Pipeline

Fedratinib

Myeloproliferative Neoplasms (MPN) are characterized by the mutations of JAK2, MPL or CALR. As shown in the figure, the mutational activation of JAK2 is the primary MPN disease driver.

Equipped with this knowledge and supporting clinical studies, we are developing fedratinib, a potent and targeted oral small molecule JAK2 kinase inhibitor for the treatment of myelofibrosis (MF) and polycythemia vera (PV).

Beyond MPNs, fedratinib has potential applications in the treatment of acute myeloid leukemia (AML) and colorectal cancer (CRC).

Sanofi completed a Phase 3 placebo-controlled trial with fedratinib for the first-line treatment of myelofibrosis. A total of 288 subjects were randomized to receive 400mg or 500mg daily of fedratinib or placebo. Fedratinib achieved its primary endpoint, a >35% reduction in spleen size at week 24 (p<0.0001), and its secondary endpoint, a >50% reduction in total symptom score at 24 weeks (p<0.0001).

Phase 3 Primary Endpoint Significant Reduction in Spleen Size at Week 24

Response Rate
% of patients with ≥35% reduction in spleen volume by MRI at week 24

Placebo
n=95

Fedratinib
400 mg
n=96
Fedratinib
500 mg
n=97
All patients 1 47 49
Patients with platelets <100X109/L 0 36 40
Patients with platelets >100X109/L 1 49 51
p<0.0001

Phase 3 Secondary Endpoint Significant Reduction in Total Symptom Score

Total Symptom Score*
% of patients with reduction ≥50% at 24 weeks

Placebo
n=95

Fedratinib
400 mg
n=96
Fedratinib
500 mg
n=97
All patients 7 36 34
Patients with platelets <100X109/L 9 40 37
Patients with platelets >100X109/L 0 23 20
p<0.0001

* Total Symptom Score=average value of the daily total score of patient assessment of night sweats, pruritus, abdominal discomfort, early satiety, pain under ribs and bone or muscle pain

In a separate Phase 2 trial evaluating fedratinib in patients who were ruxolitinib resistant or intolerant, 55% of the patients had a >35% reduction in spleen size.

The most common adverse events for fedratinib were hematological (anemia, thrombocytopenia) and gastrointestinal (nausea, diarrhea and vomiting).

In 2013, the development of fedratinib was discontinued by Sanofi after the FDA issued a clinical hold subsequent to reports of a few potential cases of Wernicke’s encephalopathy (WE), an acute neurological condition usually indicative of a vitamin B deficiency, in patients participating in fedratinib clinical trials. Following a Type A meeting and review of additional data, the FDA concluded that Impact provided the necessary documentation to support lifting the clinical hold – opening the path for Impact’s continued development of fedratinib.

Please click here to view a listing of available presentations and publications.

Scroll To Top

Myeloproliferative Neoplasms

Myeloproliferative Neoplasms (MPN) are a closely-related group of blood cancers in which the body, specifically the bone marrow, makes too many red blood cells, platelets, or certain white blood cells.

There are three types of blood cancers that comprise MPNs:

  1. Myelofibrosis (MF) is a serious bone marrow disorder that disrupts the body’s normal production of blood cells. The result is extensive scarring in the bone marrow often with debilitating symptoms such as splenomegaly (enlarged spleen), hepatomegaly (enlarged liver), anemia, fever, bone pain, fatigue, weight loss, pruritus and night sweats. For intermediate-high risk patients, MF is associated with one to three-year survival rates.
  2. Polycythemia Vera (PV) is a slow-growing blood cancer in which the bone marrow makes too many red blood cells. These excess cells thicken blood, slowing its flow which often leads to complications such as blood clots, which can lead to a heart attack or stroke.
  3. Essential Thrombocythemia (ET) is characterized by the production of too many blood platelets resulting in fatigue, lightheadedness, headaches and vision changes. It also increases risk of blood clots.

Scroll To Top

Pipeline

Scroll To Top

Fedratinib

Myeloproliferative Neoplasms (MPN) are characterized by the mutations of JAK2, MPL or CALR. As shown in the figure, the mutational activation of JAK2 is the primary MPN disease driver.

Equipped with this knowledge and supporting clinical studies, we are developing fedratinib, a potent and targeted oral small molecule JAK2 kinase inhibitor for the treatment of myelofibrosis (MF) and polycythemia vera (PV).

Beyond MPNs, fedratinib has potential applications in the treatment of acute myeloid leukemia (AML) and colorectal cancer (CRC).

Sanofi completed a Phase 3 placebo-controlled trial with fedratinib for the first-line treatment of myelofibrosis. A total of 288 subjects were randomized to receive 400mg or 500mg daily of fedratinib or placebo. Fedratinib achieved its primary endpoint, a >35% reduction in spleen size at week 24 (p<0.0001), and its secondary endpoint, a >50% reduction in total symptom score at 24 weeks (p<0.0001).

Phase 3 Primary Endpoint Significant Reduction in Spleen Size at Week 24

Response Rate
% of patients with ≥35% reduction in spleen volume by MRI at week 24
Placebo
n=95

Fedratinib
400 mg
n=96
Fedratinib
500 mg
n=97
All patients 1 47 49
Patients with platelets <100X109/L 0 36 40
Patients with platelets >100X109/L 1 49 51
p<0.0001

Phase 3 Secondary Endpoint Significant Reduction in Total Symptom Score

Total Symptom Score*
% of patients with reduction ≥50% at 24 weeks

Placebo
n=95

Fedratinib
400 mg
n=96
Fedratinib
500 mg
n=97
All patients 7 36 34
Patients with platelets <100X109/L 9 40 37
Patients with platelets >100X109/L 0 23 20
p<0.0001

* Total Symptom Score=average value of the daily total score of patient assessment of night sweats, pruritus, abdominal discomfort, early satiety, pain under ribs and bone or muscle pain

In a separate Phase 2 trial evaluating fedratinib in patients who were ruxolitinib resistant or intolerant, 55% of the patients had a >35% reduction in spleen size.

The most common adverse events for fedratinib were hematological (anemia, thrombocytopenia) and gastrointestinal (nausea, diarrhea and vomiting).

In 2013, the development of fedratinib was discontinued by Sanofi after the FDA issued a clinical hold subsequent to reports of a few potential cases of Wernicke’s encephalopathy (WE), an acute neurological condition usually indicative of a vitamin B deficiency, in patients participating in fedratinib clinical trials. Following a Type A meeting and review of additional data, the FDA concluded that Impact provided the necessary documentation to support lifting the clinical hold – opening the path for Impact’s continued development of fedratinib.

Please click here to view a listing of available presentations and publications.

Scroll To Top

Myeloproliferative Neoplasms

Myeloproliferative Neoplasms (MPN) are a closely-related group of blood cancers in which the body, specifically the bone marrow, makes too many red blood cells, platelets, or certain white blood cells.

There are three types of blood cancers that comprise MPNs:

  1. Myelofibrosis (MF) is a serious bone marrow disorder that disrupts the body’s normal production of blood cells. The result is extensive scarring in the bone marrow often with debilitating symptoms such as splenomegaly (enlarged spleen), hepatomegaly (enlarged liver), anemia, fever, bone pain, fatigue, weight loss, pruritus and night sweats. For intermediate-high risk patients, MF is associated with one to three-year survival rates.
  2. Polycythemia Vera (PV) is a slow-growing blood cancer in which the bone marrow makes too many red blood cells. These excess cells thicken blood, slowing its flow which often leads to complications such as blood clots, which can lead to a heart attack or stroke.
  3. Essential Thrombocythemia (ET) is characterized by the production of too many blood platelets resulting in fatigue, lightheadedness, headaches and vision changes. It also increases risk of blood clots.

Scroll To Top

Pipeline

Scroll To Top

Fedratinib

Myeloproliferative Neoplasms (MPN) are characterized by the mutations of JAK2, MPL or CALR. As shown in the figure, the mutational activation of JAK2 is the primary MPN disease driver.

Equipped with this knowledge and supporting clinical studies, we are developing fedratinib, a potent and targeted oral small molecule JAK2 kinase inhibitor for the treatment of myelofibrosis (MF) and polycythemia vera (PV).

Beyond MPNs, fedratinib has potential applications in the treatment of acute myeloid leukemia (AML) and colorectal cancer (CRC).

Sanofi completed a Phase 3 placebo-controlled trial with fedratinib for the first-line treatment of myelofibrosis. A total of 288 subjects were randomized to receive 400mg or 500mg daily of fedratinib or placebo. Fedratinib achieved its primary endpoint, a >35% reduction in spleen size at week 24 (p<0.0001), and its secondary endpoint, a >50% reduction in total symptom score at 24 weeks (p<0.0001).

Phase 3 Primary Endpoint Significant Reduction in Spleen Size at Week 24

Please scroll
Response Rate
% of patients with ≥35% reduction in spleen volume by MRI at week 24
Placebo
n=95






Fedratinib
400 mg
n=96





Fedratinib
500 mg
n=97





All patients 1 47 49
Patients with platelets <100X109/L 0 36 40
Patients with platelets >100X109/L 1 49 51
p<0.0001

Phase 3 Secondary Endpoint Significant Reduction in Total Symptom Score

Please scroll
Total Symptom Score*
% of patients with reduction ≥50% at 24 weeks
Placebo
n=95







Fedratinib
400 mg
n=96






Fedratinib
500 mg
n=97






All patients 7 36 34
Patients with platelets <100X109/L 9 40 37
Patients with platelets >100X109/L 0 23 20
p<0.0001

* Total Symptom Score=average value of the daily total score of patient assessment of night sweats, pruritus, abdominal discomfort, early satiety, pain under ribs and bone or muscle pain

In a separate Phase 2 trial evaluating fedratinib in patients who were ruxolitinib resistant or intolerant, 55% of the patients had a >35% reduction in spleen size.

The most common adverse events for fedratinib were hematological (anemia, thrombocytopenia) and gastrointestinal (nausea, diarrhea and vomiting).

In 2013, the development of fedratinib was discontinued by Sanofi after the FDA issued a clinical hold subsequent to reports of a few potential cases of Wernicke’s encephalopathy (WE), an acute neurological condition usually indicative of a vitamin B deficiency, in patients participating in fedratinib clinical trials. Following a Type A meeting and review of additional data, the FDA concluded that Impact provided the necessary documentation to support lifting the clinical hold – opening the path for Impact’s continued development of fedratinib.

Please click here to view a listing of available presentations and publications.

Scroll To Top

Myeloproliferative Neoplasms

Myeloproliferative Neoplasms (MPN) are a closely-related group of blood cancers in which the body, specifically the bone marrow, makes too many red blood cells, platelets, or certain white blood cells.

There are three types of blood cancers that comprise MPNs:

  1. Myelofibrosis (MF) is a serious bone marrow disorder that disrupts the body’s normal production of blood cells. The result is extensive scarring in the bone marrow often with debilitating symptoms such as splenomegaly (enlarged spleen), hepatomegaly (enlarged liver), anemia, fever, bone pain, fatigue, weight loss, pruritus and night sweats. For intermediate-high risk patients, MF is associated with one to three-year survival rates.
  2. Polycythemia Vera (PV) is a slow-growing blood cancer in which the bone marrow makes too many red blood cells. These excess cells thicken blood, slowing its flow which often leads to complications such as blood clots, which can lead to a heart attack or stroke.
  3. Essential Thrombocythemia (ET) is characterized by the production of too many blood platelets resulting in fatigue, lightheadedness, headaches and vision changes. It also increases risk of blood clots.

Scroll To Top