U.S. FDA accepts a new generation of PI3Kδ inhibitor/new CD20 monoclonal antibody combination

TG Therapeutics is a biopharmaceutical company dedicated to the development of innovative therapies for B cell-mediated diseases
.

Recently, the company announced that the U.

If approved, the U2 regimen will provide a new, chemotherapy-free regimen for patients with relapsed/refractory (treated) CLL/SLL who have not previously received treatment (initial treatment) and previously received treatment
.

In the U2 protocol, ublituximab is a new glycoengineered anti-CD20 monoclonal antibody that targets a unique epitope of the CD20 antigen on mature B lymphocytes

In February 2021, Ukoniq (umbralisib, 200mg tablets) received accelerated approval from the US FDA for the treatment of: (1) Patients who have received at least one relapsed or refractory marginal zone lymphoma (MZL) based on an anti-CD20 regimen (2) Adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least 3 systemic therapies
.

In terms of medication, the recommended dose of Ukoniq is 800mg (4 tablets), taken once a day orally with food

It is worth mentioning that Ukoniq is the first and only oral, once-daily, phosphoinositide-3-kinase δ (PI3K-δ) and casein kinase 1 approved for the treatment of relapsed/refractory MZL and FL.
-ε (CK1-ε) dual inhibitor
.

U2 BLA is based on the positive results of the global phase III UNITY-CLL trial
.

The trial was carried out in patients with previously untreated (naïve) and relapsed/refractory (treated) chronic lymphocytic leukemia (CLL).

The detailed data of the trial was announced at the American Society of Hematology (ASH) annual meeting in December 2020
.

The results showed that the trial reached the primary endpoint: According to the independent review committee (IRC) assessment, a median follow-up of 36.

It is particularly worth mentioning that the improvement in PFS of the U2 regimen compared with the O+Chl regimen was consistent in all subgroups tested, including newly-treated patients (median PFS: 38.
5 months vs 26.
1 months, HR=0.
482 ) And relapsed/refractory patients (median PFS: 19.
5 months vs 12.
9 months, HR=0.
601)
.

In addition, the overall response rate (ORR) of the U2 group was significantly higher than that of the O+Chl group (ORR: 83.
3% vs 68.
7%; p<0.
001)
.

In terms of safety, for the U2 group, when the median treatment exposure time is 21 months, the severity of most adverse events (AE) is grade 1 or 2, and it is relatively between the newly treated and treated patients Balance

UNITY-CLL test data

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia.
It is estimated that in 2020, 45,000 new cases of CLL will be diagnosed worldwide
.

Although the symptoms and signs of CLL may disappear for a while after the initial treatment, the disease is considered incurable and many patients will require additional treatment due to the recurrence of malignant cells

Ublituximab is a new type of glycoengineered anti-CD20 monoclonal antibody that targets a unique epitope of CD20 antigen on mature B lymphocytes.
This epitope is different from many CD20 monoclonal antibodies currently on the market, including ofatumumab, ocrelizumab/rituximab, obinutuzumab (GA101)
.

Currently, ublituximab is in phase III clinical development for the treatment of CLL and multiple sclerosis (MS)

Umbralisib is a dual-acting inhibitor of PI3Kδ and CK-1ε, which may allow it to overcome some of the tolerance issues associated with the first generation of PI3Kδ inhibitors
.
Phosphatidylinositol-3 kinase (PI3K) is a class of enzymes involved in cell proliferation and survival, cell differentiation, intracellular transport and immunity and other cellular functions
.
PI3K has four subtypes (α, β, δ, and γ), among which the δ subtype is strongly expressed in cells of hematopoietic origin and is often associated with B-cell-associated lymphoma
.

Umbrasib has nanomolar potency for the delta subtype of PI3K, and has high selectivity for the alpha, beta, and gamma subtypes
.
Umbralisib also uniquely inhibits casein kinase 1-ε (CK1-ε), which may have a direct anti-cancer effect, and may also modulate T cell activity associated with immune-mediated adverse events observed in previous PI3K inhibitors
.

The currently approved PI3Kδ inhibitors are related to autoimmune-mediated toxicity, such as liver toxicity, pulmonary toxicity, and colitis
.
Compared with the approved PI3K inhibitors, the specific difference of umbralisib, its unique inhibitory effect on CK1-ε, and its unique and patented chemical structure may have different characteristics in the PI3K inhibitor class
.

Original source: TG Therapeutics Announces FDA Acceptance of Biologics License application for Ublituximab in Combination with UKONIQ (umbralisib) as a Treatment for Patients with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Original title: Leukemia bid farewell to chemotherapy! The U.
S.
FDA accepts a new generation of PI3Kδ inhibitor/new CD20 monoclonal antibody combination (umbralisib+Ukoniq)!