FDA Receives Biologics License Application for Combination Treatment for CLL

TG Therapeutics has been developing ublituximab as a treatment for chronic lymphocytic leukemia (CLL) when used in combination with umbralisib, marketed as UKONIQ. The biopharmaceutical company has recently completed and submitted its rolling Biologics License Application (BLA) to the FDA and is now waiting for a response. This was possible after a Phase 3 trial of ublituximab, titled UNITY-CLL, demonstrated positive results.

About CLL

Chronic lymphocytic leukemia is a rare cancer of the bone marrow and blood. Affected individuals do not have properly functioning bone marrow, as it produces abnormal white blood cells – specifically lymphocytes – which then crowd out healthy cells. Doctors are unsure as to why this happens; all they know is that a genetic mutation occurs for some reason within the blood-producing cells of the bone marrow. Regardless of the cause, CLL causes symptoms like night sweats, fever, fatigue, weight loss, enlarged spleen, pain in the abdomen, frequent infections, and enlarged but painless lymph nodes. After diagnosing this cancer, treatment options consist of chemotherapy, targeted therapy, and a bone marrow transplant.

Ublituximab as a Treatment for CLL

The completion of the BLA comes after the FDA granted ublituximab Fast Track and Orphan Drug designations when used in combination with umbralisib in adult CLL patients, along with the results of the UNITY-CLL trial.

Designations for Ublituximab

The Fast Track designation is intended to speed up the pace at which drugs are developed and reviewed so that they can reach patients sooner. It is reserved for therapies that treat severe conditions facing an unmet medical need. Upon receiving this designation, TG Therapeutics receives rolling submission for either a New Drug Application (NDA) or BLA, increased contact with the FDA, and priority review.

Turning to the Orphan Drug designation, it is granted to therapies that treat, prevent, or diagnose rare conditions. A rare disease is defined as one that impacts fewer than 200,000 people in the United States. The benefits of this designation include orphan product exclusivity if approved, fee waivers, and tax credits.


This global, Phase 3 trial first compared the combination of ublituximab and umbralisib to a control combination of obinutuzumab plus chlorambucil. CLL patients with refractory or relapsed were included in the trial, as were patients who had never before received treatment. These patients were randomly placed into four arms:

  1. Treatment with ublituximab as a single agent
  2. Treatment with umbralisib as a single agent
  3. Combination treatment of ublituximab and umbralisib
  4. Combination treatment of obinutuzumab and chlorambucil

After this portion of the trial was analyzed, researchers were able to eliminate the single-arm groups. Moving forward, the 420 participants were randomized 1:1 and placed into one of the two trial arms. Researchers focused on the primary endpoint, which was progression-free survival (PFS). This endpoint was met, which is exciting for medical professionals and patients alike.

Looking Forward

TG Therapeutics is very pleased with the results of the UNITY-CLL trial, and they look forward to working closely with the FDA on approval. If this combination is approved, it would bring the first regimen that treats CLL patients with refractor/relapsed and treatment naïve disease.

Read more here.

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