Notice2026-10268
Notice of Decision Not To Designate Hepatitis Delta Virus Diseases as an Addition to the Current List of Tropical Diseases in the Federal Food, Drug, and Cosmetic Act
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Published
May 22, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
In response to a suggestion by Gilead Sciences, Inc. (Gilead) that was submitted to the public docket FDA-2008-N-0567 on February 14, 2022, the Food and Drug Administration (FDA or Agency) has analyzed whether hepatitis delta virus (HDV) infection meets the statutory criteria for designation as a "tropical disease" under Section 524 of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Specifically, the Agency has analyzed whether there is "no significant market in developed nations" for drugs for HDV infections and whether HDV "disproportionately affects poor and marginalized populations," both of which are statutory criteria for designation as a "tropical disease." At this time, the Agency cannot conclude that HDV infection meets the statutory criteria for addition to the list of tropical diseases under the FD&C Act; therefore, FDA declines to add it to the list of tropical diseases.
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[Federal Register Volume 91, Number 99 (Friday, May 22, 2026)]
[Notices]
[Pages 30312-30318]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-10268]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2008-N-0567]
Notice of Decision Not To Designate Hepatitis Delta Virus
Diseases as an Addition to the Current List of Tropical Diseases in the
Federal Food, Drug, and Cosmetic Act
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: In response to a suggestion by Gilead Sciences, Inc. (Gilead)
that was submitted to the public docket FDA-2008-N-0567 on February 14,
2022, the Food and Drug Administration (FDA or Agency) has analyzed
whether hepatitis delta virus (HDV) infection meets the statutory
criteria for designation as a ``tropical disease'' under Section 524 of
the Federal Food, Drug, and Cosmetic Act (FD&C Act). Specifically, the
Agency has analyzed whether there is ``no significant market in
developed nations'' for drugs for HDV infections and whether HDV
``disproportionately affects poor and marginalized populations,'' both
of which are statutory criteria for designation as a ``tropical
disease.'' At this time, the Agency cannot conclude that HDV infection
meets the statutory criteria for addition to the list of tropical
diseases under the FD&C Act; therefore, FDA declines to add it to the
list of tropical diseases.
DATES: May 22, 2026.
ADDRESSES: Submit electronic comments on additional diseases suggested
for designation to <a href="https://www.regulations.gov">https://www.regulations.gov</a>. Submit written comments
on additional diseases suggested for designation to the Dockets
Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852. All comments should be identified
with the docket number found in brackets in the heading of this
document.
FOR FURTHER INFORMATION CONTACT: Sunita Shukla, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 22, Rm. 6334, Silver Spring, MD 20993-0002, 301-
796-6406, <a href="/cdn-cgi/l/email-protection#0350766d6a77622d506b76686f62436567622d6b6b702d646c75"><span class="__cf_email__" data-cfemail="4211372c2b36236c112a37292e23022426236c2a2a316c252d34">[email protected]</span></a>; or Phillip Kurs, Center for
Biologics Evaluation and Research, Food and Drug Administration, 240-
402-7911.
SUPPLEMENTARY INFORMATION:
Table of Contents
I. Background: Priority Review Voucher Program
II. Decision Not To Designate Hepatitis Delta Virus Infection
A. Background
B. ``No Significant Market in Developed Nations''
C. ``Disproportionately Affects Poor and Marginalized
Populations''
D. FDA's Determination
III. Process for Requesting Additional Diseases To Be Added to the
List
IV. Paperwork Reduction Act
V. References
I. Background: Priority Review Voucher Program
Section 524 of the FD&C Act (21 U.S.C. 360n), which was added by
section 1102 of the Food and Drug Administration Amendments Act of 2007
(Pub. L. 110-85), uses a priority review voucher (PRV) incentive to
encourage the development of new drugs, including biological products,
for prevention and treatment of certain diseases that, in the
aggregate, affect millions of people throughout the world. To be
eligible to receive a tropical disease PRV, a sponsor must submit a
human drug application that is for prevention or treatment of a
``tropical disease'' as listed under section 524(a)(3) of the FD&C Act.
This list can be expanded by the Agency under section 524(a)(3)(S) of
the FD&C Act, which authorizes FDA to designate by order ``[a]ny other
infectious disease for which there is no significant market in
developed nations and that disproportionately affects poor and
marginalized populations'' as a ``tropical disease.'' Further
information about the tropical disease PRV program can be found in the
guidance for industry ``Tropical Disease Priority Review Vouchers,''
issued on October 6, 2016 (81 FR 69537), and available at <a href="https://www.fda.gov/media/72569/download">https://www.fda.gov/media/72569/download</a>. Additions to the statutory list of
tropical diseases by an FDA final order published in the Federal
Register
[[Page 30313]]
can be accessed at <a href="https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/tropical-disease-priority-review-voucher-program">https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/tropical-disease-priority-review-voucher-program</a>.
On August 20, 2015, FDA published a final order (80 FR 50559)
(August 2015 final order) designating Chagas disease and
neurocysticercosis as additions to the list of tropical diseases under
section 524 of the FD&C Act. The August 2015 final order also set forth
FDA's interpretation of the statutory criteria for designation as a
tropical disease under section 524(a)(3)(R) of the FD&C Act
(redesignated as section 524(a)(3)(S) of the FD&C Act).
As explained in the August 2015 final order, FDA uses the World
Bank's list of ``high-income economies'' as evidence that a country
should be considered a ``developed nation'' for purposes of tropical
disease designation (Ref. 1). In the August 2015 final order, FDA
stated that it interprets the statutory criterion ``no significant
market'' (within the phrase ``no significant market in developed
nations'' under section 524(a)(3)(S) of the FD&C Act) to refer to the
market for drugs for the treatment or prevention of infectious
diseases. The August 2015 final order states, ``[b]ecause the statute
offers vouchers for applications for drugs for either the treatment or
prevention of infectious diseases, it is reasonable to assume that `no
significant market' can refer to drugs for the treatment or prevention
of infectious diseases.'' 80 FR at 50560.
In the August 2015 final order, FDA explained that it agrees with
the use of an overall flexible approach to tropical disease designation
and notes that ``[t]he purpose of section 524 of the FD&C Act is to
provide an incentive for innovation where there otherwise would be an
insufficient financial or market incentive to invest in developing
drugs for tropical diseases''. Id. To determine whether a ``significant
market'' exists in developed nations, FDA considers both the direct and
the indirect market for drugs for the treatment or prevention of a
particular infectious disease. As noted in the August 2015 final order,
the direct market reflects ``situations in which individuals (often
reimbursed by their insurers) purchase the products for use by a
specific patient,'' and ``the direct market for a drug in a developed
country can often be estimated by assessing the occurrence of a
particular disease in that country.'' 80 FR at 50560-61. Further, as
described in the August 2015 final order, FDA uses a disease prevalence
rate of 0.1 percent of the population in developed countries for aiding
in the determination of whether a significant market may exist for
treatment of a disease. In addition to disease prevalence, other
factors have been considered by FDA, including, for example, the
incidence of the disease. Incidence measures new cases that are
diagnosed in a population in a given time period. FDA also considers
whether there is a sizable indirect market for a drug for the treatment
or prevention of an infectious disease, which could be comprised of
government entities or nongovernmental organizations that wish to
purchase and distribute a drug.
As discussed below, the Agency has determined that it cannot
conclude at this time that HDV meets the statutory criteria for
designation as a ``tropical disease'' under section 524 of the FD&C
Act; thus, FDA will not add it to the list of tropical diseases for
which a human drug application may be eligible for a PRV.
II. Decision Not To Designate Hepatitis Delta Virus Infection
Based on an assessment of currently available information, FDA has
determined that HDV will not be designated as a ``tropical disease''
under section 524 of the FD&C Act.
A. Background
HDV infection, also known as ``delta hepatitis,'' is a liver
infection caused by HDV, a defective RNA virus that requires hepatitis
B virus (HBV) surface antigen (HBsAg) for replication and transmission
(Ref. 2, Ref. 3, Ref. 4). Thus, HDV infection only occurs in
individuals also infected with HBV and can be acute or chronic. Chronic
HDV/HBV infection is the most severe form of chronic viral hepatitis,
with more rapid progression to cirrhosis, hepatocellular carcinoma, and
death (Ref. 5). Cohort studies show the risk of adverse liver-related
outcomes may be 9 times higher in patients with chronic HDV/HBV
infection than in those with HBV monoinfection (Ref. 6), with greater
likelihood of liver transplantation (Ref. 7). On average, HDV/HBV
infection progresses to cirrhosis within 5 years and to hepatocellular
carcinoma within 10 years (Ref. 8).
An estimated 1.59 million persons (range 1.25-2.49 million) live
with chronic HBV infection in the United States (Ref. 9) and 254
million (range 224.0-286.6 million) globally (Ref. 10). These people
are at potential risk of HDV infection. Estimated HDV prevalence rates
reported in the literature vary widely, in part because of different
methodologies used but also because of historically low levels of HDV
testing. The presence of anti-HDV antibodies identifies HBsAg-positive
individuals who have been exposed to HDV (either in the past or due to
ongoing infection); however, detection of HDV RNA is needed to confirm
active HDV infection. Chronic HDV (CHD) infection is defined by
detectable HDV RNA in the blood for at least six months.
As noted above, HDV prevalence estimates vary widely. Some reports
suggest HDV infection may affect 12.0 million people worldwide (95% CI,
8.7-18.7) (Ref. 11, Ref. 12, Ref. 13). A meta-analysis estimated a 4.5%
(95% CI, 3.6-5.7) anti-HDV (i.e., total or IgG anti-HDV antibodies)
prevalence rate among HBsAg-positive persons and 16.4% (95% CI, 14.6-
18.6) among those attending hepatology clinics (Ref. 13). Other meta-
analyses estimated 13.0% (95% CI, 12.0-14.1) HDV infection prevalence
among HBV carriers and 0.80% (95% CI, 0.6-1.0) in the general
population, corresponding to 48-60 million HDV infections globally
(Ref. 8).
Higher HDV rates are observed in low- and middle-income countries,
with highest rates reported in Mongolia, Brazil, the Republic of
Moldova, and countries in Western and Middle Africa (Ref. 14, Ref. 13).
Higher rates are also reported in people who inject drugs (PWID),
hemodialysis recipients, men who have sex with men, commercial sex
workers, and those living with hepatitis C virus (HCV) or human
immunodeficiency virus (HIV) (Ref. 15, Ref. 13, Ref. 16). In high-
income countries, a substantial proportion of HDV infections are found
in immigrant populations (Ref. 17, Ref. 18). For example, foreign-born
persons were reported to contribute more than 50% of the HDV infection
burden in both Greece and Germany (Ref. 17). An Italian study reported
that while the rate of anti-HDV antibody positivity in Italy had
declined among native-born Italians, there was a 6-fold increase among
people born abroad (Ref. 19). Meanwhile, in a study of chronic viral
hepatitis infections among people of Mongolian descent in Southern
California, all but three of whom were foreign-born, the anti-HDV
antibody prevalence rate was 39.6% and HDV RNA positivity was 34.0%
among those with chronic HBV infection, rates that are as high as those
reported in Mongolia (Ref. 20).
Given the dependence of HDV on HBV for its propagation, the most
effective means of HDV prevention is HBV vaccination. Hepatitis B
immunization, however, does not protect against HDV in those already
chronically infected with HBV. By 2024, global coverage of three infant
doses of the hepatitis B vaccine reached 84%
[[Page 30314]]
(Ref. 21, Ref. 22). In the United States, adult HBV vaccination
coverage was reported as 30-33% (Ref. 23 (discussing the standard
recommended 3-dose vaccine coverage), Ref. 24 (discussing having
received at least one vaccine dose)).\1\ In response, in 2022, the
Advisory Committee on Immunization Practices (ACIP) recommended
universal hepatitis B vaccination for all U.S. adults aged 19 through
59 years (Ref. 25), in contrast to previous recommendations that were
risk-factor based. As of March 2026, the Centers for Disease Control
and Prevention (CDC) continues to recommend universal HBV vaccination
for all adults aged 19 through 59 years, with shared clinical decision-
making for adults aged 60 years or older (Ref. 26).
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\1\ The U.S. Census Bureau reports the total population in the
United States per the 2020 Decennial Census is 331,449, 281 (see
Ref. 49), and estimates the total population in the United States as
of July 1, 2025 to be 341,784,857 (see Ref. 50). Additionally, the
U.S. Census Bureau estimates that 21.5% of the U.S. population is
under 18 years of age, and that 14.1% of the U.S. population between
2020-2024 are foreign-born persons (see Ref. 50).
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Therapeutic options for CHD are limited. Nucleos(t)ide analogues,
such as tenofovir disoproxil fumarate, entecavir, and tenofovir
alafenamide, are first-line HBV treatments but ineffective against HDV,
either alone or in combination with pegylated interferon-[alpha] (Peg-
IFN[alpha]) (Ref. 27, Ref. 28, Ref. 29).
In the United States, there is no FDA-approved treatment for CHD.
Pegylated interferon-[alpha] has been endorsed by some treatment
guidelines (Ref. 27, Ref. 30), but many HDV patients are ineligible due
to advanced liver disease or contraindications. In addition, Peg-
IFN[alpha] therapy causes adverse side effects, such as flu-like
symptoms, anemia, neutropenia, and thrombocytopenia, resulting in poor
tolerability and high discontinuation rates (Ref. 31). Moreover,
response rates are variable, ranging from 17% to 35%, and relapses are
common (Ref. 32, Ref. 33, Ref. 5). Outside the United States,
bulevirtide (Hepcludex[supreg] in the European Economic Area [EEA],
United Kingdom [UK], Switzerland, and Australia; Myrcludex B[supreg] in
Russia) is approved for CHD treatment in adults with compensated liver
disease. To date, FDA has not approved bulevirtide for treatment of
CHD.
B. No Significant Market in Developed Nations
It cannot be concluded that there is no significant market in
developed nations for drugs to treat or prevent HDV infection.
As noted above, FDA is authorized to designate certain diseases as
tropical diseases if certain criteria are met. The first criterion is
that ``there is no significant market in developed nations.'' As stated
in the August 2015 final order, FDA intends to use a country's presence
on the World Bank list of ``high income economies'' as evidence that
the country should be considered a ``developed nation'' for ``tropical
disease'' determination purposes (80 FR at 50560).
In the August 2015 final order, FDA further explains that it agrees
with the use of an overall flexible approach to tropical disease
designation and notes that ``[t]he purpose of section 524 of the FD&C
Act is to provide an incentive for innovation where there otherwise
would be an insufficient financial or market incentive to invest in
developing drugs for tropical diseases''. Id. FDA explains that it
``will analyze the market for drugs for both the treatment and
prevention of infectious diseases.'' Id. FDA further identifies factors
to consider in determining whether a ``significant market'' exists in
developed countries. First, FDA explains that there are ``direct''
markets--that is, markets in which patients purchase drugs for their
own use. Id. In discussing the direct market, FDA identifies one
relevant factor, disease prevalence, explaining that ``if the
prevalence of a disease in developed countries is less than 0.1 percent
of the population of those countries, it is unlikely that ordinary
market forces will offer a sufficient incentive to drive the
development of new preventions or treatments.'' Id. at 50561. Other
factors have been considered by FDA, including, for example, the
incidence of the disease. See 85 FR 42860 (July 15, 2020) (designating
brucellosis); 85 FR 42871 (July 15, 2020) (declining to designate
coccidioidomycosis); 80 FR 50559 (Aug. 20, 2015) (designating
neurocysticercosis); and 83 FR 42904 (Aug. 24, 2018) (designating
rabies). Second, FDA states in the August 2015 final order that ``some
drugs may have a sizeable `indirect market' composed of, for example,
government entities or nongovernmental organizations that wish to
purchase and distribute a drug for the treatment or prevention of an
infectious disease, which could be relevant to the analysis, as well.
Id.
The literature suggests that HDV infection prevalence is higher
among low- and lower-middle-income countries compared to high-income
countries, and disproportionately affects countries in regions such as
Africa, Central and South Asia, and Oceania that are included in the
World Bank list of low-income economies (Ref. 15, Ref. 13). Gilead
provided Table 1 below to show prevalence rates of HDV infection among
8 countries included on the World Bank list of high-income economies
(Ref. 52).
Table 1--Summary of Percent HDV Infection Prevalence in the General Population in High Income Economies
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(%) Prevalence in
High-income economies general population * (95% CI)
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Australia.................................... 0.01 (0.0, 0.02).
France....................................... 0.01 (0.004, 0.01).
Germany...................................... 0.02 (0.01, 0.03).
Italy........................................ 0.02 (0, 0.1).
Japan........................................ 0.70 (0.5, 0.9).
Saudi Arabia................................. 0.10 (0.01, 0.2).
United Kingdom............................... 0.02 (0.001, 0.1).
United States................................ 0.02 (0.01, 0.03).
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Source: Gilead's Tropical Disease Designation Request (Ref. 52, based on Ref. 13).
* Prevalence represents the country-level anti-HDV prevalence in the total population.
Of note, Gilead purports that the higher HDV infection prevalence
rate in Japan (0.70%) is likely an over-estimation given that the
limited data obtained from two small studies in a remote region of
Japan are likely not
[[Page 30315]]
representative of the overall population. The basis for this assertion,
however, is unclear.
It is notable that there are additional countries on the World Bank
list of high-income economies not included in the above table (many of
which do not have published HDV prevalence rates). For instance,
Romania is a high-income country and has an HDV prevalence in the
general population of 0.4% (95% CI, 0.1-1.5) (Ref. 13).
Published literature also indicates that the estimated prevalence
of HDV infection in the United States is possibly higher than reported
by Gilead in Table 1. Determining U.S. HDV prevalence is challenging
for several reasons. First, HDV screening is not routine and testing
rates among chronic HBV patients are suboptimal. For example, a
Veterans Affairs study found that less than 8% of HBsAg-positive
patients had been tested for HDV (Ref. 34). Second, HDV infection is
not a nationally notifiable condition, so the actual number of U.S.
cases is unknown according to the CDC (Ref. 35). A 2019 review found
anti-HDV antibody positivity among U.S. HBsAg-positive carriers ranged
from 2% to 50%, depending on the population sampled (Ref. 36).
Reference 13, which is relied on by Gilead in Table 1, above,
acknowledges limited North America data and variable U.S. HDV
prevalence estimates.
A National Health and Nutrition Examination Survey (NHANES) study,
using data from 2011 through 2016, reported anti-HDV antibody
prevalence of 0.11% (95% CI, 0.08-0.17) in the overall U.S. population
aged >= 6 years and 0.15% (95% CI (0.10-0.23) among adults aged >= 18
years (Ref. 37). These rates are markedly higher than those noted by
Gilead in Table 1 (Ref. 13). It is also worth noting that NHANES data
may underrepresent foreign-born persons (Ref. 38), who drive HDV
prevalence in developed nations including the United States, suggesting
that actual U.S. prevalence may be higher.
More recent publications continue to report varying HDV prevalence
in the United States and other high-income countries, though these too
may underestimate true prevalence due to limited clinical recognition
of HDV and testing. A study using an All-Payer Claims Database
estimated 4.6% HDV prevalence among HBV patients in the United States
from 2015 to 2019 (Ref. 39). A retrospective study of three U.S. urban
safety-net health systems from 2010 to 2022 found that 15.7% of tested
chronic HBV patients were anti-HDV antibody positive, though only 6.1%
of chronic HBV patients were tested for HDV, and among those tested,
only two patients (1.6%) received follow-up HDV RNA testing (Ref. 40).
A literature review and meta-analysis using 2022 U.S. Census Bureau
data estimated a weighted average HDV prevalence of 4.2% among foreign-
born persons with chronic HBV infection (64,938 persons [95% CI 33,055-
97,392]), and a total of 1.97 million (95% CI 1.547-2.508) persons
living with chronic HBV and 75,005 (95% CI 42,187-108,393) persons
living with HDV in the United States in 2022 (Ref. 41). In Canada, a
similar analysis using 2021 Statistics Canada data estimated the
weighted average HDV prevalence among foreign-born persons with chronic
HBV infection at 5.19% (17,848 persons [95% CI 9,611-26,052]), with an
estimated 0.55 million (95% CI 0.488-0.615) persons living with chronic
HBV and 35,059 (95% CI 18,744-52,083) persons living with HDV in 2021
(Ref. 42).\2\ In Italy, a 2024 study estimated HDV prevalence at 7.7%
among adults with chronic HBV infection and 0.019% in the general
population (Ref. 43).
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\2\ The Government of Canada reports the total population of
Canada per the 2021 census data to be 36,991,981 (see Ref. 51).
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The available HDV prevalence data have significant limitations,
chief among them is the undertesting of chronic HBV patients for HDV.
In addition, methodological differences across published studies, the
use of estimated rates with wide variability, and reliance on anti-HDV
antibody data with a lack of HDV RNA data can all potentially result in
over- or under-estimation of true HDV prevalence. Given the data
discussed above, these limitations, and the reported variability, in
several high-income economies, it cannot be concluded that HDV
prevalence is less than 0.1%.
Beyond prevalence data, evidence exists for a direct market for HDV
drugs. Notably, bulevirtide is approved as Hepcludex[supreg] in the
EEA, UK, Switzerland, and Australia, and as Myrcludex B[supreg] in
Russia, for the treatment of CHD in adults with compensated liver
disease. Bulevirtide received conditional Marketing Authorization (MA)
from the European Commission in July 2020 and converted to full MA in
July 2023. The UK conditional MA converted to full MA in August 2023,
and Switzerland granted full MA in February 2024 (Ref. 44).
Available bulevirtide sales data are limited. Early reports from
Gilead noted bulevirtide contributed $7 million in Q2 2021 following
initial European approval in July 2020 (Ref. 45). According to Gilead's
Fourth Quarter and Full Year 2025 Financial Results, ``The Liver
Disease portfolio sales increased 6% to $3.2 billion in the full year
2025 compared to 2024, primarily driven by higher demand for Livdelzi
and products for chronic hepatitis B virus (``HBV'') and chronic
hepatitis delta virus (``HDV''), partially offset by lower average
realized price in products for chronic hepatitis C virus (``HCV'')''
(Ref. 46). Hepcludex[supreg] (bulevirtide) sales are not reported
separately, making it difficult to determine its specific contribution.
Additionally, according to <a href="http://clinicaltrials.gov">clinicaltrials.gov</a>, there are several
investigational agents for the treatment of chronic HDV that have
ongoing or completed Phase 3 trials, including pegylated interferon
lambda-1a, lonafarnib/ritonavir, tobevibart plus elebsiran, brelovitug,
and hepalatide.
A preventive product developed specifically for HDV infection would
likely find a direct market given the estimated 1.59 million persons
(range 1.25-2.49 million) living with chronic HBV infection in the
United States (Ref. 9) and 254 million (range 224.0--286.6 million)
globally (Ref. 10). Patel et al. estimated HBsAg prevalence of 0.36%
(95% CI 0.29-0.46) among U.S. adults aged >=18 years, indicating a
sizeable patient population with chronic HBV infection that could
benefit from measures to prevent HDV superinfection (when a person with
chronic HBV infection becomes newly infected with HDV) (Ref. 37).
Regarding an indirect market, HDV is not on the CDC list of
potential bioterrorism agents. Gilead states they are unaware of any
significant U.S. government funding for HDV drug development.
Consistent with this, the Viral Hepatitis National Strategic Plan 2021-
2025 focuses only on hepatitis A, B, and C (Ref. 47). Thus, no apparent
``indirect'' market exists for HDV treatment or prevention within the
United States.
In summary, literature evidence suggests HDV prevalence exceeds
0.1% in several high-income countries, including Japan, Romania, Saudi
Arabia, and possibly the United States, though variability exists in
reported rates, likely due to inconsistent and suboptimal HDV testing.
Other evidence for a direct treatment market includes bulevirtide's
approval in several developed nations and Phase 3 clinical trials of
investigational agents listed on <a href="http://clinicaltrials.gov">clinicaltrials.gov</a>. Evidence for a
direct prevention market includes consistently reported chronic HBV
infection rates well above 0.1% in the United States. Although
hepatitis B vaccination prevents both HBV and HDV infection,
[[Page 30316]]
HBV vaccine coverage remains underutilized in the United States.
Because patients with chronic HBV infection are at risk for HDV
superinfection, a preventative product for this patient population
would find a sizeable market if developed. Although no apparent
indirect market exists for HDV treatments or preventions within the
United States, this does not outweigh the direct market evidence.
Therefore, it cannot be concluded that no significant market exists in
developed nations for treatment or prevention of HDV infection.
C. Disproportionately Affects Poor and Marginalized Populations
The relative burden of HDV infection has been reported to be
greatest amongst impoverished and marginalized populations. In a
systematic review and meta-analysis, Chen et al. summarized the
association between sociodemographic development index (SDI), a
composite indicator of development status correlated with health
outcome, and HDV prevalence from 61 countries and found that immigrant
populations from countries with low SDI were associated with higher HDV
prevalence (Ref. 17). Further, disproportionately higher rates of HDV
persist in other marginalized populations, such as in PWID, people
living with HIV or HCV, and people with high-risk sexual behaviors
(Ref. 15, Ref. 13, Ref. 16).
While HDV infection has not been designated by the WHO as a
neglected tropical disease, a panel of scientists and public health
experts from academia and the WHO published a study in the Journal of
Hepatology in 2020 (Ref. 13, Ref. 48) highlighting the need to improve
the response to HDV. When discussing this study, one of the co-authors
stated that ``HDV has long been neglected, because for decades the
prevalence of infection remained uncertain and effective treatment was
lacking.'' (Ref. 48).
D. FDA's Determination
In conclusion, based on the totality of available data, HDV
infection does not currently meet the statutory criteria to be
designated by order as a tropical disease under section 524 of the FD&C
Act. While HDV infection ``disproportionately affects poor and
marginalized populations,'' it cannot be concluded that ``there is no
significant market in developed nations'' for treatment and prevention
of HDV infection.
III. Process for Requesting Additional Diseases To Be Added to the List
FDA's current determination regarding HDV infection does not
preclude interested persons from requesting its consideration in the
future as additional new data become available. To facilitate the
consideration of future additions to the list, FDA established a public
docket (see <a href="https://www.regulations.gov">https://www.regulations.gov</a>, Docket No. FDA-2008-N-0567)
through which interested persons may submit requests for additional
diseases to be added to the list. Such requests should be accompanied
by information to document that the disease meets the criteria set
forth in section 524(a)(3)(S) of the FD&C Act. FDA will periodically
review these requests, and, when appropriate, expand the list. For
further information, see FDA's Tropical Disease Priority Review Voucher
Program web page at <a href="https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/tropical-disease-priority-review-voucher-program">https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/tropical-disease-priority-review-voucher-program</a>.
IV. Paperwork Reduction Act
This notice reiterates the ``open'' status of the previously
established public docket through which interested persons may submit
requests for additional diseases to be added to the list of tropical
diseases that FDA has found to meet the criteria in section
524(a)(3)(S) of the FD&C Act. Such a request for information is exempt
from Office of Management and Budget review under 5 CFR 1320.3(h)(4) of
the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3521).
Specifically, ``[f]acts or opinions submitted in response to general
solicitations of comments from the public, published in the Federal
Register or other publications, regardless of the form or format
thereof'' are exempt, ``provided that no person is required to supply
specific information pertaining to the commenter, other than that
necessary for self-identification, as a condition of the full
consideration of the comment.''
V. References
The following references marked with an asterisk (*) are on display
at the Dockets Management Staff (see ADDRESSES) and are available for
viewing by interested persons between 9 a.m. and 4 p.m., Monday through
Friday; they also are available electronically at <a href="https://www.regulations.gov">https://www.regulations.gov</a>. References without asterisks are not on public
display at <a href="https://www.regulations.gov">https://www.regulations.gov</a> because they have copyright
restriction. Some may be available at the website address, if listed.
References without asterisks are available for viewing only at the
Dockets Management Staff. FDA has verified the website addresses, as of
the date this document publishes in the Federal Register,but websites
are subject to change over time.
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20. Fong TL, Lee BT, Chang M, Nasanbayar K, Tsogtoo E, Boldbaatar D,
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25. Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B
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27. European Association for the Study of the Liver (EASL). EASL
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28. Wedemeyer H, Yurdaydin C, Hardtke S, Caruntu FA, Curescu MG,
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[[Page 30318]]
2026).
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-10268 Filed 5-21-26; 8:45 am]
BILLING CODE 4164-01-P
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