The Year in FDA Approvals

In the past year, the U.S. Food and Drug Administration (FDA) approved a record-breaking number of drugs, several of which were indicated for the treatment of lymphoid malignancies. Here, we review the regulatory approvals from the last year, including the first treatment approved through a new expedited review process and the first biosimilar version of rituximab.

Mogamulizumab

On August 8, 2018, the FDA approved mogamulizumab-kpkc for patients with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) – two rare forms of non-Hodgkin lymphoma (NHL) – after at least one prior systemic therapy. This approval marks the first FDA-approved option for patients with SS.

Mogamulizumab-kpkc is a CC chemokine receptor type 4 (CCR4)–directed monoclonal antibody. Its approval was based on results from a randomized, open-label, multicenter clinical trial of 372 patients with relapsed or refractory MF or SS.

Median progression-free survival (PFS) was longer for patients receiving mogamulizumab-kpkc than for patients receiving the histone deacetylase inhibitor vorinostat: 7.6 months versus 3.1 months (ranges and p value not provided). The overall response rate (ORR) was 28 percent and 5 percent, respectively (p<0.001).

Serious adverse events (AEs) occurred in 36 percent of patients, most often from infection (16% in both treatment groups). The prescribing information includes warnings for the risk of dermatologic toxicity, infusion reactions, infections, autoimmune problems, and allogeneic hematopoietic cell transplantation complications.

Brentuximab Vedotin

On November 16, 2018, the FDA approved brentuximab vedotin, in combination with chemotherapy, for the frontline treatment of adult patients with systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified. Brentuximab vedotin is now the first agent approved for this indication.

The agency issued its decision through an expedited review process for oncology products, the Real-Time Oncology Review (RTOR) program. “[This program] allows the FDA to access key data prior to the official submission of the application, allowing the review team to begin their review earlier and communicate with the sponsor prior to the application’s actual submission,” explained Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence.

The decision was based on data from the phase III ECHELON-2 trial, which included 452 patients with CD30-positive PTCL who received chemotherapy with or without brentuximab vedotin. Median PFS was significantly longer in the brentuximab vedotin group (48.2 months vs. 20.8 months; p=0.01). Brentuximab vedotin also improved overall survival (hazard ratio [HR] = 0.66; p=0.024), complete response rates (CRR; 68% vs. 56%; p=0.007), and ORR (83% vs. 72%; p=0.003).

The prescribing information for brentuximab vedotin includes a boxed warning about the risk of a fatal or life-threatening progressive multifocal leukoencephalopathy.

Emapalumab

On November 20, 2018, the FDA approved emapalumab, an anti-interferon gamma monoclonal antibody, for the treatment of adults and children with primary hemophagocytic lymphohistiocytosis (HLH) that was refractory or relapsed or progressed following conventional HLH therapy.

The approval, which also included patients who could not tolerate conventional therapy, was based on results from a multicenter, open-label, single-arm trial, which included 27 pediatric patients who received emapalumab at a starting dose of 1 mg/kg every three days. All participants received dexamethasone as background HLH treatment, at doses ranging between 5 to 10 mg/m2 per day. Patients also received prophylaxis for herpes zoster, Pneumocystis jirovecii, and fungal infections.

At the end of the treatment period, the ORR was 63 percent, including seven CRs and eight partial responses, and two patients who experienced an improvement in HLH (defined as ≥3 HLH abnormalities improved by at least 50 percent from baseline).

The most common AEs were infections, hypertension, infusion-related reactions, and pyrexia.

Rituximab Biosimilar

On November 28, 2018, the FDA approved rituximab-abbs as the first biosimilar to rituximab and for the treatment of adult patients with CD20-positive, B-cell NHL. This is the 15th biosimilar to be approved in the U.S.

The agency’s approval was based on a review of evidence that included extensive structural and functional characterization, animal study data, human pharmacokinetic data, clinical immunogenicity data, and other clinical data that demonstrate rituximab-abbs’s similarity to its reference product. However, the FDA noted that this agent is approved as a biosimilar, not as an interchangeable product.

Like its reference product, rituximab-abbs is indicated for the treatment of adult patients with:

  • relapsed or refractory, low-grade or follicular, CD20- positive B-cell NHL as a single agent
  • previously untreated follicular, CD20-positive, B-cell NHL with firstline chemotherapy or as single-agent maintenance therapy in patients achieving a CR or PR to a rituximab product in combination with chemotherapy
  • non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after firstline cyclophosphamide, vincristine, prednisone chemotherapy

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