Xolair for Chronic Itch: Magic Bullet or Marketing Hype?

By Jonathan J. Darrow

Earlier this week, the New York Times reported that Xolair (omalizumab), a monoclonal antibody approved in 2003 to treat allergic asthma, had recently shown efficacy in relieving hives patients of chronic itch (See Laurie Tarkan, Drug to Treat Asthma Could Relieve Hives Patients of a Chronic Itch, Study Says, N.Y. Times, Feb. 25, 2013, at A5).  The article noted that a Phase 3 trial (usually, the final phase before FDA approval) showed that a monthly injection of Xolair “significantly reduced hives and itchiness.” Quoting the lead author of the study, the article reported that Xolair “is the magic bullet patients have been waiting for for the last 40 years.”  Is it?

An initial concern is the large number of conflicts of interest associated with the study. An examination of the Phase 3 trial as published in the New England Journal of Medicine (NEJM), on which the New York Times article is based, reveals that the trial was “[f]unded by Genentech and Novartis,” both of which sell Xolair.  The lead author and at least one other co-author of the study have received consulting fees from one or both companies, while another of the co-authors (Karin Rosen) is the medical director for Genentech.  Conflicts of interest, however, do not necessarily mean that the drug is in fact ineffective.  To determine efficacy, one must look at the evidence.

The NEJM study reports that test subjects received either placebo or Xolair at doses of either 75 mg, 150 mg, or 300 mg.  Starting from a baseline itch-severity score of about 14, the data were as follows:

TABLE 1.

<—–Baseline—–>

<—————————After 12 Weeks—————————–>

 

PLACEBO

75 MG

150 MG

300 MG

14

8.9 (+/- 5.6)

8.1 (+/- 6.5)

5.9 (+/- 6.4)

4.2 (+/-6.0)

not statistically significant

significant at p=.001

significant at p=.001

NOTES:

  • Itch-severity scale ranges from 0 (least severe itch) to 21 (most severe itch)
  • Scores other than baseline given as: mean (+/- standard deviation)

These results demonstrate not only statistically significant improvement for the two higher doses of Xolair, but improvement that would seem to be meaningful from the patient perspective (a score of 4.2, for example, seems much lower than the baseline of 14).

However, a number of caveats are in order, as always. First, it is important to note that substantial improvement was seen in the placebo group, with scores diminishing from a baseline of 14 to 8.9, without any study intervention at all (patients in all groups were allowed to continue to “receive stable doses of their pre-randomization H1-antihistamine,” a category that includes Benedryl (dyphenhydramine) or Allegra (fexofenadine), throughout the study period, making true “no treatment” comparison figures unavailable).   Of course, all else equal, patients prefer greater relief rather than less, and Xolair does appear to provide greater relief.  Even at the 300 mg level, however, the mean itch-severity score did not drop below 4.2, indicating that the relief was less than complete.

While the drug seems to be fairly effective, praising it as the “magic bullet patients have been waiting for for the last 40 years” may therefore significantly overstate the case.  Using more restrained language, however, might make it difficult to convince patients (or their insurers) to pay the $500 to $2000 per month needed to buy the drug. That price, however, is for the indication already approved by the FDA. Once Genentech obtains approval for the new indication of itching, the cost may increase even higher.  And the drug company may even sell Xolair (omalizumab) under a new brand name to discourage off label sales, a well-established marketing tactic.

The greatest reason to restrain enthusiasm (and guard your pocketbook), however, is neither Xolair’s absolute efficacy nor its price. It is that many other treatments are already used to treat the itch of hives, including H1 and H2 antihistimines, cyclosporine, hydroxychloroquine, dapsone, methotrexate, sulfasalazine, and intraveneous immunoglobulin. The phase  3 study itself reports these alternatives (see page 2). As the study cautions, none of these have been approved by the FDA for the treatment of hives.  But neither, so far, has Xolair.  Doctor’s instead must currently prescribe them off label, i.e., prescribe them for an indication that is not yet approved by the FDA.  What patients really want to know, however, is not only how effective the drug is, but how much better it is than these alternatives.  Table 1 above should have as many more rows as there are current treatments, to allow for evidence-based comparison. This is what patients want. This is what a sensible healthcare system would provide.  Unfortunately, that data is not presented in the NEJM study.

Is Xolair, then, a breakthrough in this case?  Once again, it is impossible to tell from the study results.  Xolair may be a breakthrough compared to current off-label treatments, it may be equally effective, or it may be less effective.  Eventually, additional studies may help to answer this question.  Until then, however, doctors who prescribe Xolair may be needlessly transferring large sums of money from the public (either directly or via insurance) into the coffers of Big Pharma, while patients may not be receiving the most effective treatment.  For now, then, it is possible that Xolair is just an ordinary metal slug, polished to look its best, rather than the “magic bullet” it is said to be.

(The current label for Xolair can be found here).

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About jdarrow

Dr. Jonathan J. Darrow is a research fellow at Harvard Medical School and a post-doctoral fellow in the Program on Regulation, Therapeutics and Law at Brigham & Women’s Hospital. He holds a BS in biological sciences from Cornell, a JD from University, an MBA from Boston College, and an SJD (a dissertation-based doctorate and the law discipline’s highest degree) from Harvard, where he also completed the LLM program in 2009. After admission to the bar, Dr. Darrow practiced law in the Silicon Valley offices of Cooley Godward and later worked on patent litigation matters at Wiley Rein & Fielding in Washington, DC. He is admitted to practice before the USPTO and has served on the business law faculties of Boston College, Plymouth State University, and Bentley University (current). His legal scholarship on technology, intellectual property, and health has appeared in numerous publications including the New England Journal of Medicine, the Journal of Law, Medicine & Ethics, the Stanford Technology Law Review, the NYU Journal of Legislation & Public Policy, the Northwestern Journal of Technology & Intellectual Property, and the Harvard Journal of Law & Technology, among many others. He is a co-author of two major law textbooks: Cyberlaw: Text and Cases and The Legal and Ethical Environment of Business. Dr. Darrow previously explored the impact of intellectual property on global health during stints at both the World Trade Organization and World Health Organization in Geneva, Switzerland.