Pharma: July 2009 Archives

Trachoma, the leading infectious* cause of blindness in the developing world, has been eliminated from Ghana, Mexico, and Saudi Arabia, according to a press release from the Carter Center and the International Trachoma Initiative. Ghana is the first sub-Saharan African country to purge the disease.

Elimination of trachoma** was achieved by using the so-called SAFE strategy of the World Health Organization—which includes eyelid surgery, antibiotics (ie, azithromycin), facial cleanliness, and environmental improvements. The strategy was used successfully 3 years ago to wipe out trachoma in Iran, Morocco, and Oman and is the basis of the WHO's Alliance for the Global Elimination of Blinding Trachoma by the year 2020.

Azithromycin (Zithromax) is currently being donated by Pfizer, in conjunction with the Edna McConnell Clark Foundation. The drug company and the foundation originated the International Trachoma Initiative in 1998.

* Caused by the bacteria Chlamydia trachomatis.

** Defined by WHO as 1) elimination of blinding cases of trachomatous trichiasis through surgery (or at least offering surgery to all cases); 2) reducing cases of trachomatous follicular conjunctivitis in adults to fewer than 1 per 1000; and 3) reducing the prevalence of trachomatous follicular conjunctivitis in children (age range, 1-9 years) to less than 5%.

Image of trachomatous conjunctival scarring from WHO trachoma grading cards.

Pharma biz sources

are buzzing with the PR news that belimumab (Benlysta*; GSK, Human Genome Sciences) improved the disease activity of systemic lupus erythematosus (SLE) in a 1-year, 2-dose, placebo-controlled, phase 3 study (BLISS-52). The mAb also enabled the reduction of the corticosteroid dosage.

The primary endpoint of the study, which was met with belimumab treatment, was a combination of 4 recognized measurements of SLE activity.** The reported patient response rates were 57.6% for belimumab 10 mg/kg; 51.7% for belimumab 1 mg/kg, and 43.6% for placebo (respective P values = .0006 and .011, vs placebo). All patients received "standard of care." Individual secondary measures were also consistent with the statistically significant primary-endpoint results.

The rates of serious infections were 6.1% and 5.9% with belimumab and placebo, respectively, and rates of common adverse advents—headache, arthralgia, URI, UTI, and influenza—were also comparable between the 2 treatments. An important footnote in this relatively short-term study: no observed malignancies.

Results of a longer-term, placebo-controlled, phase 3 study with belimumab in SLE, BLISS-76, are expected in November (although the combined primary endpoint will be assessed at 52 weeks). As in BLISS-52, 2 belimumab dosages, 1 and 10 mg/kg, have been randomly assigned. Positive results will undoubtedly bolster a biologics license application to the FDA.

Belimumab is a human mAb that inhibits the activity of B-lymphocyte stimulator (BLyS), which promotes the survival of (auto)antibody-producing B cells. The drug was discovered by Human Genome Sciences, which entered into a codevelopment and comarketing agreement with GSK 3 years ago. Other anti-B-cell therapies in clinical development for SLE include rituximab (Rituxan; Genentech), epratuzumab (Immunomedics), and ocrelizumab (Genentech, Biogen) aka Son of Rituxan.

The most recent great hope for SLE, mycophenolate mofetil (CellCept; Roche) died a death of noninferiority, after it performed no better than cyclophosphamide for the induction treatment of lupus nephritis.

According to the Lupus Foundation of America, roughly 1.5 million Americans and more than 5 million people in the world have lupus.

mAb = monoclonal antibody; URI = upper respiratory tract infection; UTI = urinary tract infection.

* Formerly LymphStat-B.

** A reduction from baseline in the SELENA SLEDAI score of at least 4 points; no worsening in Physician Global Assessment (PGA); no new BILAG-A organ domain score; and no more than one new BILAG-B organ domain score from baseline.

Although the Accreditation Council for Continuing Medical Education (ACCME) reports that total income for all CME providers dropped only 7% from 2007 to 2008, total income for publishing and education companies (ie, MECCs) dropped 20%. These data are derived from the ACCME's 2008 Annual Report, which was released last week. The income drop for MECCs is largely due to loss of commercial (ie, pharma) support, which fell 22% from 2007 to 2008. Also 6 fewer MECCs reported income data to the ACCME in 2008 (from 150 in 2007).

CME Income and Expense Data for Publishing/Education Companies, 2004-2008

Net income (total income – total expense) for all reporting MECCs in 2008 was $157,608,100, compared with $215,106,000 in 2007 (percentage drop, 27%). In addition, the percentage of total CME income for MECCs (among all providers) dropped below 30% (to 28%) for the first time in at least 5 years. General sentiment in the CME-MECC biz is that last year's income drop is the beginning of a downward trend, not a one-time aberration.

MECCs = medical education communications companies.

And another thing that Avastin (bevacizumab; Genentech) may be good for:

The anti-VEGF monoclonal antibody improved hearing loss and reduced tumor volume in patients with growing vestibular schwannomas. The conclusions are based on data from a small, first-of-its-kind study of patients with neurofibromatosis (NF) type 2—data which are available in an early release article from The NEJM.

Ten consecutive patients with NF type 2 and progressive vestibular schwannomas (who were not candidates for or declined the standard treatment of surgery and radiation therapy*) received at least one dose of bevacizumab (5 mg/kg every 2 weeks). The median annual growth rate of schwannomas before treatment was 62%, and the median duration of treatment was 12 months. (The rationale for assessing bevacizumab in NF-associated schwannomas is based on the expression of VEGF in tumor cells. However, the expression of the VEGF receptor, VEGFR-2, on tumor vessels is not particularly high—which suggests that an anti-VEGF-receptor drug is less likely to be of benefit than bevacizumab.)

In a retrospective analysis, 9/10 tumors shrank (best median response, 26% reduction) after bevacizumab treatment, and 6 demonstrated an imaging response. Only 1 patient experienced an increase in tumor volume (of 32%). Tumor reduction strongly correlated with baseline vasogenic edema on MR images (ie, the mean apparent diffusion coefficent). Improvements in hearing (at <12 weeks) were observed in 5 of 7 eligible patients and were progressive and durable (up to 16 months) in most.

This pilot study was not funded by Genentech; although 1 author (Gregory Sorensen, MD) reported receiving grant support from the company.

NF2 is a dominantly inherited disorder with a prevalence of 1 in 25,000. The most common tumor type associated with the condition is vestibular (or acoustic) schwannomas, benign tumors of the 8th cranial nerve. Growth of tumors causes progressive hearing loss, as does surgical and radiation therapy. Progressive vestibular schwannomas can also produce brainstem compression.

In May, the FDA approved Avastin for the treatment of the uniformly fatal brain tumor, glioblastoma multiforme, after standard therapy.

VEGF = vascular endothelial-cell growth factor.

* Eight patients were at high risk for complete hearing loss with standard therapy.