NEWLY APPROVED DRUGS
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, in-
cluding 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 pre-
scribing 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).
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Focus on Lymphoid Malignancies
The prescribing information for brentuximab vedotin includes
a boxed warning about the risk of a fatal or life-threatening pro-
gressive 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 lympho-
histiocytosis (HLH) that was refractory or relapsed or pro-
gressed following conventional HLH therapy.
The approval, which also included patients who could not toler-
ate 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/m 2 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 characteriza-
tion, 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 ●