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Disorders
of the Blood
More Than 500 Medicines in Development for Blood and
Bleeding Disorders, Including Blood Cancers
Blood helps the human body perform functions vital to staying alive. Red blood cells deliver oxygen to the tissues while white
blood cells fight infection and platelets help blood clot. Any disruption to these activities can pose a serious health threat.
Disorders of the blood can include problems with blood cells, platelets, blood vessels, bone marrow, lymph nodes, the spleen and
proteins involved in bleeding and clotting. Blood disorders can have genetic causes, while others can develop as a result of other
diseases, side effects from other therapies or lack of certain nutrients in the diet.

There are many different types of blood disorders. For example, blood disorders that affect the red blood cells can lead
to hemophilia, blood clots and anemia, while disorders that affect the white blood cells may lead to blood cancer, such as
leukemia, lymphoma and myeloma.

Patients with blood disorders, including bleeding disorders, can often face tremendous burden in treating and managing their
conditions, and often require lifelong treatment, involving routine drug infusions or blood transfusions to manage the condition
and help prevent serious complications. Patients with these disorders often experience debilitating pain, disability, reduced life
expectancy and quality of life.

An estimated More than

JUST THE
FACTS
184,000 3.2 million
Americans will be diagnosed with a Americans are living with
blood cancer in 20221 a bleeding disorder2

About More than

100,000 3 million
Americans have Americans have
sickle cell disease3 a form of anemia4
Blood cancers account for nearly 10% of all new cancer diagnoses1 and include leukemia, lymphoma, hematological
malignancies, myelodysplastic syndromes, myeloma and myeloproliferative neoplasms. In recent years, science has advanced
quickly and allowed for more precise treatments as our understanding of blood cancers and ability to treat them grows.

This report on medicines in development for blood disorders includes a broad range of diseases with different origins, symptoms
and treatments. To address the varying need for new treatments, America’s biopharmaceutical research companies are currently
developing 549 medicines targeting blood disorders.5 These medicines are either in clinical trials or under review by the U.S. Food
and Drug Administration (FDA) and include:

• 162 for lymphoma, which account for nearly 5% of all new cancer diagnoses. Non-Hodgkin lymphoma accounts for 90% of
all lymphomas.1

• 158 for several types of leukemia, which account for more than 3% of all new cases of cancer. The most common types of
leukemia in American adults are chronic lymphocytic leukemia (38%) and acute myeloid leukemia (31%). In children and
adolescents, 75% of leukemia cases are acute lymphoblastic leukemia.1

• 84 for multiple myeloma, with an estimated 34,470 new cases and 12,640 deaths expected in 2022.1

• 73 for hematologic malignancies, cancer that caused by the uncontrolled division of abnormal cells and can lead to
leukemia, lymphoma and multiple myeloma.

• 55 for myelodysplastic syndromes, a group of conditions that happen when the blood-forming cells in the bone marrow
become abnormal leading to a low number of blood cells.

• 30 for myeloproliferative disorders, such myelofibrosis, essential thrombocytopenia and polycythemia vera.

• 30 for sickle cell disease, a red blood cell disorder that causes normal round, flexible cells to form into a crescent or sickle
shape. These malformed blood cells clog blood vessels preventing normal flow of nutrition and oxygen throughout the
body, causing pain, organ damage and a low blood cell count.

• 23 for various forms of anemia, which affect more than 3 million Americans and collectively are the most common bleeding
disorder in the U.S.4/6

• 19 for platelet disorders, including thrombocytopenia, a disease characterized by an excess of platelets.

• 18 for hemophilia, a genetic disorder classified as type A is caused by a factor VIII deficiency, while type B is caused by a
factor IX deficiency. Between 30,000-33,000 people in the U.S. have a form of hemophilia.2

• 14 for clotting disorders, consisting principally of deep vein thrombosis, where a blood clot is located in the deep veins
or the arms or legs, and pulmonary embolism, where a clot has traveled from a deep vein to the lung. About 100,000
Americans die each year from blood clots.3

• 13 for paroxysmal nocturnal hemoglobinuria, a rare disease of the blood characterized by the destruction of red blood cells,
blood clots and impaired bone marrow function.

• 9 for thalassemia, an inherited blood disorder where the blood doesn’t make enough hemoglobin leading to red blood cells
that don’t function correctly and only last a short time.3

• 16 for other blood disorders, such as erythropoietic protoporphyria (an inherited condition that can cause pain when
patients are exposed to light), hemorrhage and retinal vein occlusion (blood clots in the eye veins), among others.

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 Medicines in Development for Disorders of the Blood
Anemia 22

Blood Clots 18

Hematologic Malignancies 56

Hemophilia 18
Leukemia 159

Lymphoma 173

Multiple Myeloma 82

Myelodysplastic Syndromes 57

Myeloproliferative Disorders 32

Paroxysmal Nocturnal Hemoglobinuria 11

Sickle Cell Disease 30 * Some medicines may

be in more than one
Thalassemia 9 category.
Thrombocytopenia 15 PHASE I
PHASE II
Others 17
PHASE III
0 20 40 60 80 100 120 140 160 180 200 APPLICATION SUBMITTED

Innovative Medicines in the Blood Disorder Pipeline

Among the 549 medicines in development for blood disorders are treatments that employ scientific and technical knowledge
in new ways or expand on current knowledge. Many of the medicines represent innovative new ways to target a blood disorder,
including:

 bio-engineered adeno-associated virus (AAV) vector-based gene therapy is being developed to treat hemophilia A, or
•A
factor VIII deficiency. Hemophilia is a rare, serious inherited bleeding disorder, characterized by mutations in the F8 gene.
The mutation leads to deficient blood coagulation and an increased risk of bleeding or hemorrhaging.

• A gene therapy is in development that uses AAV vectors to deliver a high-activity Factor IX gene to the liver for the
treatment of hemophilia B. Hemophilia B is caused by a mutation in Factor IX, which leads to deficient blood coagulation
and an increased risk of bleeding or hemorrhaging. Hemophilia B is four times less common than hemophilia A.2

• A potential first-in-class medicine is in development for the treatment of paroxysmal nocturnal hemoglobinuria (PNH),
a rare hematopoietic stem cell disorder (affecting .05-1.5 per million people worldwide)7 where red blood cells become
defective and subsequently produce defective red blood cells. These defective red blood cells in PNH are highly susceptible
to premature destruction by a part of the body’s own immune system called the complement system. The medicine,
a complement factor B inhibitor, targets the underlying cause of PNH through its action on the complement system’s
alternative pathway.

• A therapy in development for hereditary thrombotic thrombocytopenic purpura (hTTP) is a bio-engineered version of the
naturally occurring protein ADAMTS13 that plays a critical role in blood coagulation. A deficiency of the protein can lead
to the formation of blood clots in the small blood vessels throughout the body, leading to TTP. Acquired TTP is often due
to antibodies directed against ADAMTS13, while hTTP is caused by mutations of the ADAMTS13 gene, resulting in a severe
deficiency of the protein. The therapy is also being studied as a treatment of vaso-crisis related to sickle cell disease. About
4,000 people have hTTP worldwide.

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Recent Advances in Treatment for Blood Disorders
While there is still significant unmet need for patients with certain blood disorders, progress has been made in treating and
reducing the burden of disease for many patients. In the first three months of 2022 alone, three new treatments have been
approved by the FDA for varying disorders. Some recent medicine approvals provide treatment options for patients where there
were few or none previously available include:

• The first disease-modifying therapy for hemolytic anemia in adults with pyruvate kinase deficiency, a rare, inherited life-
long debilitating anemia. An inherited mutation in the PKLR gene can cause a deficit in energy within the red blood cell.

• Three new CAR-T cell therapies, two for the treatment of relapsed or refractory multiple myeloma and one for large B-cell
lymphoma.

• The first approved treatment for cytopenic myelofibrosis, a rare form of bone marrow cancer. Cytopenic myelofibrosis
is a severe form of the disease with thrombocytopenia (very low blood platelet counts). About two-thirds of patients with
myelofibrosis suffer from cytopenias.

• An approved medicine for the treatment of von Willebrand disease was recently approved for the prevention of bleeding
episodes in a severe form of the disease in adults. The treatment is a recombinant von Willebrand factor replacement
therapy.

• The first targeted biologic to reduce pain crises (vaso-occlusion) in sickle cell disease. The medicine binds a protein that
plays a key role in the interactions at the cellular level that can lead to pain crises in people with the sickle cell disease.
Pain crises are the most common cause of hospitalizations in people with sickle cell disease, leading to approximately
200,000 ER visits each year in the US.

• The first approved medicine that directly targets the root cause of the sickling and destruction of the red blood cells
in sickle cell disease. The medicine works by increasing hemoglobin’s affinity for oxygen, which in turn inhibits sickle
hemoglobin polymerization – a central abnormality in sickle cell disease.

Disparities in Blood Disorders

Blood disorders vary in prevalence and death rates between ages, sex, racial and ethnic groups. For instance, while men have a
higher risk for blood clots (thrombosis), women have risks men do not, such as higher estrogen levels, a key ingredient in birth
control regimens and postmenopausal hormone therapy.8

Many bleeding disorders are genetic or inherited, affecting children at higher rates. For example, sickle cell disease
disproportionately affects Black and Hispanic children with an incidence rate of 73.1 cases per 1,000 Black newborns carrying
the sickle cell trait and 6.9 cases per 1,000 Hispanic newborns, compared to 3 cases per 1,000 births for white newborns.3
People with Fanconi anemia, the most common inherited form of aplastic anemia, are born with the disorder, but symptoms may
not be apparent at birth. Most people are diagnosed with the disorder between ages 3-14.9

Myeloma is most often diagnosed in people age 65 and older. African-Americans are twice as
likely to be diagnosed with myeloma than white Americans and at a younger age.10

During pregnancy, the amount of blood in a women’s body increases by 20-30%, which increases
the amount of iron and vitamins the body needs to make hemoglobin. Many women experience
anemia due to a lack of iron during pregnancy, especially during the 2nd and 3rd trimesters.6

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Blood Disorders and Rare Diseases
In the U.S., as many as 30 million people have a rare disease – a disease or condition that affects fewer than 200,000 people
– and about 80% of rare diseases are genetic in origin with the vast majority – about 50% – impacting children.11 Not all rare
diseases are blood disorders, but many are. Rare blood disorders can impact significantly smaller groups of patients, sometimes
as small as a few hundred or even less.

Examples of some rare diseases that affect the blood are aplastic anemia with fewer than 1,000 people diagnosed each year in
the U.S.,12 myelofibrosis with less than 20,000 people living with the disease in the U.S.12 and hairy cell leukemia affecting about
6,000 Americans.7 Several rare bleeding disorders can occur with just a few cases in 1-2 million people, such as Waldenstrom
macroglobulinemia,1 inherited platelet diseases and disorders due to blood factor deficiencies.2

For people with a rare blood disorder, as with many rare diseases, simply getting a diagnosis can be a complicated, lengthy
and frustrating journey, particularly for patients in underserved communities and others lacking ready access to health care.
Inadequate diagnostic tools and limited awareness of rare blood disorders along with limited available treatment options for
many rare diseases make it difficult to identify and diagnose rare blood disorders. On average, it can take more than seven
years, and an often-burdensome process, for a rare disease patient to receive an accurate diagnosis.11

America’s biopharmaceutical companies are leveraging new technologies and expanding scientific understanding of the genetic
basis of many rare blood disorders to develop groundbreaking therapies for them. Advances in personalized medicine and cell
and gene therapies are among some of the innovative approaches that are creating new opportunities to advance research into
rare blood disorders and the development of new treatments. But the development of new and effective treatments also face
many challenges, such as delayed diagnosis or misdiagnosis, limited scientific and medical knowledge about the disorder and
small patient populations.

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Gene Therapy and Bleeding Disorders 13

Because many blood disorders are caused by genetic abnormalities, gene

Success in Treating
therapies in development hold tremendous promise in offering long-term Blood Cancers
benefits, or in some cases a cure for patients with these conditions. As a
result, they offer to dramatically reduce existing treatment burden and costs. A range of game-changing new
approaches to blood cancer treatment
Hemophilia A have become available to patients with
The standard of care for many hemophilia A patients, particularly those a wide range of cancers over the past
with more severe disease, includes lifelong treatment with factor (FVIII) decade, contributing greatly to significant
replacement therapy administered up to 2-3 times a week, or 100-150 times a reductions in mortality and increases
year, to prevent dangerous bleeding events and preserve joint function. More in survival. Many of these significant
recently, a new type of prophylactic therapy has also become available which advancements are due to advancements
may be self-administered less frequently. Gene therapies in the late stages in CAR-T therapy. CAR-T is a form of gene
of development for severe hemophilia A have shown evidence of significant modified cell therapy which permanently
and sustained reductions in bleeding rates as well as an almost complete alters the “genetic instructions” of a
reduction in factor replacement therapy utilization in the years following a patient’s T-cells to recognize, target and kill
one-time administration of therapy. cancer cells.
Hemophilia B
Like hemophilia A, hemophilia B patients often require life-long prophylactic To make the treatment, T-cells are
infusions of factor replacement therapy to replace or supplement low levels separated from blood taken from a patient
of IX blood-clotting factor and to prevent life-threatening bleeding events and genetically engineered to produce
and to reduce joint bleeding events and preserve joint function. Infusions specialized receptors on their cell surface.
are generally administered 2-3 times a week, or 100-150 times a year. These receptors, called chimeric antigen
Though some newer factor replacement therapy products offer to extend the receptors (CAR), provide T-cells with the
frequency of infusion to once every 1-2 weeks. capability to recognize and attack tumor
cells with specific proteins called antigens
Gene therapies in the late stages of development for severe and moderately on their surfaces. These potent CAR-T cells
severe hemophilia B have shown evidence of significant and sustained are modified and duplicated outside the
reductions in bleeding rates as well as an almost complete reduction in body and infused into the patient, where
factor replacement therapy utilization in the years following a one-time they recognize and kill cancer cells.
administration of therapy.
Currently, there are six FDA approved
Sickle Cell Disease
CAR-T therapies to treat blood cancers,
Sickle cell disease is an inherited red blood cell disorder that leads to
including multiple myeloma, mantle-cell
abnormal hemoglobin, the protein that delivers oxygen throughout the body.
lymphoma, large B-cell lymphoma, acute
It is an extremely painful and dangerous condition. When “sickle” shaped red
lymphoblastic leukemia, diffuse large
blood cells become stuck in blood vessels, they can lead to pain crisis, known
B-cell lymphoma and follicular lymphoma.
as vaso-occlusive crisis, and if they prevent the flow of oxygen to the chest,
These therapies have demonstrated
they can cause a serious complication known as acute chest syndrome.
unprecedented remission rates as
Blocked flow of oxygen to the brain can also lead to stroke. Though chronic
high as 93%14 and many are having a
red blood cell transfusions and medications may help to prevent these serious
transformative impact in certain cancers.
and life-threatening complications, patients with sickle cell disease experience
For example, several CAR-T cell therapies
frequent hospitalizations. For example, sickle cell disease patients on average
have shown to cure some children and
are hospitalized more than once a year for significant pain, with an average
adolescents with advanced leukemia,
length of stay of 5 days. Additionally, on average patients visit the emergency
sparing the short and long-term side
room two to three times a year, most commonly due to pain crisis.
effects of previous treatments.

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A potential gene therapy in the late stages of development has shown evidence in clinical trials of an almost complete reduction
in painful vaso-occlusive crisis and acute chest syndrome in the years following a one-time administration of therapy.

Beta Thalassemia
Beta thalassemia impacts red blood cells by reducing the production of oxygen-carrying hemoglobin, resulting in a lack of
oxygen carried to many parts of the body. Patients with severe beta thalassemia and debilitating anemia may be eligible to
receive a curative stem cell transplant. But few can find suitable donors and even less — approximately 10% — ultimately receive
a stem cell transplant. Instead, most severe patients are treated through a regimen of lifelong blood transfusions to maintain
levels of functional hemoglobin. On average, patients in the U.S. will require 17 transfusions a year, lasting multiple hours per
procedure. These transfusions can also lead to various side effects, the most notable of which is iron overload. To counter iron
overload, patients often need iron chelator therapies to manage the disease. Unfortunately, many patients with severe beta
thalassemia often die from cardiac complications of iron overload by 30 years of age.

A gene therapy in the late stages of development for transfusion dependent adults and children with beta thalassemia has
shown evidence in clinical trials of the potential to eliminate dependence on regular blood transfusions and medicines to
manage side effects of treatment in the years following a one-time administration of therapy.

Facts for Selected Blood Disorders

Anemia Blood Clots Hemophilia

More than 3 million Americans As many as 900,000 American A genetic disorder that is more
affected by anemia1 and 5,633 experience a blood clot (venous common in males than females.
people died from a form of anemia2 thrombosis) and about 100,000 people Hemophilia A is 4X as common as
will die each year2 hemophilia B. As many as 33,000
people have hemophilia in the US2

Leukemia Lymphoma Myelodysplastic Syndrome

It is estimated that 60,650 Americans It is estimated that 89,010 Americans will A group of conditions where cells
will be diagnosed with a form of be diagnosed with a form of lymphoma in in the bone marrow are abnormal.
leukemia in 2022 (35,810 males, 2022 (48,690 males, 40,320 females) and In 2020, 6,881 Americans died2
24,840 females) and 24,000 will die 21,170 will die (12,250 males, 8,920 females)3 from the disease and an estimated
(14,020 males, 9,980 females)3 10,000 live with the disease3

Myeloma Sickle Cell Disease Von Willebrand Disease

It is estimated that 34,470 An inherited disorder affects about 100,000 The most common bleeding
Americans will be diagnosed with Americans and is more common in Black disorder affects about 1 in
myeloma in 2022 (19,100 males, Americans. About 1 out of every 365 Black every 100 people.2
15,370 females) and 12,640 will die newborns have the disease and 1 in 13 have the
(7,090 males, 5,550 females)3 sickle cell trait.2

Sources: 1. National Heart Lung and Blood Institute, 2. Centers for Disease Control and Prevention, 3. American Cancer Society

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Sources:

1. American Cancer Society, 22 Cancer Facts & Figures

2. National Hemophilia Foundation
3. U.S. Centers for Disease Control and Prevention (CDC)
4. National Heart, Lung and Blood Institute, National Institutes of Health
5. Number of medicines obtained through public, government and industry sources, and the Adis “R&D Insight” database; current as of May 5, 2022.
6. American Society of Hematology
7. National Organization for Rare Disorders
8. American Society of Hematology, Women and the Risk of Blood Clots
9. National Library of Medicine, Medline Plus, www.medlineplus.gov/ency/article/000334.htm
10. National Cancer Institute, Multiple Myeloma Awareness and African American Disparities
11. Global Genes, www.globalgenes.org
12. Health Grades, www.healthgrades.com/right-care/blood-conditions/7-rare-diseases-that-affect-the-blood
13.PhRMA, Potential Gene Therapies Hold Promise for Transforming the Trajectory of Many Blood Disorders and in Reducing Significant Treatment
Burden and Costs
14. Labiotech UG, www.labiotech.eu/in-depth/car-t-therapy-cancer-review/

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