LONDON and COPENHAGEN, Denmark—GlaxoSmithKline plc and Genmab A/S have announced that the U.S. Food and Drug Administration (FDA) has approved a Supplemental Biologic License Application for the use of Arzerra (ofatumumab), a CD20-directed monoclonal antibody, in combination with chlorambucil for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate.
The FDA approval of the first-line indication is based on results from a Phase 3 study (COMPLEMENT 1) which demonstrated statistically significant improvement in median progression-free survival (PFS) in patients who received the combination of ofatumumab and chlorambucil compared to patients who received chlorambucil alone.
"CLL is the most common form of leukemia among adults in Western countries, many of whom are elderly with multiple health issues," said Dr. Paolo Paoletti, president of oncology, GSK. "Today's approval by the FDA for the use of Arzerra in the first-line setting means that appropriate patients with CLL have a new treatment option."
"We are pleased that Arzerra has been shown to provide clinical benefit and will now be available in the first-line setting. Arzerra, the first approved therapeutic created by Genmab and developed in collaboration with GSK, is the only therapeutic CD20 antibody approved in combination with chlorambucil for first-line CLL and as a monotherapy for CLL refractory to fludarabine and alemtuzumab," said Jan van de Winkel, Ph.D., CEO of Genmab.
The results from COMPLEMENT 1, the randomized, open-label, parallel-arm, pivotal Phase 3 study evaluating the combination of ofatumumab and chlorambucil (N=221) versus chlorambucil alone (N=226) demonstrated statistically significant improvement in median PFS in patients randomized to ofatumumab and chlorambucil compared to patients randomized to chlorambucil alone (22.4 months versus 13.1 months, respectively)
The majority of adverse reactions were Grade 2 or lower in both treatment arms. The most common in the ofatumumab plus chlorambucil arm were neutropenia (27 percent ofatumumab + chlorambucil, 18 percent chlorambucil), asthenia (8 percent, 5 percent), headache (7 percent, 3 percent), leukopenia (6 percent, 2 percent), herpes simplex (6 percent, 4 percent), lower respiratory tract infection (5 percent, 3 percent), arthralgia (5 percent, 3 percent), and upper abdominal pain (5 percent, 3 percent). Infusion reactions were seen in 67 percent of patients in the ofatumumab plus chlorambucil arm. Ten percent of IRs were Grade 3 or greater. Infusion reactions that were Grade 3 or greater, serious or led to treatment interruption or discontinuation occurred most frequently with Cycle 1 and decreased with subsequent infusions.
CLL, the most commonly diagnosed adult leukemia in Western countries, accounts for approximately one-third of all cases of leukemia. In the U.S., it is estimated that more than 105,000 people currently live with or have been previously treated for CLL and an estimated 15,680 new cases of CLL were diagnosed in the past year. The average age of diagnosis is 72 years old and approximately 90 percent of patients with CLL are estimated to be over the age of 55. The majority of patients with CLL have at least one comorbidity such as hypertension, diabetes, cardiovascular disease or COPD.
In the randomized, open-label, parallel-arm, pivotal Phase 3 COMPLEMENT 1 study, ofatumumab in combination with the oral chemotherapeutic agent chlorambucil versus chlorambucil alone was evaluated in 447 patients with CLL who were previously untreated and for whom fludarabine-based therapy was considered inappropriate by study investigators. Among the 447 patients (median age was 69 years) included in the study, the majority of patients (72 percent) had 2 or more comorbidities. The primary objective efficacy measure was PFS as assessed by a blinded Independent Review Committee using the International Workshop for Chronic Lymphocytic Leukemia updated National Cancer Institute-sponsored Working Group guidelines. Secondary efficacy endpoints included overall response, complete response and duration of response—those response rates were also assessed by an IRC.
With the exception of neutropenia and leukopenia, the overall rate of non-infusion-related Grade 3 or greater reactions with ofatumumab in combination with chlorambucil was similar to chlorambucil alone.
Arzerra is also indicated as monotherapy for the treatment of patients with CLL refractory to fludarabine and alemtuzumab.
Genmab is a publicly traded, international biotechnology company specializing in the creation and development of differentiated human antibody therapeutics for the treatment of cancer. Founded in 1999, the company's first marketed antibody, ofatumumab (Arzerra), was approved to treat CLL in patients who are refractory to fludarabine and alemtuzumab after less than eight years in development. Genmab's validated and next generation antibody technologies are expected to provide a steady stream of future product candidates. Partnering of innovative product candidates and technologies is a key focus of Genmab's strategy and the company has alliances with top-tier pharmaceutical and biotechnology companies.
