Today’s News
July 10, 2010: Snoop Dogg speaks about his daughter, Cori, who was diagnosed with lupus at age six. She is now doing well at age 13: http://www.ontheredcarpet.com/2010/07/snoop-dogg-says-daughter-winning-lupus-fight.html.
July 8, 2010: Benlysta success continues to build. Full results from the BLISS-76 study of Human Genome Science and GlaxoSmithKline’s lupus drug Benlysta (belimumab) suggest the drug is efficacious and has an encouraging safety profile, according to a presentation at EULAR, the European League Against Rheumatism. BLISS-76 was a 76-week, double-blind trial that compared the two doses versus placebo in 819 seropositive SLE patients and is one of two pivotal studies to evaluate the safety and efficacy of belimumab in SLE patients. Two doses were studied: 1 mg/kg and 10mg/kg administered intravenously once every four weeks. According to Prof van Vollenhoven, the treatment and placebo groups had similar adverse events, and efficacy was seen with the higher dose with the primary endpoint. Read more at: http://www.pharmatimes.com/worldnews/article.aspx?id=18065.
July 3, 2010: There is a wonderful advocacy group called the LUISA project in the Philippines. Lupus affects women of color more often than it affects caucasian women. This organization is extremely inspiring and relies on scientific symposiums for updates on lupus research and treatment. Manila is fortunate to boast such an active and progressive group of people. For the latest lupus research news and inspiration, see: http://www.luisaproject.org.
July 1, 2010: Terri Seymour, popular TV host, has lupus: http://www.fameblab.com/article/terri-seymour-admits-she-has-lupus-disease. It is always nice to see celebrities helping raise the profile of this illness by coming forward. Note: the most powerful advocacy we can do as patients is use our voice. Consider writing in to this website with your stories to: rmizuno@comcast.net, and joining in the fight on Capitol Hill with the Lupus Research Institute. These forums, wherein lupus patients advocate for funds for increasing doctor education about lupus, tend to have an outstanding effect. Over 1.5 million dollars has been raised through these efforts within a year and a half.
May 7, 2010: Julian Lennon sings for lupus Friday May 7 2010 – http://lupus.webmd.com/features/julian-lennon-sings-a-new-song-for-lupus?src=RSS_PUBLIC. Julian had been somewhat out of the limelight for quite some time until he became inspired by the memory of an old friend and a famous song. In 2009, Lennon met American singer/songwriter James Scott Cook through a mutual friend and offered to contribute background vocals on a song Cook was writing. But when he heard the tune, a tribute to Cook’s grandmother, Lucy, who had lupus, he felt compelled to do more. Last December, the upbeat pop single “Lucy” was released as an extended play CD. Lennon earmarked a portion of sales for lupus research, shared by the Lupus Foundation of America (LFA) and the St. Thomas’ Lupus Trust in Great Britain. This month Julian will sing “Lucy” at LFA’s Butterfly Gala National Awards Dinner in Washington, D.C. Come back here: www.beatlupus.com/news-on-lupus for all updates and daily news flashes.
May 6, 2010: Huge news. Urinary neutrophil gelatinase-associated lipocalin (NGAL) level may predict disease activity in adult patients with lupus nephritis. See: http://www.nature.com/nrneph/journal/v6/n5/full/nrneph.2010.49.html. This will go a long way in creating opportunity for life-saving treatment, as early diagnosis in lupus nephritis is key (and saved Regan’s life).
May 5, 2010: Regan is proud to be represented and supported by her parents and a ton of excited British Columbia residents for Lupus Canada. May is Lupus Awareness month. Let’s bind together and raise some research! See: http://www.bclocalnews.com/vancouver_island_north/comoxvalleyrecord/news/93035594.html.
May 4, 2010: The Lupus Foundation of Colorado’s annual Vines of Hope fundraiser was a resounding success. I got to speak and I really enjoyed that. It was an emotional, yet extremely positive and uplifting evening. The whole event resulted in great friendships, wonderful experiences, and a lot of fundraising for research! The research comprises local and national programs including the Lupus Research Institute, the United States’ largest private funder of novel lupus research. 70% of their funded scientists go on to receive millions in grant money from the National Institutes of Health. Also, the LFC funds local Denver doctors who work on biomarkers to identify lupus in its early stages. As you know, early diagnosis is the key to success. Way to go, LFC! I am happy to have been a part of this organization and event. Be sure to visit www.beatlupus.com/news-on-lupus for all updates and daily news flashes.
May 3, 2010: The S.L.E. Lupus Foundation—in its 40th year promoting lupus awareness, education, advocacy, and research—is launching National Lupus Awareness Month 2010 with a 115-sq-ft display window at 10 Rockefeller Plaza to educate young women about the disease. The window, viewed by thousands of visitors each day in the heart of New York City, was generously donated by EHE International for the month of May. For the full article see: http://www.prweb.com/releases/2010/05/prweb3949314.htm.
April 19, 2010: A conference dedicated to autoimmune issues, will be held on Sunday, May 2, in Scranton. These conferences are the keys to seeding novel research. Typically, novel research funded by organizations such as the Lupus Research Institute, goes on to obtain millions in funding from the National Institutes of Health. This will be a productive meeting working towards a cure for lupus. See: http://thetimes-tribune.com/news/if-you-go-conference-will-seek-to-unlock-mysteries-of-autoimmune-diseases-1.734810. Secondly: there is much research touting the benefits of fish oil for people with arthritis. I take it myself and have found it to ease pain and increase joint comfort, allowing me freedom of movement and the ability to exercise. See: http://www.livestrong.com/article/105190-fish-oil-lupus/. For all updates and daily news items, go to www.beatlupus.com/news-on-lupus.
April 18, 2010: The results are in: Myrtle Beach’s lupus walk held Saturday, April 17, was a resounding success. Over 200 people showed up to support lupus research. For more information on this inspiring group, see: http://www.wmbfnews.com/Global/story.asp?S=12329413.
April 16, 2010: A recently issued stockholder’s report from Human Genome Sciences, the co-makers (along with GlaxoSmithKline) of the highly anticipated lupus drug Benlysta, is out. It includes the story of a woman from Lakewood Colorado in their report, telling her story about lupus. Did you know that until a new drug becomes FDA approved, there currently is no dedicated drug for lupus? Patients use medications that were initially developed for other diseases – immune suppresants and anti-malarials. It is predicted that soon, Benlysta will become commercially available. See: www.beatlupus.com/articles.
April 10 2010: According to PRNewswire, Benlysta will garner sales of more than $500 Million in 2018 in the Systemic Lupus Erythematosus drug market.
Regulatory approval for the drug is expected in 2011 for the United States and Europe. When this happens, Human Genome Sciences/GlaxoSmithKline’s Benlysta will garner sales of more than $500 million in 2018 in the systemic lupus erythematosus drug market. If approved, Benlysta will be the first agent to launch for systemic lupus erythematosus in more than 50 years.
If Benlysta ™ obtains FDA approval, lupus patients will in fact have the first ever dedicated drug for lupus. See my article below based on data from Dr. David Roth, Director of Clinical Development for Immunology for GlaxoSmithKline. First, here is an update from Human Genome Sciences and GlaxoSmithKline, the co-developers of Benlysta.
November 2 09: – Human Genome Sciences and GlaxoSmithKline announce positive results in second of two phase 3 trials of Benlysta in systemic lupus erythematosus. See: http://www.hgsi.com/.
| HUMAN GENOME SCIENCES AND GLAXOSMITHKLINE ANNOUNCE POSITIVE RESULTS IN SECOND OF TWO PHASE 3 TRIALS OF BENLYSTA™ IN SYSTEMIC LUPUS ERYTHEMATOSUS |
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- BENLYSTA (belimumab) 10 mg/kg plus standard of care met its primary efficacy endpoint by achieving a statistically significant improvement in patient response rate versus placebo plus standard of care at Week 52 in BLISS-76 – - Primary efficacy endpoint met in two pivotal Phase 3 trials, as specified by Special Protocol Assessment agreement with FDA – ROCKVILLE, Maryland, and LONDON, UK – November 2, 2009 – Human Genome Sciences, Inc. (Nasdaq: HGSI) and GlaxoSmithKline PLC (GSK) today announced that BENLYSTA™ (belimumab) met the primary endpoint in BLISS-76, the second of two pivotal Phase 3 trials in seropositive patients with systemic lupus erythematosus (SLE). BLISS-76 study results through 52 weeks showed that belimumab 10 mg/kg plus standard of care achieved a statistically significant improvement in patient response rate as measured by the SLE Responder Index at Week 52, compared with placebo plus standard of care. Study results also showed that belimumab was generally well tolerated, as demonstrated by a similar rate of discontinuations due to adverse events across treatment groups, with overall adverse event rates comparable between belimumab and placebo treatment groups. “The BLISS-76 results confirm our view that BENLYSTA has the potential to become the first new approved drug in decades for people living with systemic lupus,” said H. Thomas Watkins, President and Chief Executive Officer, HGS. “We take great pride in the innovation and scientific rigor that has made it possible to bring BENLYSTA to this point. We plan to submit marketing applications in the first half of 2010, following discussions with regulatory authorities in the United States, Europe and other regions. We will continue to work with GSK to advance this drug to the market where it may benefit patients with significant need.” Carlo Russo, M.D., Senior Vice President, Biopharm Development, GSK, said, “The results from this second pivotal Phase 3 trial reinforce our belief that belimumab could deliver a significant therapeutic option for patients with lupus who have had no new treatment in fifty years. We look forward to continuing our collaboration with HGS in order to bring this important medicine to patients.” The data from the BLISS-76 study were analyzed after 52 weeks, in accord with the study protocol, in support of a potential Biologics License Application in the United States and Marketing Authorization Applications in Europe and other regions. However, the BLISS-76 study is ongoing and will continue for 24 more weeks. Additional data will be available following completion of the full 76-week study period. Belimumab is an investigational drug and the first in a new class of drugs called BLyS-specific inhibitors. Belimumab is being developed by HGS and GSK under a co-development and commercialization agreement entered into in August 2006. Key Findings from BLISS-76“We are delighted that the efficacy of treatment with belimumab plus standard of care was superior to placebo plus standard of care in both BLISS-52 and BLISS-76, with overall adverse event rates comparable to placebo plus standard of care,” said David C. Stump, M.D., Executive Vice President, Research and Development, HGS. “Belimumab met the primary endpoint in both pivotal Phase 3 trials, as specified by the Special Protocol Assessment Agreement with FDA. We look forward to the full presentation of the BLISS-76 52-week results at an appropriate scientific meeting, hopefully in the first half of 2010.” Topline BLISS-76 results include:
“The lupus community has waited for decades for one positive Phase 3 trial of an investigative drug developed for lupus. Now we have two. Based on the data we now have in hand, we have cause for hope that belimumab may emerge as a significant new treatment for lupus,” said Joan T. Merrill, M.D., a study investigator, Program Chair, Clinical Pharmacology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, and Professor, Department of Medicine, University of Oklahoma Health Sciences Center. |
copyright Human Genome Sciences 2009
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Lupus Patient Perspective of Benlysta copyright Regan Mizuno, Harmonics Engineering Services, LLC 2009 All Rights Reserved
A new drug for systemic lupus is potentially on the horizon. This is groundbreaking news. The drug is called Benlysta and has been codeveloped and tested by Human Genome Sciences (HGS) and GlaxoSmithKline (GSK). If approved by the FDA, it would be the only drug ever specifically designed for lupus. I realize this does not sound plausible, and here’s the explanation. Curiously, the drugs that we currently use for the treatment of lupus were initially designed to treat other diseases, and the discovery that these drugs could be used to treat lupus was accidentally stumbled upon. Current methods of treatment of systemic lupus include cytotoxic drugs such as Cytoxan (a chemotherapy used for breast cancer) and immune suppressants (prednisone). Should Benlysta earn the ever-important approval from the FDA, Benlysta would also be the first new drug in 50 years to be approved for use in lupus. A successful 52 week trial has given lupus patients hope. Pending another round of successful testing in a 76-week trial (the 52-week trial results will be presented in November, 2009), a new treatment option may be available.
This is terribly exciting. Obviously, lupus patients like me are very interested in this potentially helpful drug. And I personally would like to know Benlysta’s efficacy during the trials as well as its mechanism of action. To learn the answer to some of these questions, I sought the opinion of Dr. David Roth, Director of Clinical Development for Immunology for GSK. I was delighted to learn that Dr. Roth’s specialty is nephrology, as I myself had been treated for kidney disease caused by lupus. My treatment was a regimen of Cytoxan for 2.5 years. Dr. Roth has been working closely on the development of Benlysta and the trials.
Systemic lupus erythematosus (SLE), or lupus, is a chronic and sometimes fatal autoimmune disorder. Lupus is not well known, even though it is more prevalent than AIDS and Multiple Sclerosis combined and affects more than 1.5 million Americans. Lupus affects primarily women of childbearing age, and these women are predominantly women of color. Lupus is a leading cause of premature cardiovascular disease, kidney disease, and stroke among young women, says the Lupus Research Institute.
My first question to Dr. Roth was a hypothesis. I asked: if there exists a universal, basic mode of operation in lupus, in all its forms, might all lupus patients, no matter what their disease manifestations are, potentially benefit from a successful, universal lupus drug?
Dr. Roth began his answer by saying that lupus, in general, is a disease of autoimmunity, where one’s own body produces antibodies against one’s self, called “autoreactive antibodies”, or “auto-antibodies”. Auto-antibodies attack healthy tissue, including the heart, lungs, kidneys, brain, blood, and skin.
He proceeded to explain: in normal human functioning, the body produces B lymphocyte cells. (I did some quick research of my own, and learned that B lymphocytes are white blood cells manufactured in the bone marrow, and they identify antigens). B Lymphocytes then produce antibodies that attack antigens. Antigens are commonly thought of as foreign objects such as viruses or bacteria that enter our body; however, antigens are actually contained on the surface and inside the viruses and bacteria. In general, antigens are substances capable of inducing a specific immune response. Antigens are often indeed foreign proteins (or parts of them) that enter the body via an infection. However, sometimes the body’s own proteins, expressed in an inappropriate manner (and this will be further explained below), are treated like antigens by the immune system. This information was taken from the Dalhousie University Faculty of Medicine “Immunology Bookcase” as published on: http://pim.medicine.dal.ca/atg.htm and is further explained below by Dr. Roth.
Doctor Roth continued: B lymphocytes’ primary function is the production of antibodies. B lymphocytes also react to our own bodies (by producing auto-antibodies). Now, a certain amount of autoreaction is normal. Normally, the B lymphocytes produce a normal amount of auto-antibodies, and then the B lymphocytes die off (and therefore stop producing auto-antibodies).
There is also a protein in our bodies called BLyS, which stands for “B lymphocyte stimulator”. BLyS is necessary for normal functioning of the human body, because BLyS is important to the survival and stimulation of our B Lymphocytes. Basically, the BlyS protein boosts our B lymphocytes in the following two ways: BLyS is one of the proteins that makes it more likely that B Lymphocytes that produce autoantibodies will survive (remember, they’re supposed to die off). Secondly, BLyS makes those autoreactive B lymphocytes that survive more active. A normal amount of BLyS is good. However, when BLyS is present in high amounts, it stimulates an overabundance of B lymphocytes, which in turn causes the production of an overabundance of long-livingauto-antibodies. In other words, in high amounts, BLyS allows autoreactive cells to overcome their natural tendency to die off. That is basic to autoimmune disease and lupus.
The mechanism of action of Benlysta is to block BLyS. Therefore, Dr. Roth hopes that by inhibiting BLyS, all forms of lupus will be improved.
However, he stressed that it is necessary to see such improvement happen within the clinical trials to be able to make that statement definitively.
Therefore, in summary, and in my lay-person terms, in a systemic lupus patient, too much BLyS leads to the production of too many auto-antibodies. And, too much BLyS leads to longer-living auto-antibodies. It’s like fleas – a small amount of fleas may be tolerable, but an abundance of fleas is a not a good thing, and, fleas, especially in large numbers, are not easy to get rid of. Theoretically, by blocking BLyS in systemic lupus patients, the destructive overproduction of auto-antibodies (which attack our organs – and attacked my kidneys) will be stopped, and symptoms will subside.
So, that’s the theoretical bit of it. Let’s move on to the details of the trial.
The 52 week trial, called BLISS-52, showed success. That is, it met its primary endpoint. The primary endpoint was a patient response defined by an improvement in the SELENA SLEDAI score of 4 points or greater, no clinically significant BILAG worsening, and no clinically significant worsening in Physician’s Global Assessment.
The SELENA SLEDAI is a disease activity scale that indicates a clinically important reduction in SLE disease activity. The BILAG measures severity of flares as they affect organs, and the Physician’s Global Assessment defines worsening as an increase of 0.30 points or more from the patient’s baseline.
Being that I was affected severely by lupus, I wanted to know if the drug might be applicable to me, and patients like me, who have suffered organ involvement.
I asked Dr. Roth if he hoped for “severe” SLE prevention. Dr. Roth explained that the patients in the study were moderately ill to severely ill. The study that was completed and being analyzed was not specificallya lupus nephritis trial per se, but the trial did include patients with lupus nephritis. Lupus nephritis patients are also included in the North American and European BLISS-76 trial. The trials were not specific to lupus nephritis patients. However, there is hope that the drug can benefit lupus nephritis patients.
Dr. Roth continued by saying there has always been a big focus on better lupus nephritis treatment. I was glad to hear this, because in my opinion, my treatment of Cytoxan (wherein the goal was to suppress the immune system) was archaic. Barbaric, even. The hope is that Benlysta will prove beneficial to moderately ill patients as well as severely ill patients. Right now HGS does not have the data to be able to make any kind of claim. However, if enough promise was shown in the improvement of certain subsets of patients (those with heart involvement, those with kidney involvement, for example), specific studies of those types of patients will be incited. HGS will therefore analyze the BLISS-52 trial results to see if they can detect patterns within such subsets of patients.
If HGS and GSK do indeed achieve two positive trials in general lupus, specific trials may then be designed. Personally, that is what I hope for. I’d like to see a study done on patients like me, as well as cardiac patients, so I can feel a sense of assurance such that if and when I get attacked again, I can have a mechanism to turn to that is far more favorable to chemotherapy.
Dr. Roth stated that the trial was very consistent.
“Consistent in what way?“ I asked. Dr. Roth described lupus as a variable disease – that even within a single patient, there are relapses and remission periods (tell me about it). From what I have learned and seen, lupus is an individual disease. Everybody’s lupus is different. No two patients are alike. Dr. Roth continued to say that when judging efficacy of trial drugs by looking at one patient and then another patient, it can be difficult to see improvement. However, when looking at different ways that lupus manifests itself (different organs, different patterns of worsening, fatigue, etc.) and different ways of measuring lupus activity, each with its own pros and cons (SELENA SLEDAI, BILAG, flares) and putting all these together into a total picture lets you see whether these different ways of looking at lupus are giving you the same picture. And looking at all these patterns as a whole, it seems that the results of the trial are consistent in the way the patients fared.
It should be noted that meeting this endpoint is significant, as it is a higher hurdle to overcome than, say, an improvement in labs. As we lupus patients know, lupus is a clinical disease. Personally, I can have a “bad” lab result and feel OK. My doctor becomes far more concerned when I have normal labs but feel terrible. So there is something to this physician’s global assessment, that’s for sure.
In addition to measuring each patient’s SELENA SLEDAI, BILAG, and Physician’s Global Assessment, the patients’ labs were also checked. HGS/GSK checked double-stranded DNA, ANA, complements, albumin, protein in the urine, and more.
Heart patients were used in the trial also, if they were stable. (If they had just had cardiovascular (CV) involvement, they were allowed to be in trial if they were stable. If they had had a history of CV, or had current CV involvement that did not make them unstable, they were allowed to be in the trial). And if they’d had an active CV involvement but were on stable treatment, they could be in the study. So, the trial did include “stable but serious” heart patients and nephritis patients. I found this very interesting, and brave al all people involved, especially the patients, to test this drug to the nines. People with end stage kidney disease (where the kidneys are no longer functioning) were not allowed in the study. But if they’d had active nephritis that was on stable treatment, they were allowed in the trial.
The analysis has not yet been done to determine if this particular subset of patients also benefitted from the Benlysta. However, again, should both trials provide improvements in general lupus, a subset analysis on heart and nephritis patients may be conducted.
Bottom line, says Dr. Roth, is that as hopeful as this study is, it is only the first study. We really need to see consistent data in the second study. At that point, we’d be moving forward.
Everybody, stay tuned! And in the meantime, here are some links to both HGS and GSK for more information:
Copyright © 2009, Harmonics Engineering Services, LLC, all rights reserved