Company Announcement
- Interim analysis of PROLONG study met primary endpoint
- Further analysis of safety and efficacy data underway
- Interim analysis to be shared with regulatory agencies to evaluate the potential for future regulatory filings
Copenhagen, Denmark; July 31, 2014 - GlaxoSmithKline plc (LSE/NYSE: GSK) and Genmab A/S (OMX: GEN) announced today that an Independent Data Monitoring Committee (IDMC) interim analysis of a Phase III study, PROLONG (OMB 112517), reached the predefined significance level for efficacy (p≤0.001). The interim analysis demonstrated that treatment with ofatumumab (Arzerra™) met the primary endpoint of improving progression free survival (PFS). The study evaluated ofatumumab maintenance therapy versus no further treatment (observation) in patients with relapsed chronic lymphocytic leukemia (CLL) who responded to treatment at relapse.
The IDMC did not identify any new safety signals and will continue to monitor patients for safety until all study patients complete therapy. Further analysis of the safety and efficacy data is underway and will be shared with regulators and the scientific community in the coming months.
“This interim result from the PROLONG study demonstrated that maintenance therapy with ofatumumab lowered the risk of disease progression in patients who responded to treatment at relapse. We look forward to sharing the results of the interim analysis with regulatory agencies to evaluate the potential for future regulatory filings,” said Dr. Rafael Amado, Head of Oncology R&D, GSK.
“We are very pleased that this study of ofatumumab, the first Phase III study to evaluate maintenance therapy for relapsed CLL, met the primary endpoint at the interim analysis. This result indicates the potential of ofatumumab in this setting where there are currently no approved treatments. We look forward to presenting the detailed data from this study at a future medical conference,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.
About PROLONG
This pivotal Phase III study was designed to randomize up to 532 patients with relapsed CLL who have responded to treatment at relapse, to either ofatumumab maintenance treatment or no further treatment (observation). Patients in the ofatumumab arm receive an initial dose of 300 mg of ofatumumab, followed one week later by a second dose of 1,000 mg, then doses of 1,000 mg every 8 weeks for up to two years, while patients in the observation treatment arm receive no further treatment.
The primary endpoint of the study is PFS. Secondary objectives will evaluate clinical benefit, safety, tolerability, the health-related quality of life of subjects treated with ofatumumab versus no further treatment, and pharmacokinetics among relapsed CLL patients receiving maintenance therapy with ofatumumab.
About CLL
CLL, the most commonly diagnosed adult leukaemia in western countries, accounts for approximately one-third of all cases of leukemia. 1,2,3 In the USA, 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. 3,4 The average age of diagnosis is 72 years, and approximately 90 percent of patients with CLL are estimated to be over the age of 55 years. 3,5 The majority of patients with CLL have at least one comorbidity such as hypertension, diabetes, cardiovascular disease, or COPD. 6
About ofatumumab (Arzerra)
Ofatumumab—a monoclonal antibody that is designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes—is not approved or licensed anywhere in the world as maintenance treatment for relapsed CLL.
In the USA, ofatumumab is approved for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. In the EU, ofatumumab is approved for use in combination with chlorambucil or bendamustine for the treatment of patients with CLL who have not received prior therapy and who are not eligible for fludarabine-based therapy. Ofatumumab is also approved for first-line use in Russia.
In more than 50 countries worldwide, ofatumumab is indicated as monotherapy for the treatment of patients with CLL refractory to fludarabine and alemtuzumab.
Ofatumumab is being developed under a co-development and collaboration agreement between Genmab and GSK.
Arzerra is a trademark of the GSK group of companies.
Important Safety Information for ofatumumab (Arzerra)
The overall safety profile of ofatumumab in CLL (previously untreated and relapsed or refractory) is based on data from more than 500 patients treated alone or in combination with other therapies in clinical trials.
The most common undesirable effects for ofatumumab include adverse events associated with infusion reactions, cytopenias (neutropenia, anemia, febrile neutropenia, thrombocytopenia, leukopenia) and infections (lower respiratory tract infection, including pneumonia, upper respiratory tract infection, sepsis, including neutropenic sepsis and septic shock, herpes virus infection, urinary tract infection).
Contraindications:
Hypersensitivity to ofatumumab or to any of the excipients.
Special warnings and precautions for use of ofatumumab are summarized as follows:
Infusion reactions
Ofatumumab has been associated with infusion reactions. These reactions may result in temporary interruption or withdrawal of treatment or death. Pre-medications attenuate infusion reactions but these may still occur, predominantly during the first infusion. Infusion reactions may include, but are not limited to, anaphylactic reactions, bronchospasm, cardiac events (eg myocardial ischemia / infarction, bradycardia ), chills/rigors, cough, cytokine release syndrome, diarrhea , dyspnoea, fatigue, flushing, hypertension, hypotension, nausea, pain, pulmonary edema , pruritus, pyrexia, rash, and urticaria. Even with pre-medication, severe reactions, including cytokine release syndrome, have been reported following ofatumumab use. In cases of severe infusion reaction, the infusion of ofatumumab must be interrupted immediately and symptomatic treatment instituted (see Dosage and Administration for changes to infusion rates following infusion reactions).
Infusion reactions occur more frequently on the first day of infusion and tend to decrease with subsequent infusions. Patients with a history of decreased pulmonary function may be at a greater risk for pulmonary complications from severe reactions and should be monitored closely during infusion of ofatumumab.
Tumor lysis syndrome
In patients with CLL, tumor lysis syndrome (TLS) may occur with use of ofatumumab. Risk factors for TLS include a high tumor burden, high concentrations of circulating cells (≥ 25,000/mm 3 ), hypovolemia, renal insufficiency, elevated pre-treatment uric acid levels and elevated lactate dehydrogenase levels. Management of TLS includes correction of electrolyte abnormalities, monitoring of renal function, maintenance of fluid balance and supportive care.
Progressive multifocal leukoencephalopathy
Progressive multifocal leukoencephalopathy (PML) and death has been reported in CLL patients receiving cytotoxic pharmacotherapy, including ofatumumab. If a diagnosis of PML is suspected, ofatumumab should be discontinued and referral to a neurologist should be considered.
Immunizations
The safety of, and ability to generate a primary or anamnestic response to, immunization with live attenuated or inactivated vaccines during treatment with ofatumumab has not been studied.
Hepatitis B
Hepatitis B virus (HBV) infection and reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, has occurred in patients treated with drugs classified as CD20-directed cytolytic antibodies, including ofatumumab. All patients should be screened for HBV infection before initiation of ofatumumab treatment, patients previously exposed to HBV should be followed closely in consultation with an expert in this disease. Patients with evidence of prior HBV infection should be monitored for clinical and laboratory signs of hepatitis or HBV reactivation.
Cardiovascular
Patients with a history of cardiac disease should be monitored closely. Ofatumumab should be discontinued in patients who experience serious or life-threatening cardiac arrhythmias.
The effect of multiple doses of ofatumumab on the QTc interval was evaluated in a pooled analysis of three open-label studies in patients with CLL (N=85). Increases above 5 msec were observed in the median/mean QT/QTc intervals in the pooled analysis. No large changes in the mean QTc interval (ie, >20 milliseconds) were detected.
Bowel obstruction
Bowel obstruction has been reported in patients receiving anti-CD20 monoclonal antibody therapy, including ofatumumab. Patients who present with abdominal pain, especially early in the course of ofatumumab therapy, should be evaluated and appropriate treatment instituted.
For the full US Prescribing Information, including Boxed Warning, visit https://www.gsksource.com/gskprm/htdocs/docum...RZERRA.PDF . F or the full EU Summary of Product Characteristics (SPC) visit http://health.gsk.com/ .
GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com .
About Genmab A/S
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 currently has one marketed antibody, Arzerra™ (ofatumumab) for the treatment of certain chronic lymphocytic leukemia indications, a clinical pipeline with both late and early stage programs, and an innovative pre-clinical pipeline. Genmab's technology base consists of validated and proprietary next generation antibody technologies - the DuoBody® platform for generation of bispecific antibodies, and the HexaBody™ platform which creates effector function enhanced antibodies. Genmab's deep antibody expertise is expected to provide a stream of future product candidates. Partnering of selected 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. For more information visit www.genmab.com .
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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2013.
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Forward Looking Statement for Genmab
This Company Announcement contains forward looking statements. The words “believe”, “expect”, “anticipate”, “intend” and “plan” and similar expressions identify forward looking statements. Actual results or performance may differ materially from any future results or performance expressed or implied by such statements. The important factors that could cause our actual results or performance to differ materially include, among others, risks associated with pre-clinical and clinical development of products, uncertainties related to the outcome and conduct of clinical trials including unforeseen safety issues, uncertainties related to product manufacturing, the lack of market acceptance of our products, our inability to manage growth, the competitive environment in relation to our business area and markets, our inability to attract and retain suitably qualified personnel, the unenforceability or lack of protection of our patents and proprietary rights, our relationships with affiliated entities, changes and developments in technology which may render our products obsolete, and other factors. For a further discussion of these risks, please refer to the risk management sections in Genmab’s most recent financial reports, which are available on www.genmab.com . Genmab does not undertake any obligation to update or revise forward looking statements in this Company Announcement nor to confirm such statements in relation to actual results, unless required by law.
Genmab A/S and its subsidiaries own the following trademarks: Genmab ® ; the Y-shaped Genmab logo ® ; Genmab in combination with the Y-shaped Genmab logo™; the DuoBody logo™; the HexaBody logo™; HuMax ® ; HuMax-CD20 ® ; DuoBody ® ; HexaBody™ and UniBody ® .
1 Wadhwa P, Morrison VA. Infectious complications of chronic lymphocytic leukemia. Seminars in Oncology. 2006;33:240-249. http://www.cllsupport.org.uk/infections.pdf. Accessed February 12, 2014.
2 Leukemia & Lymphoma Society. Chronic Lymphocytic Leukemia. http://www.lls.org/#/diseaseinformation/leuke...cleukemia/. Accessed January 3, 2014.
3 American Cancer Society. What are the key statistics for chronic lymphocytic leukemia? http://www.cancer.org/cancer/leukemia-chronic...statistics. Accessed January 3, 2014.
4 Leukemia & Lymphoma Society. The CLL Guide. http://www.lls.org/content/nationalcontent/re...lguide.pdf. Accessed January 3, 2014.
5 Eichhorst B, Hallek M, Dreyling M. Chronic lymphocytic leukemia: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2011;22 Suppl 2, 50-54. http://annonc.oxfordjournals.org/content/22/s.../vi50.full. Accessed January 3, 2014.
6 Shanafelt, TD, et al. Quality of life in chronic lymphocytic leukemia: an international survey of 1482 patients. British Journal of Hematology. 2007;139, 255-264.
Company Announcement no. 38
CVR no. 2102 3884
Genmab A/S
Bredgade 34E
1260 Copenhagen K
Denmark
