LONDON & ROCKVILLE, Md.—Marking the first time in more than 50 years that we've seen a new approved drug for systemic lupus, the U.S. Food and Drug Administration (FDA) decided March 9 to issue approval for Benlysta (belimumab) from GlaxoSmithKline plc (GSK) and Human Genome Sciences Inc. (HGS) for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy. The drug is expected to be available to physicians and patients before the end of March.
"The approval of Benlysta is an important step for appropriate lupus patients," says Dr. Moncef Slaoui, head of research and development for GSK, saying he looks forward to further working with HGS to bring this new medicine to patients in the United States. "Patients have been waiting for new treatment options to help manage this chronic disease," he adds.
"We expect to have this novel therapy available to physicians and patients within about two weeks, and our entire organization looks forward to the positive impact we hope this new therapy will have for patients with systemic lupus," says H. Thomas Watkins, president and CEO of HGS.
Of course, you'd expect that such big news would have a "but" (or a few of them) attached to it, and the U.S. label required by the FDA does include the following limitations of use: The efficacy of belimumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus, and has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of belimumab is therefore not recommended in these situations.
Also, the FDA noted that black patients "did not appear to respond to treatment" with Benlysta in clinical trials but added that studies "lacked sufficient numbers to establish a definite conclusion." In the end, the FDA chose not to warn against use in black patients—which caused many investors to breathe a huge sigh of relief—and only required that GSK and HGS run a post-approval study with black patients.
In addition, among the potential side effects of using the drug, GSK and HGS note that serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including belimumab. Also, they note, the impact of treatment with belimumab on the development of malignancies is not known and, as with other immunomodulating agents, the mechanism of action of belimumab could increase the risk for developing malignancies.
Even with such caveats, Thomson Reuters consensus forecasts predict that Benlysta's annual global sales may hit or exceed $3 billion by 2015, and some analysts predict sales as high as $5 billion in later years.
"Benlysta's approval will send shockwaves through the lupus community as lupus has been a clinical and commercial minefield historically," asserts James Wentworth, a healthcare analyst at independent market analysis firm Datamonitor. "Other companies will now be spurred on to continue development of additional lupus drugs, especially those with the same mechanism as Benlysta. With a fairly wide label, Benlysta will help to make lupus the next billion-dollar autoimmune market."
Current treatment for lupus, Wentworth, is dictated by organ involvement and severity and is largely treated by off-label medications such as the immunosuppressant CellCept and the CD20 MAb Rituxan, as well as corticosteroids and anti-malarial agents, such as hydroxychloroquine.
"Human Genome Sciences and GlaxoSmithKline will begin marketing Benlysta in the U.S., with a commercial launch by the end of March," Wentworth says. "In the EU, Benlysta is expected to receive approval from the European Medicines Agency (EMA) later in 2011, but this presents a lower commercial opportunity due to the smaller population size in the five major EU markets (France, Germany, Italy, Spain and the UK)."
Reportedly, HGS has been building up an inventory of the drug sufficient for about a year and enough for approximately 50,000 patients. While the market price for Benlysta is not yet known, market watchers expect it to be in the realm of $30,000 per patient, based on therapies used in rheumatoid arthritis and multiple sclerosis.
"Moreover, HGS will adopt a three-pronged approach to help drive Benlysta's initial post-launch uptake," Wentworth says. "The company will target patients, rheumatologists and will also liaise with payers to help facilitate reimbursement, prior to receiving a J-code in 2012. Datamonitor expects Benlysta will remain the only marketed U.S. biologic for lupus for at least the next three years. However, there is competition looming with several Phase III agents in development, including UCB's epratuzumab, a CD22 MAb."
Other BlyS-targeted biologics in the late-stage lupus pipeline will be encouraged by Benlysta's approval, Wentworth notes, adding: "In Q1 2011, Eli Lilly commenced almost identical Phase III trials to Benlysta's for its BlyS MAb LY2127399, in the absence of any Phase II data. Eli Lilly is also using the SLE Responder Index that HGS Sciences developed for Benlysta."
HGS and GSK are developing Benlysta under a definitive co-development and co-commercialization agreement entered into in 2006, under which HGS had responsibility for conducting the belimumab Phase III trials, with assistance from GSK. The companies share equally in Phase III/IV development costs, sales and marketing expenses, and profits of any product commercialized under the current agreement.
But while GSK and HGS are the stars of the show, others have also wanted to note their part in helping to make such a historic drug possible. The Scripps Research Institute, for example, noted in a news release the day of Benlysta's approval that scientific advances within its walls were key to laying the foundation for the new drug, which represents the first in a new class of pharmaceuticals that prevents the body from attacking its own critical tissues.
"I am deeply gratified that our scientific findings have proven so valuable to drug discovery," said Dr. Richard A. Lerner in the official statement. "This development underlines the importance of basic academic science in laying important groundwork for life-saving medical advances."
Also, the Lupus Foundation of America (LFA) issued a news release the same day, with its president and CEO, Sandra C. Raymond, noting that the LFA is "partnering with key stakeholders from industry, government, and the scientific community to evaluate data from previous lupus clinical trials with the goal to improve the design of future studies."
"This is a historic day for the millions of people with lupus and their families around the world who have waited more than 52 years for a treatment breakthrough for lupus," Raymond also said. "We at the LFA applaud the FDA's decision to approve Benlysta. Benlysta is the first drug ever to be specifically developed to treat lupus, and is a significant first step toward reaching our goal of developing an arsenal of new, safe, effective, and tolerable treatments. Today marks the beginning of a new era of improved diagnosis, prevention, and treatment for the disease."
She also thanked the developers of the drug at Human Genome Sciences and GlaxoSmithKline, "who have long been committed to the research and development process," adding: "There are a number of pioneering biotechnology and pharmaceutical companies, involved in the research and development of new treatments for lupus, and our hope is that today's decision will further stimulate additional companies to invest in new therapies for lupus."
To that end, to help build on this momentum and encourage the development of new treatments, the LFA has launched new initiatives that help to strengthen clinical trials, Raymond says. These programs include the launch of a web-based program designed to train clinical investigators on the instruments used in trials and the creation of the LFA Lupus Research Registry, which enables individuals to be notified about new clinical trials in their geographic area.
"The approval of Benlysta is an important step for appropriate lupus patients," says Dr. Moncef Slaoui, head of research and development for GSK, saying he looks forward to further working with HGS to bring this new medicine to patients in the United States. "Patients have been waiting for new treatment options to help manage this chronic disease," he adds.
"We expect to have this novel therapy available to physicians and patients within about two weeks, and our entire organization looks forward to the positive impact we hope this new therapy will have for patients with systemic lupus," says H. Thomas Watkins, president and CEO of HGS.
Of course, you'd expect that such big news would have a "but" (or a few of them) attached to it, and the U.S. label required by the FDA does include the following limitations of use: The efficacy of belimumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus, and has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of belimumab is therefore not recommended in these situations.
Also, the FDA noted that black patients "did not appear to respond to treatment" with Benlysta in clinical trials but added that studies "lacked sufficient numbers to establish a definite conclusion." In the end, the FDA chose not to warn against use in black patients—which caused many investors to breathe a huge sigh of relief—and only required that GSK and HGS run a post-approval study with black patients.
In addition, among the potential side effects of using the drug, GSK and HGS note that serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including belimumab. Also, they note, the impact of treatment with belimumab on the development of malignancies is not known and, as with other immunomodulating agents, the mechanism of action of belimumab could increase the risk for developing malignancies.
Even with such caveats, Thomson Reuters consensus forecasts predict that Benlysta's annual global sales may hit or exceed $3 billion by 2015, and some analysts predict sales as high as $5 billion in later years.
"Benlysta's approval will send shockwaves through the lupus community as lupus has been a clinical and commercial minefield historically," asserts James Wentworth, a healthcare analyst at independent market analysis firm Datamonitor. "Other companies will now be spurred on to continue development of additional lupus drugs, especially those with the same mechanism as Benlysta. With a fairly wide label, Benlysta will help to make lupus the next billion-dollar autoimmune market."
Current treatment for lupus, Wentworth, is dictated by organ involvement and severity and is largely treated by off-label medications such as the immunosuppressant CellCept and the CD20 MAb Rituxan, as well as corticosteroids and anti-malarial agents, such as hydroxychloroquine.
"Human Genome Sciences and GlaxoSmithKline will begin marketing Benlysta in the U.S., with a commercial launch by the end of March," Wentworth says. "In the EU, Benlysta is expected to receive approval from the European Medicines Agency (EMA) later in 2011, but this presents a lower commercial opportunity due to the smaller population size in the five major EU markets (France, Germany, Italy, Spain and the UK)."
Reportedly, HGS has been building up an inventory of the drug sufficient for about a year and enough for approximately 50,000 patients. While the market price for Benlysta is not yet known, market watchers expect it to be in the realm of $30,000 per patient, based on therapies used in rheumatoid arthritis and multiple sclerosis.
"Moreover, HGS will adopt a three-pronged approach to help drive Benlysta's initial post-launch uptake," Wentworth says. "The company will target patients, rheumatologists and will also liaise with payers to help facilitate reimbursement, prior to receiving a J-code in 2012. Datamonitor expects Benlysta will remain the only marketed U.S. biologic for lupus for at least the next three years. However, there is competition looming with several Phase III agents in development, including UCB's epratuzumab, a CD22 MAb."
Other BlyS-targeted biologics in the late-stage lupus pipeline will be encouraged by Benlysta's approval, Wentworth notes, adding: "In Q1 2011, Eli Lilly commenced almost identical Phase III trials to Benlysta's for its BlyS MAb LY2127399, in the absence of any Phase II data. Eli Lilly is also using the SLE Responder Index that HGS Sciences developed for Benlysta."
HGS and GSK are developing Benlysta under a definitive co-development and co-commercialization agreement entered into in 2006, under which HGS had responsibility for conducting the belimumab Phase III trials, with assistance from GSK. The companies share equally in Phase III/IV development costs, sales and marketing expenses, and profits of any product commercialized under the current agreement.
But while GSK and HGS are the stars of the show, others have also wanted to note their part in helping to make such a historic drug possible. The Scripps Research Institute, for example, noted in a news release the day of Benlysta's approval that scientific advances within its walls were key to laying the foundation for the new drug, which represents the first in a new class of pharmaceuticals that prevents the body from attacking its own critical tissues.
"I am deeply gratified that our scientific findings have proven so valuable to drug discovery," said Dr. Richard A. Lerner in the official statement. "This development underlines the importance of basic academic science in laying important groundwork for life-saving medical advances."
Also, the Lupus Foundation of America (LFA) issued a news release the same day, with its president and CEO, Sandra C. Raymond, noting that the LFA is "partnering with key stakeholders from industry, government, and the scientific community to evaluate data from previous lupus clinical trials with the goal to improve the design of future studies."
"This is a historic day for the millions of people with lupus and their families around the world who have waited more than 52 years for a treatment breakthrough for lupus," Raymond also said. "We at the LFA applaud the FDA's decision to approve Benlysta. Benlysta is the first drug ever to be specifically developed to treat lupus, and is a significant first step toward reaching our goal of developing an arsenal of new, safe, effective, and tolerable treatments. Today marks the beginning of a new era of improved diagnosis, prevention, and treatment for the disease."
She also thanked the developers of the drug at Human Genome Sciences and GlaxoSmithKline, "who have long been committed to the research and development process," adding: "There are a number of pioneering biotechnology and pharmaceutical companies, involved in the research and development of new treatments for lupus, and our hope is that today's decision will further stimulate additional companies to invest in new therapies for lupus."
To that end, to help build on this momentum and encourage the development of new treatments, the LFA has launched new initiatives that help to strengthen clinical trials, Raymond says. These programs include the launch of a web-based program designed to train clinical investigators on the instruments used in trials and the creation of the LFA Lupus Research Registry, which enables individuals to be notified about new clinical trials in their geographic area.
