may include representatives of the National 
                Institutes of Health or the Food and Drug 
                Administration, in an advisory or ex officio role.
            ``(3) Responsibilities.--Through a consensus-based 
        decision-making model, the consortium shall divide assignments 
        and be responsible for--
                    ``(A) developing and implementing training programs 
                for clinicians and scientists in accordance with 
                paragraph (4);
                    ``(B) developing patient education, outreach, and 
                awareness programs and materials, which may be tailored 
                for specific regional or local needs including--
                            ``(i) a regional multimedia public 
                        awareness campaign;
                            ``(ii) patient education materials for 
                        distribution by regional physician and surgeon 
                        offices;
                            ``(iii) an education program for elementary 
                        and secondary school nurses and community 
                        health workers to facilitate early detection 
                        and diagnosis of CCM in areas in which there is 
                        a high density of cases of CCM;
                            ``(iv) regular regional patient and family-
                        oriented educational conferences; and
                            ``(v) nationally relevant electronic health 
                        teaching and communication tools and a network 
                        of professional capacity and patient and family 
                        support; and
                    ``(C) preparing a biannual report to Congress, in 
                accordance with paragraph (5).
            ``(4) Training program for clinicians and scientists.--
                    ``(A) In general.--The consortium shall establish 
                or expand a physician training program, including 
                information and education on advances in the diagnosis 
                and treatment of CCM, and training and continuing 
                education through programs for scientists, physicians, 
                medical students, and other health professionals and 
                care coordinators who provide care for patients with 
                CCM, telehealth, and research relevant to CCM, for the 
                purpose of supporting the development of new centers 
                through educational programming to gain the expertise 
                needed to become clinical and research centers with the 
                potential to participate in clinical drug trials.
                    ``(B) Stipends.--The Director of NIH may provide 
                stipends for health professionals who are enrolled in 
                the training programs described in subparagraph (A).
            ``(5) Report to congress.--The consortium shall biennially 
        submit to the Committee on Health, Education, Labor, and 
        Pensions of the Senate and the Committee on Energy and Commerce 
        of the House of Representatives a report that describes the 
        research, education, and other activities on CCM conducted or 
        supported through the Department of Health and Human Services. 
        Each such report shall include--
                    ``(A) a research plan;
                    ``(B) provisions specifying the amounts expended by 
                the Department of Health and Human Services with 
                respect to various forms of CCM, including those 
                affected by the common Hispanic Mutation, Ashkenazi 
                Jewish mutation, CCM2 Common Deletion, CCM3 gene 
                mutations, and other familial and sporadic forms of 
                cerebral cavernous malformation and patients who 
                identify as Black or African American; and
                    ``(C) recommendations for particular projects or 
                types of projects that the national research institutes 
                or other entities in the field of research should 
                conduct on inherited or non-inherited forms of CCM 
                based on patient-identified priorities.
    ``(d) Prioritize CCM Funding for Biotech.--The Director of NIH, in 
coordination with the directors of the National Institute of 
Neurological Disorders and Stroke, the National Center for Advancing 
Translational Sciences, the National Heart, Lung, and Blood Institute, 
and other national research institutes, as appropriate, shall 
prioritize the provision of grant funding for small biotechnology 
entities that are working to develop treatments for CCM.''.

SEC. 4. CENTERS FOR DISEASE CONTROL AND PREVENTION CEREBRAL CAVERNOUS 
              MALFORMATIONS SURVEILLANCE AND RESEARCH PROGRAMS.

    Part B of title III of the Public Health Service Act (42 U.S.C. 243 
et seq.) is amended by inserting after section 317U the following:

``SEC. 317V. CEREBRAL CAVERNOUS MALFORMATIONS SURVEILLANCE AND RESEARCH 
              PROGRAMS.

    ``(a) In General.--The Secretary, acting through the Director of 
the Centers for Disease Control and Prevention, may award grants in 
such sums as may be necessary and cooperative agreements to public or 
nonprofit private entities (including State health departments, 
political subdivisions of States, universities, and other medical or 
educational entities) for the collection, analysis, and reporting of 
data on cerebral cavernous malformations (referred to in this section 
as `CCM').
    ``(b) National Cerebral Cavernous Malformations Epidemiology 
Program.--The Secretary shall award grants and cooperative agreements, 
including technical assistance, to public or nonprofit private entities 
for--
            ``(1) the collection, analysis, and reporting of data on 
        CCM; and
            ``(2) epidemiological activities, including encouraging 
        consistency in ICD-10 coding, adoption of ICD-11 coding, 
        collecting, and analyzing information on the number, incidence, 
        correlates, and symptoms of cases and the clinical utility of 
        specific practice patterns.
    ``(c) National Surveillance Program.--The Secretary shall--
            ``(1) provide for a national surveillance program for the 
        purpose of carrying out epidemiological activities regarding 
        CCM, including collecting and analyzing information on the 
        number, incidence, correlates, and symptoms of cases of CCM and 
        the clinical utility (including costs and benefits) of specific 
        practice patterns; and
            ``(2) wherever possible, ensure that the surveillance 
        program is coordinated with the data and sample collection 
        activities of the National Institutes of Health under section 
        409K.
    ``(d) Technical Assistance.--In making awards under this section, 
the Secretary may provide direct technical assistance, including 
personnel support.
    ``(e) Coordination With Clinical Centers.--The Secretary shall 
ensure that epidemiological information is made available to clinical 
centers as supported by the Director of the National Institutes of 
Health under section 409K.
    ``(f) Authorization of Appropriations.--There are authorized to be 
appropriated such sums as may be necessary to carry out this 
section.''.

SEC. 5. FOOD AND DRUG ADMINISTRATION CEREBRAL CAVERNOUS MALFORMATIONS 
              CLINICAL TRIAL PREPAREDNESS AND SUPPORT PROGRAM.

    (a) Biomarker Qualification Program.--The Secretary of Health and 
Human Services, acting through the Commissioner of Food and Drugs, 
shall coordinate with clinical centers, investigators, and advocates to 
support the qualification of appropriate imaging, plasma, and urine 
biomarkers for diagnosis and measuring pathology and treatment efficacy 
in an effort to expedite clinical trials for cerebral cavernous 
malformation.
    (b) Clinical Outcome Assessment Qualification.--The Secretary of 
Health and Human Services, acting through the Commissioner of Food and 
Drugs, shall coordinate with clinical centers, investigators, and 
advocates to support the qualification of newly developed patient 
reported outcome measures for quality of life as a clinical outcome in 
an effort to hasten the pace of clinical trials for cerebral cavernous 
malformation.
    (c) Investigational New Drug Application.--The Secretary of Health 
and Human Services, acting through the Commissioner of Food and Drugs, 
shall coordinate with clinical centers, investigators, and advocates to 
support appropriate investigational new drug applications under section 
505(i) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)) 
in an effort to hasten the pace of clinical trials for cerebral 
cavernous malformation.
    (d) Adaptive Trial Design and Expedited Review Pathways.--The 
Secretary of Health and Human Services, acting through the Commissioner 
of Food and Drugs, shall coordinate with clinical centers, 
investigators, and advocates to support domestic and international 
adaptive trial designs for rare disease research and expedited peer 
review mechanisms for including orphan drug designation, fast track, 
breakthrough therapy designation, and priority review or accelerated 
review, where appropriate, in an effort to hasten the pace of clinical 
trials for cerebral cavernous malformation.
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