GSK and Genmab receive FDA approval for Arzerra® (ofatumumab)

Issued: London UK

GlaxoSmithKline plc (LSE: GSK) and Genmab A/S (OMX: GEN) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending a variation to the terms of the marketing authorisation for Arzerra™ (ofatumumab) for a new indication in combination with chlorambucil or bendamustine for the treatment of patients with chronic lymphocytic leukaemia (CLL) who have not received prior therapy and who are not eligible for fludarabine-based therapy.¹

“This CHMP opinion for Arzerra in the first-line setting brings GSK one step closer to offering a new treatment option for patients with previously untreated CLL in Europe.” said Dr Rafael Amado, Head of Oncology R&D at GSK.  

“We are pleased to receive the positive opinion from the CHMP for Arzerra in combination with chlorambucil or bendamustine for first line CLL and look forward to a final decision from the European Commission in the next few months,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The CHMP recommendation of the first-line indication is based on results from two trials in patients with previously untreated CLL considered inappropriate for a fludarabine-based treatment:

• Phase III OMB110911 study (COMPLEMENT 1), a randomised, open-label, parallel-arm, multicentre, pivotal Phase III study evaluating the combination of ofatumumab and chlorambucil (N=221) versus chlorambucil alone (N=226)¹
• Phase II OMB115991, a single-arm, multicentre study that evaluated the efficacy of ofatumumab in combination with bendamustine (N= 44)²

A CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission (EC),³ but does not always result in marketing authorisation. A final decision by the EC is anticipated during the third quarter of 2014.

About Arzerra (ofatumumab)

Arzerra (ofatumumab) is a monoclonal antibody that is designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes.¹

In the US, Arzerra^® is approved (April 2014) for use in combination with chlorambucil for the treatment of previously untreated patients with CLL for whom fludarabine-based therapy is considered inappropriate. For full US prescribing information, including Boxed Warning, please seehttps://www.gsksource.com/gskprm/htdocs/documents/ARZERRA.PDF

Arzerra is also approved for first-line use in Russia.

In more than 50 countries worldwide, Arzerra is indicated as monotherapy for the treatment of patients with CLL refractory to fludarabine and alemtuzumab.

Arzerra is being developed under a co-development and collaboration agreement between Genmab and GSK.

Arzerra is a registered trademark of the GSK group of companies.

Safety information for Arzerra (ofatumumab)

Please consult the full Summary of Product Characteristics for all the labelled safety information for Arzerra.

Contraindications:

Hypersensitivity to ofatumumab or to any of the excipients.¹

Special warnings and precautions for use of Arzerra (ofatumumab) include:

Infusion reactions¹

Ofatumumab has been associated with infusion reactions leading to temporary interruption of treatment or withdrawal of treatment.  Infusion reactions may include anaphylactoid events, cardiac events, chills/rigors, cough, cytokine release syndrome, diarrhoea, dyspnoea, fatigue, flushing, hypertension, hypotension, nausea, pain, pyrexia, rash, and urticaria.  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.

Tumour lysis syndrome¹

In patients with CLL, tumour lysis syndrome (TLS) may occur with use of ofatumumab.  Risk factors for TLS include a high tumour burden, high concentrations of circulating cells (≥ 25,000/mm³), hypovolaemia, 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 leukoencephalopathy¹

Progressive multifocal leukoencephalopathy (PML) and death has been reported in CLL patients receiving cytotoxic pharmacotherapy, including ofatumumab.  If a diagnosis of PML is suspected Arzerra should be discontinued and referral to a neurologist should be considered.

Immunisations¹

The safety of, and ability to generate a primary or anamnestic response to, immunisation with live attenuated or inactivated vaccines during treatment with ofatumumab has not been studied. 

Hepatitis B¹

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.

Cardiovascular¹

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 (i.e., >20 milliseconds) were detected. 

Bowel obstruction¹

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.

Laboratory monitoring¹

Cytopenias, including prolonged and late-onset neutropenia, have been reported during ofatumumab therapy.  Complete blood counts, including neutrophil and platelet counts should be obtained at regular intervals during ofatumumab therapy and more frequently in patients who develop cytopenias.

Sodium content¹

This medicinal product contains 34.8 mg sodium per 300 mg dose, 116 mg sodium per 1,000 mg dose and 232 mg sodium per 2,000 mg dose.  This should be taken into consideration by patients on a controlled sodium diet.

The most common undesirable effects for ofatumumab include adverse events associated with infusion reactions, cytopenias (neutropenia, anaemia, febrile neutropenia, thrombocytopaenia, leucopenia 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).¹

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 preclinical 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 http://www.genmab.com/.

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.

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^®; the DuoBody™ logo; the Hexabody logo™; HuMax^®; HuMax-CD20^®; DuoBody^®, HexaBody^TM and UniBody^®.

References

1. GlaxoSmithKline Clinical Study Register. Study OMB110911. www.gsk-clinicalstudyregister.com/study/OMB110911?study_ids=OMB110911#ps. Accessed 19 May 2014.
2. GlaxoSmithKline Clinical Study Register. Study 115991 www.gsk-clinicalstudyregister.com/study/115991?study_ids=omb115991#ps. Accessed 19 May 2014.
3. European Commission. The Centralised Procedure. http://ec.europa.eu/health/authorisation-procedures-centralised_en.htm.%20Accessed%2014%20May%202014.