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FDA News January 2020

TOP - January 2020, Vol 13, No 1 - FDA Updates

NEW DRUGS

Brukinsa Receives Accelerated FDA Approval for Mantle-Cell Lymphoma

On November 14, 2019, the FDA granted accelerated approval to zanubrutinib capsules (Brukinsa; BeiGene), a Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of adults with mantle-cell lymphoma who have received at least 1 previous therapy. This is the second BTK inhibitor to be approved by the FDA.

“Mantle cell lymphoma usually responds well to initial treatment, but eventually returns or stops responding, and the cancer cells continue to grow. This is a life-threatening condition,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence. “Clinical trials showed that 84% of patients saw tumor shrinkage with this therapy. For patients whose disease relapses or becomes refractory, secondary therapies may be successful in providing another remission, and today’s approval will provide patients with another treatment option.”

The FDA designated zanubrutinib as a breakthrough therapy and an orphan drug. Mantle-cell lymphoma represents 3% to 10% of all non-Hodgkin lymphoma cases in the United States.

This approval was based on a phase 2 open-label, multicenter, single-arm clinical trial of 86 patients with mantle-cell lymphoma who had received at least 1 previous therapy. The overall response rate (ORR) was 84% (95% confidence interval [CI], 74-91), with a complete response rate of 59% (95% CI, 48-70) and a median duration of response of 19.5 months (95% CI, 16.6-not estimable). This approval was also based on an earlier phase 1/2 open-label, dose-escalation, multicenter, single-arm clinical trial of 32 patients with mantle-cell lymphoma who had received at least 1 previous therapy. The ORR was 84% (95% CI, 67-95), with a complete response rate of 22% (95% CI, 9-40) and a median duration of response of 18.5 months (95% CI, 12.6-not estimable).

The most common (≥20%) side effects with zanubrutinib were reduced neutrophils, decreased platelets, upper respiratory tract infection, decreased white blood cells, decreased hemoglobin level, rash, bruising, diarrhea, and cough. The most common serious adverse reactions were pneumonia (11%) and hemorrhage (5%).

Ziextenzo Third Biosimilar to Neulasta Approved for Febrile Neutropenia

On November 5, 2019, the FDA approved pegfilgrastim-bmez (Ziextenzo; Sandoz) as a third biosimilar to Neulasta (pegfilgrastim), a granulocyte colony-stimulating factor. The previous 2 biosimilars to Neulasta were approved in 2018.

Pegfilgrastim-bmez is approved for the same indications as its reference drug—to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies who receive myelosuppressive drugs (which are associated with an increased risk for febrile neutropenia). Pegfilgrastim-­bmez is not approved for the mobilization of peripheral blood progenitor cells for hematopoietic stem-cell transplant.

The FDA approval of pegfilgrastim-bmez was based on data showing that it is highly similar to its reference drug, and that there are no clinically meaningful differences between these 2 drugs.

NEW INDICATIONS

Tecentriq Approved with Chemotherapy for First-Line Treatment of Metastatic NSCLC without EGFR or ALK Mutations

On December 3, 2019, the FDA approved atezolizumab (Tecentriq; Genentech), in combination with paclitaxel protein-bound (Abraxane) and carboplatin chemotherapy, for the first-line treatment of adults with metastatic nonsquamous non–small-cell lung cancer (NSCLC) that does not harbor EGFR or ALK genomic mutations.

This approval was based on results of the IMpower130 study, a multicenter, randomized, open-label clinical trial of patients with stage IV nonsquamous NSCLC who did not receive any chemotherapy for metastatic disease; the patients could have received a previous EGFR or ALK inhibitor, if appropriate. A total of 724 patients were randomized to atezolizu­mab, paclitaxel protein-­bound, and carboplatin, followed by monotherapy with atezolizumab or to paclitaxel protein-­bound and carboplatin, followed by maintenance therapy with pemetrexed.

In the primary analysis of 681 patients without EGFR or ALK mutations, the estimated median progression-free survival was 7.2 months (95% confidence interval [CI], 6.7-8.3) with atezolizumab versus 6.5 months (95% CI, 5.6-7.4) in the control arm (hazard ratio, 0.75; 95% CI, 0.63-0.91; P = .0024). The median overall survival was 18.6 months (95% CI, 15.7-21.1) versus 13.9 months (95% CI, 12.0-18.7), respectively (P = .0384).

The most common (≥20%) adverse events with atezolizumab plus chemotherapy in patients with nonsquamous NSCLC were fatigue/asthenia, nausea, alopecia, constipation, diarrhea, and decreased appetite.

FDA Approves Calquence for Adults with CLL or SLL

On November 21, 2019, the FDA accelerated the approval of acalabru­tinib (Calquence; AstraZeneca) for adults with chronic lymphocytic leukemia (CLL) or with small lymphocytic lymphoma. This drug was approved 4 months earlier than the FDA PDUFA date. The FDA used its priority review for these 2 indications and granted acalabrutinib a breakthrough therapy designation for these indications.

This approval was done under Project Orbis, a new initiative by the FDA’s Oncology Center of Excellence. Project Orbis provides a framework for the concurrent submission and review of cancer drugs among international partners. The FDA, the Australian Therapeutic Goods Administration, and Health Canada collaborated on this review.

“Today, as part of a US, Australian, and Canadian collaboration known as Project Orbis, the US approved a new treatment option for those living with chronic lymphocytic leukemia or small lymphocytic lymphoma. The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international partners,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence.

The approval was based on results of 2 randomized, actively controlled clinical trials.

The ELEVATE-TN study included 535 newly diagnosed patients with CLL who were randomized to 1 of 3 arms: acalabrutinib monotherapy, acalabrutinib plus obinutuzumab, or obi­nutuzu­mab plus chlorambucil. With a median follow-up of 28.3 months, the hazard ratio (HR) for progression-free survival (PFS) was 0.10 (95% confidence interval [CI], 0.06-0.17; P <.0001) with acalabrutinib plus obinutuzumab and 0.20 (95% CI, 0.13-0.30; P <.0001) with acalabrutinib monotherapy compared with obinutuz­umab plus chlorambucil.

The ASCEND study randomized 310 patients with relapsed or refractory CLL who received at least 1 systemic therapy to acalabrutinib or to the investigator’s choice of treatment (idelalisib plus rituximab therapy, or bendamustine plus rituximab therapy). With a median follow-up of 16.1 months, the PFS was significantly longer in the acalabrutinib monotherapy arm compared with the investigator’s choice arm (HR, 0.31; 95% CI, 0.20-0.49; P <.0001).

In both studies, with a median follow-up of 28.3 months, the median PFS had not been reached in the acalabrutinib arm, and the median overall survival had not been reached in any arm.

The most common (≥30%) adverse reactions of any grade in patients with CLL were anemia, neutropenia, thrombocytopenia, headache, upper respiratory tract infection, and diarrhea.

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Last modified: January 22, 2020