|By PR Newswire||
|April 17, 2014 05:25 PM EDT||
LONDON, April 17, 2014 /PRNewswire/ -- GlaxoSmithKline plc (LSE: GSK) and Genmab A/S (OMX: GEN) announced today that the U.S. Food and Drug Administration (FDA) has approved a Supplemental Biologic License Application (sBLA) for the use of Arzerra® (ofatumumab), a CD20-directed cytolytic monoclonal antibody, in combination with chlorambucil for the treatment of previously untreated patients with chronic lymphocytic leukaemia (CLL) for whom fludarabine-based therapy is considered inappropriate.1
The FDA approval of the first-line indication is based on results from a Phase III 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.1
"CLL is the most common form of leukaemia amongst 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., Chief Executive Officer of Genmab.
The results from COMPLEMENT 1, the randomised, open-label, parallel-arm, pivotal Phase III study evaluating the combination of ofatumumab and chlorambucil (N=221) versus chlorambucil alone (N=226) demonstrated statistically significant improvement in median PFS in patients randomised to ofatumumab and chlorambucil compared to patients randomised to chlorambucil alone (22.4 months versus 13.1 months, respectively) (HR=0.57 [95 per cent CI, 0.45, 0.72] p<0.001).1
The majority of adverse reactions (ARs) were Grade 2 or lower in both treatment arms. The most common (>/=5 per cent in the ofatumumab plus chlorambucil arm and also >/=2 per cent more than in the chlorambucil monotherapy arm) non-infusion-related ARs (all grades) as reported by investigators within 60 days following the last treatment were neutropaenia (27 per cent ofatumumab + chlorambucil, 18 per cent chlorambucil), asthaenia (8 per cent, 5 per cent), headache (7 per cent, 3 per cent), leukopaenia (6 per cent, 2 per cent), herpes simplex (6 per cent, 4 per cent), lower respiratory tract infection (5 per cent, 3 per cent), arthralgia (5 per cent, 3 per cent), and upper abdominal pain (5 per cent, 3 per cent).1
Infusion reactions (IRs) were seen in 67 per cent of patients in the ofatumumab plus chlorambucil arm. Ten per cent of IRs were Grade 3 or greater. IRs 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.1
CLL, the most commonly diagnosed adult leukaemia in Western countries,2, 3 accounts for approximately one-third of all cases of leukaemia.4 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.4, 5 The average age of diagnosis is 72 years old,4 and approximately 90 per cent of patients with CLL are estimated to be over the age of 55.6 The majority of patients with CLL have at least one comorbidity such as hypertension, diabetes, cardiovascular disease, or COPD.7
About COMPLEMENT 1
In the randomised, open-label, parallel-arm, pivotal Phase III 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.1 Among the 447 patients (median age was 69 years) included in the study, the majority of patients (72 per cent) had 2 or more comorbidities.1
The primary objective efficacy measure was PFS as assessed by a blinded Independent Review Committee (IRC) using the International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines (2008).1 Secondary efficacy endpoints included overall response (OR), complete response (CR), and duration of response.1 The OR and CR rates were also assessed by an IRC.1
With the exception of neutropaenia and leukopaenia, the overall rate of non-infusion-related Grade 3 or greater reactions with ofatumumab in combination with chlorambucil was similar to chlorambucil alone.1
Important Safety Information
The following Important Safety Information is based on the Highlights section of the Prescribing Information for Arzerra. Please consult the full prescribing information for all the labelled safety information for Arzerra.
WARNING: HEPATITIS B VIRUS REACTIVATION AND PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY1
Arzerra can cause serious, including fatal, infusion reactions manifesting as bronchospasm, dyspnoea, laryngeal oedema, pulmonary oedema, flushing, hypertension, hypotension, syncope, cardiac events (e.g., myocardial ischemia/infarction, acute coronary syndrome, arrhythmia, bradycardia), back pain, abdominal pain, pyrexia, rash, urticaria, angioedema, cytokine release syndrome, and anaphylactoid/anaphylactic reactions. Infusion reactions occur more frequently with the first two infusions. These reactions may result in temporary interruption or withdrawal of treatment.
Hepatitis B Virus Reactivation1
Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, has occurred in patients treated with Arzerra. Cases have been reported in patients who are hepatitis B surface antigen (HBsAg) positive and also in patients who are HBsAg negative but are hepatitis B core antibody (anti- HBc) positive. Reactivation also has occurred in patients who appear to have resolved hepatitis B infection (i.e., HBsAg negative, anti-HBc positive, and hepatitis B surface antibody [anti-HBs] positive).
HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive. Reactivation of HBV replication is often followed by hepatitis, i.e., increase in transaminase levels and, in severe cases, increase in bilirubin levels, liver failure, and death.
Hepatitis B Virus Infection1
Fatal infection due to hepatitis B in patients who have not been previously infected has been observed with Arzerra. Patients should be monitored for clinical and laboratory signs of hepatitis.
Progressive Multifocal Leukoencephalopathy1
Progressive multifocal leukoencephalopathy (PML) resulting in death has occurred with Arzerra. If PML is suspected, Arzerra should be discontinued and initiate evaluation for PML, including neurology consultation.
Tumour Lysis Syndrome1
Tumour lysis syndrome (TLS), including the need for hospitalisation, has occurred in patients treated with Arzerra. Patients with high tumour burden and/or high circulating lymphocyte counts (>25 x 109/L) are at greater risk for developing TLS. Consider tumour lysis prophylaxis with anti-hyperuricemics and hydration beginning 12 to 24 hours prior to infusion of Arzerra. For treatment of TLS, administer aggressive intravenous hydration and anti-hyperuricemic agents, correct electrolyte abnormalities, and monitor renal function.
Severe cytopaenias, including neutropaenia, thrombocytopaenia, and anaemia, can occur with Arzerra. Pancytopaenia, agranulocytosis, and fatal neutropaenic sepsis have occurred in patients who received Arzerra in combination with chlorambucil. Grade 3 or 4 late-onset neutropaenia (onset at least 42 days after last treatment dose) and/or prolonged neutropaenia (not resolved between 24 and 42 days after last treatment dose) were reported in patients who received Arzerra. Monitor complete blood counts at regular intervals during and after conclusion of therapy, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopaenias.
The safety of immunisation with live viral vaccines during or following administration of Arzerra has not been studied. The ability to generate an immune response to any vaccine following administration of Arzerra has not been studied.
Most Common Serious Adverse Reactions1
The following most common serious adverse reactions are discussed in greater detail above and in sections of the labelling: infusion reactions, hepatitis B virus reactivation, hepatitis B virus infection, progressive multifocal leukoencephalopathy, tumour lysis syndrome, cytopaenias.
Most Common Adverse Reactions1
The most common adverse reactions (>/=10%) seen in previously untreated CLL patients were infusion reactions and neutropaenia.
The revised full U.S. Prescribing Information, including Boxed Warning, will be available soon at https://www.gsksource.com/gskprm/htdocs/documents/ARZERRA.PDF. Prior to the revised label being posted online, a copy of the label may be requested from one of the GSK Media or Investor Relations contacts listed in the "GSK enquiries" section at the end of this document.
U.S. journalists, please click here for the U.S. electronic press kit: http://us.gsk.com/html/media-news/arzerra-press-kit.html.
About Arzerra (ofatumumab)
Arzerra (ofatumumab) is a CD20-directed monoclonal antibody indicated in combination with chlorambucil for the treatment of previously untreated patients with chronic lymphocytic leukaemia (CLL) for whom fludarabine-based therapy is considered inappropriate.1
Arzerra is also indicated as monotherapy for the treatment of patients with CLL refractory to fludarabine and alemtuzumab.1
Ofatumumab 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.
About GSK Patient Assistance Programmes
GSK has a number of patient assistance programmes for eligible patients in the United States who need help affording their medicines and vaccines. Patients who qualify for the programmes may benefit from GSK's Commitment to Access programme for oncology and specialty medicines which offers services and programmes including co-pay assistance in addition to traditional patient assistance support. For more information, patients in the United States can call 1-8ONCOLOGY1 (1-866-265-6491).
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 specialising 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 chronic lymphocytic leukaemia 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. For more information, visit www.genmab.com.
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™ and UniBody®.
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.
Registered in England & Wales:
980 Great West Road
1 GlaxoSmithKline. ARZERRA Prescribing Information 2014.
2 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.
3 Leukemia & Lymphoma Society. Chronic Lymphocytic Leukemia. http://www.lls.org/#/diseaseinformation/leukemia/chroniclymphocyticleuke.... Accessed January 3, 2014.
4 American Cancer Society. What are the key statistics for chronic lymphocytic leukemia? http://www.cancer.org/cancer/leukemia-chroniclymphocyticcll/detailedguide/leukemia-chronic-lymphocytic-key-statistics. Accessed January 3, 2014.
5 Leukemia & Lymphoma Society. The CLL Guide. http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/leukemia/pdf/cllguide.pdf. Accessed January 3, 2014.
6 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/suppl_6/vi50.full. Accessed January 3, 2014.
7 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.
With so much going on in this space you could be forgiven for thinking you were always working with yesterday’s technologies. So much change, so quickly. What do you do if you have to build a solution from the ground up that is expected to live in the field for at least 5-10 years? This is the challenge we faced when we looked to refresh our existing 10-year-old custom hardware stack to measure the fullness of trash cans and compactors.
Aug. 31, 2016 02:45 AM EDT Reads: 1,886
The emerging Internet of Everything creates tremendous new opportunities for customer engagement and business model innovation. However, enterprises must overcome a number of critical challenges to bring these new solutions to market. In his session at @ThingsExpo, Michael Martin, CTO/CIO at nfrastructure, outlined these key challenges and recommended approaches for overcoming them to achieve speed and agility in the design, development and implementation of Internet of Everything solutions wi...
Aug. 31, 2016 02:15 AM EDT Reads: 2,275
Today we can collect lots and lots of performance data. We build beautiful dashboards and even have fancy query languages to access and transform the data. Still performance data is a secret language only a couple of people understand. The more business becomes digital the more stakeholders are interested in this data including how it relates to business. Some of these people have never used a monitoring tool before. They have a question on their mind like “How is my application doing” but no id...
Aug. 31, 2016 02:00 AM EDT Reads: 1,988
Cloud computing is being adopted in one form or another by 94% of enterprises today. Tens of billions of new devices are being connected to The Internet of Things. And Big Data is driving this bus. An exponential increase is expected in the amount of information being processed, managed, analyzed, and acted upon by enterprise IT. This amazing is not part of some distant future - it is happening today. One report shows a 650% increase in enterprise data by 2020. Other estimates are even higher....
Aug. 31, 2016 01:45 AM EDT Reads: 3,079
Smart Cities are here to stay, but for their promise to be delivered, the data they produce must not be put in new siloes. In his session at @ThingsExpo, Mathias Herberts, Co-founder and CTO of Cityzen Data, will deep dive into best practices that will ensure a successful smart city journey.
Aug. 31, 2016 01:00 AM EDT Reads: 1,705
Identity is in everything and customers are looking to their providers to ensure the security of their identities, transactions and data. With the increased reliance on cloud-based services, service providers must build security and trust into their offerings, adding value to customers and improving the user experience. Making identity, security and privacy easy for customers provides a unique advantage over the competition.
Aug. 30, 2016 08:15 PM EDT Reads: 2,492
SYS-CON Events announced today that 910Telecom will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Housed in the classic Denver Gas & Electric Building, 910 15th St., 910Telecom is a carrier-neutral telecom hotel located in the heart of Denver. Adjacent to CenturyLink, AT&T, and Denver Main, 910Telecom offers connectivity to all major carriers, Internet service providers, Internet backbones and ...
Aug. 30, 2016 08:00 PM EDT Reads: 2,036
Qosmos has announced new milestones in the detection of encrypted traffic and in protocol signature coverage. Qosmos latest software can accurately classify traffic encrypted with SSL/TLS (e.g., Google, Facebook, WhatsApp), P2P traffic (e.g., BitTorrent, MuTorrent, Vuze), and Skype, while preserving the privacy of communication content. These new classification techniques mean that traffic optimization, policy enforcement, and user experience are largely unaffected by encryption. In respect wit...
Aug. 30, 2016 08:00 PM EDT Reads: 1,930
SYS-CON Events announced today that Pulzze Systems will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Pulzze Systems, Inc. provides infrastructure products for the Internet of Things to enable any connected device and system to carry out matched operations without programming. For more information, visit http://www.pulzzesystems.com.
Aug. 30, 2016 07:15 PM EDT Reads: 382
There is growing need for data-driven applications and the need for digital platforms to build these apps. In his session at 19th Cloud Expo, Muddu Sudhakar, VP and GM of Security & IoT at Splunk, will cover different PaaS solutions and Big Data platforms that are available to build applications. In addition, AI and machine learning are creating new requirements that developers need in the building of next-gen apps. The next-generation digital platforms have some of the past platform needs a...
Aug. 30, 2016 07:00 PM EDT Reads: 938
Data is an unusual currency; it is not restricted by the same transactional limitations as money or people. In fact, the more that you leverage your data across multiple business use cases, the more valuable it becomes to the organization. And the same can be said about the organization’s analytics. In his session at 19th Cloud Expo, Bill Schmarzo, CTO for the Big Data Practice at EMC, will introduce a methodology for capturing, enriching and sharing data (and analytics) across the organizati...
Aug. 30, 2016 06:15 PM EDT Reads: 381
DevOps at Cloud Expo – being held November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA – announces that its Call for Papers is open. Born out of proven success in agile development, cloud computing, and process automation, DevOps is a macro trend you cannot afford to miss. From showcase success stories from early adopters and web-scale businesses, DevOps is expanding to organizations of all sizes, including the world's largest enterprises – and delivering real results. Am...
Aug. 30, 2016 05:45 PM EDT Reads: 3,596
Traditional on-premises data centers have long been the domain of modern data platforms like Apache Hadoop, meaning companies who build their business on public cloud were challenged to run Big Data processing and analytics at scale. But recent advancements in Hadoop performance, security, and most importantly cloud-native integrations, are giving organizations the ability to truly gain value from all their data. In his session at 19th Cloud Expo, David Tishgart, Director of Product Marketing ...
Aug. 30, 2016 05:00 PM EDT Reads: 907
Fact: storage performance problems have only gotten more complicated, as applications not only have become largely virtualized, but also have moved to cloud-based infrastructures. Storage performance in virtualized environments isn’t just about IOPS anymore. Instead, you need to guarantee performance for individual VMs, helping applications maintain performance as the number of VMs continues to go up in real time. In his session at Cloud Expo, Dhiraj Sehgal, Product and Marketing at Tintri, wil...
Aug. 30, 2016 04:15 PM EDT Reads: 978
Internet of @ThingsExpo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, is co-located with 19th Cloud Expo and will feature technical sessions from a rock star conference faculty and the leading industry players in the world. The Internet of Things (IoT) is the most profound change in personal and enterprise IT since the creation of the Worldwide Web more than 20 years ago. All major researchers estimate there will be tens of billions devices - comp...
Aug. 30, 2016 03:30 PM EDT Reads: 3,785