Lilly Tries To Boost Evista Profile Via Comparative Trial With Fosamax

Lilly will compare the osteoporosis agent Evista (raloxifene) to Merck's Fosamax (alendronate) in a head-to-head trial designed to better position the selective estrogen receptor modulator against its most successful bisphosphonate competitor.

"There is a great need for clarity" for doctors and patients in deciding between various osteoporosis therapies, Lilly U.S. Women's Health Leader Deirdre Connelly told a July 25 conference call. "The osteoporosis market is growing increasingly crowded, and we are determined to...continue to differentiate [Evista] from competitors."

"We believe Evista is second-to-none in terms of bone protection, and we are willing to take on the leading bisphosphonate to show it," Connelly declared. The trial is slated to begin in October.

Lilly may partially be responding to American Medical Association guidelines on managing osteoporosis, which advise doctors: "because most patients with osteoporosis are at increased risk for both vertebral and non-vertebral fractures, one may want to consider an agent that has been shown to reduce both."

"Estrogen (on the strength of epidemiologic studies) and bisphosphonates (on the strength of prospective trials) may be an appropriate choice based on their demonstrated ability to reduce the risk for all fractures," the guidelines continue.

On the other hand, "raloxifene and calcitonin have not, as yet, been shown to reduce non-vertebral fractures, and therefore, might not be useful in patients who are not candidates for estrogen or bisphosphonates."

Evista received a supplemental indication for risk reduction in first vertebral fracture, but not for non-vertebral fracture. Fosamax is indicated for risk reduction in both types of fractures.

The Evista/alendronate (EVA) trial will randomize 3,000 postmenopausal women with osteoporosis to either Evista 60 mg/day or Fosamax 10 mg/day. Early results are expected in 2006. Lilly explained that once-weekly Fosamax is not being used since it has not directly demonstrated fracture reduction in clinical trials.

EVA's primary endpoint will be the number of women experiencing at least one new osteoporosis fracture of any type, "including those of the spine, hip and wrist," Lilly said. Secondary endpoints will examine "incidence of osteoporotic fractures at specific sites," as well as "incidence of newly diagnosed breast cancer and other safety-related endpoints."

The AMA guidelines add that bisphosphonates, and especially raloxifene, may be preferable in women who are at high risk for breast cancer, while estrogen and raloxifene are "attractive options" for those at risk for heart disease. The American Heart Association recently withdrew its suggestion that patients take estrogen for cardioprotection alone (¹ (Also see "Wyeth Premarin Biannual Price Increases To Boost "Cheap" 60[cents] Daily Cost" - Pink Sheet, 30 Jul, 2001.)).

Lilly's multiple outcomes of raloxifene evaluation (MORE) study suggested a reduced incidence of estrogen receptor-positive breast cancer, but was not sufficient to garner an indication.

Lilly has two ongoing trials aimed at the breast cancer indication: the study of tamoxifen and raloxifene (STAR) trial comparing the reduction in incidence of breast cancer among high-risk women; and the RUTH trial, which is designed to evaluate whether raloxifene reduces risk of heart attack and cardiac death in postmenopausal women at risk for coronary heart disease; the trial has enrolled 10,101 patients and could produce results in 2005.

Lilly's continuing outcomes relevant to Evista (CORE) study - which follows a subpopulation from the MORE trial - has also been determined inadequate by FDA for a breast cancer reduction indication. Early results from CORE are expected in 2004.

Evista global sales grew 25% to $167 mil. in the second quarter compared to the same quarter last year. Connelly said the drug is Lilly's "fastest growing product." Evista still has a long way to go before catching up to Fosamax, however, which grossed $490 mil. in the second quarter. Part of Fosamax' continued success is driven by its once-weekly formulation.

Lilly is trying to expand its osteoporosis portfolio with the addition of Forteo (teriparatide). The recombinant parathyroid hormone was reviewed by an FDA advisory committee on July 27 (² (Also see "Lilly Forteo Osteoporosis Indication Approval Recommended With Restrictions" - Pink Sheet, 30 Jul, 2001.)).