Incyte has withdrawn its New Drug Application (NDA) for parsaclisib, which is an investigational treatment for various types of lymphoma, including relapsed/refractory mantle cell lymphoma (MCL), follicular lymphoma, and marginal zone lymphoma (MZL). The company did not have enough time to submit the confirmatory studies requested by the FDA, so they withdrew the application completely.

Withdrawing the NDA

Parsaclisib is an orally administered PI3Kδ inhibitor developed by Incyte for the treatment of relapsed/refractory MCL, MZL, and follicular lymphoma. It was most recently studied in the Phase 2 CITADEL-205 trial, in which 108 MCL patients enrolled. Patients were separated into one of two groups: those treated with 20 mg of parsaclisib once a day for eight weeks followed by 20 mg once a week, and those treated with a daily dosing regimen followed by a subsequent dose of 2.5 mg.

The study analysis revealed the following results:

• Within the 108 participants, there was an overall response rate (ORR) of 68.5%
  • The complete response rate was 17.6%
• Within the group on the daily dosing regimen, there was an ORR of 70.1%
  • The complete response rate was 15.6%
• Within the patients who responded to treatment, the majority (89.2%) did so by the first disease assessment
• The median duration of response was 13.7 months within the total study population
  • It was 12.1 months in those treated with the daily dosing regimen
• The median progression-free survival within all 108 patients was 11.99 months
  • Within the daily dosing group, it was 13.6 months
• Treatment-emergent adverse events (TEAEs) occurred in 90.7% of participants
  • 62.0% reported TEAEs grade 3 or higher
  • The most common TEAEs were constipation, diarrhea, hypokalemia, and pyrexia
    • Colitis, diarrhea, and hypokalemia were the TEAEs most likely to cause patients to discontinue

Despite the data gathered in this trial, the FDA wanted to see confirmatory studies in order to grant accelerated approval. Incyte could not complete this in a timely manner, so they instead withdrew the NDA.

This decision only impacts the U.S. indications of follicular lymphoma, MCL, and MZL. Additionally, Incyte stresses that this choice was one driven by business; parsaclisib’s efficacy and safety profiles remain unchanged.

About Follicular Lymphoma

Follicular lymphoma is a form of non-Hodgkin’s lymphoma, and it is typically a slow-growing cancer. It tends to impact those above the age of 60 and accounts for one of every five cases of lymphoma. This cancer occurs when the DNA of B-cells mutates, making them grow and divide rapidly. These abnormal cells then crowd out the healthy ones, causing the characteristic symptoms and lowering the body’s ability to fight infections.

Symptoms include:

• Fever
• Night sweats
• Swollen lymph nodes
• Shortness of breath
• Weight loss

About Mantle Cell Lymphoma (MCL)

MCL is a form of non-Hodgkin’s lymphoma that forms in the region of lymphocytes known as the mantle zone. Medical professionals are unsure as to why these lymphocytes become malignant and multiply out of control, but they do know that something triggers the release of the cyclin D1 protein, which causes B-cell growth and leads to MCL.

Symptoms of this cancer typically begin with swelling of the lymph nodes in the neck, shoulders, elbows, and chest. Other effects include bowel issues, fever, nausea, vomiting, indigestion, bloating, heartburn, unintentional weight loss, pressure/pain in the lower back, lack of appetite, and a false sense of fullness. This cancer may spread throughout the body, and if it reaches the brain or spinal cord, additional symptoms may include poor balance, headaches, confusion, irritability, dizziness, and personality changes. Treatment may consist of monitoring if one’s cancer is in its earlier stages. Upon progression, treatment options are stem cell transplants, chemotherapy, targeted therapy, and immunotherapy.

About Marginal Zone Lymphoma (MZL)

MZL is a form of non-Hodgkin’s lymphoma (NHL) that develops in a region of the lymph nodes called the mantle zone. It is an indolent B-cell lymphoma that can be separated into three types: nodal, extranodal, and splenic. The first symptom to appear is typically swelling in affected areas, which is followed by nausea, vomiting, unexplained weight loss, repeated fevers, heartburn, bloating, indigestion, a sense of fullness, and a lack of appetite.

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