BETHESDA, Md. ( TheStreet) -- Human Genome Sciences ( HGSI) can take a big step towards marketing its first blockbuster product next week when a panel of independent experts convenes to review the lupus drug Benlysta. The U.S. Food and Drug Administration advisory panel meets Nov. 16 and will vote whether or not to recommend Benlysta's approval as a treatment for lupus, an autoimmune disease that has gone 50 years without a new, effective therapy for affected patients. The FDA is expected to post online its own review of Benlysta on Friday, Nov. 12, in advance of the FDA panel meeting. That review will be available for FDA web site I will be live-blogging the Benlysta FDA panel on Nov. 16. You can register below for an email reminder. Here's what you need to know about this important upcoming event: Will the FDA panel recommend Benlysta's approval? Yes or No? Wow, you're not wasting any time getting to the meat of the matter. Do you mind if I offer a nuanced answer? Yes, investor sentiment strongly favors a recommendation for approval. The risk is that FDA advisory panels often go off script. That's never been more apparent than in recent months so don't for a second consider Benlysta a sure thing. Lupus has proven intractable to treatment with new drugs for years, yet Human Genome Sciences managed to conduct two, large phase III studies of Benlysta, each with positive results. Lupus patients are desperate for a new drug. How can Benlysta's approval be in doubt? Benlysta's approval is probably not in doubt, but FDA advisory panels aren't coronation ceremonies. The FDA and the experts on the panel are likely to raise questions about just how much patients benefit from Benlysta treatment and for how long; they may quibble over the results from the two studies, the second of which wasn't as successful as the first; and they'll closely examine Benlysta's safety because advisory panels, especially recent iterations, have been obsessed with drug safety. Human Genome Sciences devised a unique way to measure the clinical benefit of Benlysta in lupus patients. Will this work for the company or against it at the FDA panel? The SLE Responder Index (SRI) devised by Human Genome Sciences isn't so much a brand new way of measuring clinical benefit in lupus patients as it is a composite of three existing measures of disease activity. Most importantly, FDA agreed that Human Genome could use the SRI as the primary endpoint in its phase III clinical trials. If FDA told Human Genome that it was okay with the SRI, then no problem, right? Right, except that the experts on the panel aren't the FDA, so it will be interesting to hear how they react to the data. The SRI sets a relatively high bar for response and includes tests of organ involvement (the BILAG score) and overall disease activity (SELENA SLEDAI) that FDA favors in lupus clinical trials. You said that one of the Benlysta clinical trials was more positive than the other. Can you explain? The first phase III study, known as BLISS-52, was conducted outside the U.S. and produced the most positive results. Lupus patients treated with a high dose of Benlysta for one year demonstrated a 14% improvement in the SRI, adjusted for the benefit shown by patients treated with placebo. The result was statistically significant.
A lower dose of Benlysta also demonstrated a statistically significant benefit over placebo. The second phase III study known as BLISS-76 enrolled mostly U.S. patients. The primary endpoint of the study measured response at one year like in BLISS-52, but as the study title implies, Benlysta's effect was also measured out to 76 weeks. BLISS-76's results were mixed. At 52 weeks, the high dose of Benlysta demonstrated a 9.4% improvement in the SRI adjusted for placebo -- lower than the benefit seen in BLISS-52 but still statistically significant. The placebo-adjusted benefit for the low dose of Benlysta was only 6.8% and was not statistically significant. When BLISS-76 was analyzed at 76 weeks, neither Benlysta dose demonstrated a statistically significant improvement over placebo as measured by SRI response. The primary endpoint for BLISS-76 was measured at 52 weeks where the high dose of Benlysta was effective and statistically significant. Isn't that good enough? It should be but expect some debate at the panel. The results of BLISS-76 suggest Benlysta's benefit wanes over time. At the more effective high dose, for instance, Benlysta's SRI-measured improvement fell from 9.4% at 52 weeks to 6.1% at 76 weeks. Benlysta also failed to hit a bunch of the key secondary endpoints, including the percentage of patients with decreased steroid use, in the study. You're quite handy with all these Benlysta data. Thanks, but credit must go to ISI Group biotech analyst Mark Schoenebaum and a very handy Human Genome Sciences slide deck he assembled for his clients to prep them for next week's FDA panel. Can I assume that Human Genome will be prepared to argue in favor of Benlysta's approval? Absolutely. Remember, drugs are approved when the totality of the data demonstrate a clinically meaningful benefit to patients that outweigh the risks. In this case, lupus is a disease that affects patients differently, making it difficult for a single measure of benefit to accurately capture all patients in a single clinical trial.
This is why Human Genome came up with the SRI to assess Benlysta's benefit. The primary endpoint was met in both phase III studies and all the data, when pooled together, further demonstrate the drug's benefit. Human Genome performed an analysis using a more stringent definition of SRI which demonstrated Benlysta's efficacy even out to 76 weeks. While post-hoc, it does bolster the argument in favor of the drug's approval. And don't forget the context of lupus, as well. We're talking about a disease in which no new drug has been approved for 50 years. Until Benlysta came along, lupus was a disease in which good drugs came to die. You haven't mentioned anything about safety. Is Benlysta safe? The two BLISS studies failed to uncover any significant safety concerns associated with use of Benlysta. With that said, the FDA panel may examine what appears to be an increased cancer risk tied to Benlysta, although the numbers are very small. The rate of malignancy in Benlysta patients was 0.53% compared to .018% in placebo patients. Um… That's a three-fold increase in malignancies! How is that not a big deal? Only one cancer death in the Benlysta trials was reported and that patient died after just 21 days of treatment. The long-term follow-up from phase II studies of Benlysta doesn't indicate a cancer risk increase after 5 years; and other drugs used to treated autoimmune diseases carry cancer risk warnings in their labels but are still widely used. Any other safety risks or potential worries? Benlysta may be responsible for an increased risk of infections, according to pooled data from the BLISS studies, but again, infection risk is a well-known side effect of drugs used to treat autoimmune diseases. African-Americans didn't respond as well to Benlysta, which could be brought up by the panel since lupus is 2-3 times more common in African-Americans. You mentioned before that Benlysta is a potential blockbuster drug. Just how big could it be and what impact will it have on Human Genome's stock price? Analyst estimates for Benlysta's commercial potential vary but generally speaking range from $2 billion to $4 billion, depending on pricing assumptions and market share gains in U.S. and Europe, where the drug will be marketed by partner GlaxoSmithKline ( GSK). One recent area of post-approval concern for investors has been the trajectory of Benlysta's commercial launch, especially given what is likely to be a tough reimbursement environment. Human Genome has been asking analysts who cover the stock to temper Benlysta sales estimates in 2011 because insurers may be slow to cover the drug, or place obstacles in the way of patients who want to use Benlysta before trying other older and less costly lupus therapies first.
ISI's Schoenebaum has a $32 price target on Human Genome, which assumes a positive FDA advisory panel, FDA approval and sales of about $2.5 billion in 2015. Sanford Bernstein analyst Geoff Porges likewise carries a $32 price target on Human Genome after downgrading the stock to market perform in September: "HGSI's stock has been one of the strongest performers in the biotech group over the summer and has been boosted by confirmation of BenLysta's priority review status on August 19, as well as speculation about M&A potential for the company. We now see the company as more or less fully valued in the $30 range, with less upside than other names in the mid cap group at current prices. Our launch revenue and earnings expectations are tempered by what is likely to be a tough reimbursement environment in the US. Therisks associated with near term regulatory events now seem more or less equivalent to the upside from a take-out bid, which seems unlikely to emerge before year end," Porges wrote. --Written by Adam Feuerstein in Boston. >To contact the writer of this article, click here: Adam Feuerstein. >To follow the writer on Twitter, go to http://twitter.com/adamfeuerstein. >To submit a news tip, send an email to: firstname.lastname@example.org.