publication date: Dec. 3, 2013


Drug Approvals

FDA Grants Accelerated Approval to Imbruvica

FDA granted an accelerated approval to Imbruvica (ibrutinib) for mantle cell lymphoma patients who have received at least one prior therapy.

Imbruvica was approved four months after submission of its New Drug Application. The agent is sponsored by Pharmacyclics Inc.

The drug received the Breakthrough Therapy designation due to the overall response rate and duration of response seen in the phase II study, PCYC-1104, and the serious and life-threatening nature of MCL.

With approval, it becomes the second Breakthrough Therapy to get on the market.

On Nov. 1, the agency approved the Genentech agent Gazyva (obinutuzumab) for previously untreated chronic lymphocytic leukemia. Altogether, 32 agents have been granted the Breakthrough Therapy designation since the designation was established in July 2012.

The Imbruvica approval was based on the results of a multi-center, international, single-arm trial of 111 patients with previously treated mantle cell lymphoma.

Tumor response was assessed according to the revised International Working Group for non-Hodgkin lymphoma criteria. 

The efficacy results demonstrated a 65.8 percent overall response rate (95% CI: 56.2, 74.5); 17 percent of patients achieved a complete response and 49 percent of patients achieved a partial response.  The median duration of response was 17.5 months (95% CI: 15.8, not reached). 

Safety was evaluated in the same 111 patients.

The most common Grade 3 or 4 non-hematological adverse reactions were: pneumonia, abdominal pain, atrial fibrillation, diarrhea, fatigue, and skin infections. Five percent of patients had Grade 3 or higher bleeding events, such as subdural hematoma, gastrointestinal bleeding, and hematuria.

Treatment-emergent Grade 3 or 4 cytopenias were reported in 41 percent of patients. The Warnings and Precautions listed in the Prescribing Information include hemorrhage, infections, myelosuppression, renal toxicity, second primary malignancies and embryo-fetal toxicity.

Ten patients discontinued treatment due to adverse reactions in the trial. Adverse reactions leading to dose reduction occurred in 14 percent of patients.

As a condition of the accelerated approval, FDA required that the sponsor submit 24-month follow-up data for all patients in the single-arm trial and submit the results of a randomized controlled trial comparing Imbruvica in combination with bendamustine plus rituximab to bendamustine plus rituximab in patients with newly diagnosed MCL.

Prescribing information is available on the FDA website.

The company said FDA is reviewing Imbruvica on an expedited basis for relapsed chronic lymphatic leukemia.

Imbruvica inhibits the function of Bruton’s tyrosine kinase, a signaling molecule of the B-cell receptor signaling complex that plays an important role in the survival of malignant B cells.

“This is a meaningful day for previously treated mantle cell lymphoma patients, who are in need of new treatment options,” said Michael Wang, of the Department of Lymphoma/Myeloma at MD Anderson Cancer Center, lead investigator for the registration trial PCYC-1104. 

Imbruvica is commercially available immediately.

“After observing early signs of efficacy and tolerability of Imbruvica four years ago, we single-mindedly focused our attention on fully developing this medicine,” Bob Duggan, CEO and Chairman of the Board of Pharmacyclics, said in a statement.

“We continue to explore Imbruvica’s potential to treat cancer patients in need. Presently we are in the midst of investigating this medicine in numerous additional B-cell malignancies with 37 clinical studies ongoing.”

A breakthrough therapy is a drug: 

• Intended alone or in combination with one or more other drugs to treat a serious or life threatening disease or condition and

• Preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

When a drug is designated as breakthrough therapy, FDA expedites the development and review of such drug.  All requests for breakthrough therapy designation will be reviewed within 60 days of receipt.

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