TG Therapeutics reports development for Umbralisib

TG Therapeutics Inc. (TGTX) reported that the FDA has accepted its New Drug Application for umbralisib. The drug candidate will be reviewed under the Priority Review pathway. It had been granted Breakthrough Therapy tag for treating marginal zone lymphoma condition. Its Prescription Drug User Fee Act (PDUFA) goal date has been set at February 15, 2021. For follicular lymphoma, the drug candidate will undergo standard review and the PDUFA goal date of June 15, 2021, has been set.

TG Therapeutics has used data from the umbralisib monotherapy MZL and FL cohorts of the UNITY-NHL Phase 2b trial for supporting its NDA. The trial was set to assess the potential of umbralisib in treating patients suffering from marginal zone lymphoma or follicular lymphoma. Michael S. Weiss of TG Therapeutics said:

If approved, we believe umbralisib could become an important treatment option for patients with previously treated MZL and FL. We look forward to presenting the data from the UNITY-NHL trial that supported this NDA submission by year end."

TG Therapeutics had earlier reported that each cohort of the trial had met its primary endpoint pertaining overall response rate. The company's target guidance was pegged at 40 to 50 percent ORR and its achievement was confirmed by an Independent Review Committee. The drug candidate was tagged as an orphan drug for both the indications of MZL and FL.

The UNITY-NHL trial is a global multicenter, open-label Phase 2b trial. Its MZL cohort aimed to assess the safety and efficacy of single-agent umbralisib in patients with MZL who have been administered at least one prior anti-CD20 regimen. All treated MZL patients met the primary endpoint of overall response rate.

The follicular Lymphoma cohort aimed to assess the safety and efficacy of single-agent umbralisib in patients with FL who were relapsed or refractory following at least two prior lines of therapy, including an anti-CD20 regimen and an alkylating agent. All treated FL patients also met the primary endpoint of ORR. The results were also in line with the company's pre-decided response target of 40 to 50 percent ORR.

On June 15, 2020, TG Therapeutics reported that it has completed the rolling submission of an NDA to the FDA. The company had requested the FDA for accelerated approval of the drug candidate for treating patients with previously treated MZL and FL. The company's request has now been accepted by the FDA.

TG Therapeutics is mainly invested in acquiring, developing, and commercializing treatments for various autoimmune diseases and B-cell malignancies. The company currently has two investigational compounds in late-stage clinical development phase. These two compounds are ublituximab and umbralisib and they target autoimmune ailments and hematological malignancies.

Ublituximab is a glycoengineered monoclonal antibody and works by targeting a particular epitope on the CD20 antigen found on mature B-lymphocytes. Umbralisib is an oral dual inhibitor and is designed to be taken once a day daily. TG Therapeutics has a robust development pipeline with two fully enrolled identical Phase 3 trials evaluating ublituximab monotherapy in patients with relapsing forms of multiple sclerosis.

Mesoblast Limited (MESO) announced that the Oncologic Drugs Advisory Committee of the FDA has voted in favor of Ryoncil in pediatric patients with steroid-refractory acute graft versus host disease. The ODAC is an independent panel of experts that assesses the efficacy and safety of data for the purpose of making appropriate recommendations to the FDA.

The news has come as a surprise to many industry experts as the company had been marred with several issues pertaining to the drug candidate. It has been noted that the review team had raised concerns regarding the data presented by the company with its application. The committee had raised concerns that the main pediatric study, MSB-GVHD001, allowed the use of other agents, which might have compromised the outcomes.

While the FDA takes committee recommendation into account while delivering the final verdict, it has no obligation to follow such recommendation. Dr. Fred Grossman of Mesoblast said:

We are very encouraged by today's outcome and are committed to working closely with the FDA as they complete their review of our submission regarding approval of RYONCIL for this life-threatening complication of an allogeneic bone marrow transplant."

The drug candidate has been given an action date of September 30, 2020, under the Prescription Drug User Fee Act.

Ryoncil is the lead drug candidate for Mesoblast. It is an investigational therapy comprising culture-expanded mesenchymal stem cells. These cells are taken from the bone marrow of an unrelated donor. The drug candidate is deemed to have immunomodulatory properties for counteracting the inflammatory processes. These processes may down regulate the production of pro-inflammatory cytokines and thus may expand the production of anti-inflammatory cytokines and allowing recruitment of naturally occurring anti-inflammatory cells to involved tissues.

Imara Inc. (IMRA) announced the dosing of the first patient for the company's Ardent Phase 2b clinical trial of IMR-687 for adult patients with sickle cell disease. The company had earlier reported the data from the second planned interim analysis of Phase 2a clinical trial of IMR-687. The company is looking to report top-line data from this Phase 2a clinical trial in the fourth quarter of 2020.

IMR-687 Phase 2b Clinical Trial is a global, randomized, double-blind, placebo-controlled, multicenter study under the name of Ardent. The study will have nearly 99 adult patients suffering from sickle cell disease and will be randomized using hydroxyurea and the region. Doses will be based on weight to optimize tolerability and drug exposure.

The primary efficacy objective of the trial is to assess the proportion of all patients with fetal hemoglobin (HbF) response. The endpoint has been defined as an increase of 3% in HbF from baseline to week 24, compared to placebo. Rahul Ballal, CEO of Imara said:

Dosing of the first patient in the Ardent clinical trial represents a critical step forward as we advance IMR-687 into Phase 2b testing, a clinical trial that will test higher doses and longer durations of IMR-687."

During the trial, the patients will be kept on treatment through 52 weeks to gather data for planned secondary and additional exploratory endpoints. Some of these endpoints are indices of red cell hemolysis, quality of life measures, and HbF-associated biomarkers. Once the period of 52 weeks of treatment is over, patients will be entitled to be enrolled in an open-label extension study.

IMR-687 is a highly selective and potent small-molecule inhibitor of PDE9. People suffering from SCD and beta-thalassemia generally have lower levels of cGMP and may experience greater cell adhesion and reduced blood flow in addition to the decline in nitric oxide-mediated vasodilation.

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