March 17 (Bloomberg) -- Bayer AG, the German drugmaker developing a new anti-clotting pill with Johnson & Johnson, had its biggest drop in six years in Frankfurt trading after U.S. regulators said the medicine may cause bleeding or liver damage.
Bayer, of Leverkusen, Germany, fell 3.77 euros, or 10 percent, to 32.69 euros, its largest percentage decline since Feb. 25, 2003. J&J, of New Brunswick, New Jersey, dropped a penny to $50.72 at 4 p.m. in New York Stock Exchange composite trading.
The drug, Xarelto, may cause bleeding in “significantly more patients” than Sanofi-Aventis SA’s Lovenox, the standard treatment, and increase the risk of liver damage, staff at the Food and Drug Administration said in a review released today. The report “was a scare” to investors counting on Xarelto to boost Bayer’s earnings, said Karl-Heinz Scheunemann, an analyst at Landesbank Baden-Wuerttemberg in Stuttgart, Germany.
“A drop of 10 percent is a bit exaggerated, especially since the full potential of the drug won’t be reached until the middle of the next decade,” Scheunemann said today in a phone interview. “I don’t know if this isn’t being over-interpreted, if people aren’t being too careful.”
The FDA’s Cardiovascular and Renal Drugs Advisory Committee will discuss the agency’s report when the panel meets on March 19 to recommend whether Xarelto, known chemically as rivaroxaban, should be cleared for U.S. sales. The drug is approved in Europe and Canada.
U.S. Market
Xarelto would be the U.S.’s first new oral anticoagulant since warfarin was approved in 1954. The FDA is considering Xarelto for patients undergoing surgery to replace hips and knees. U.S. sales may reach $1.6 billion in 2013 if the drug is approved for additional uses, including stroke prevention in patients with irregular heart rhythms, said Larry Biegelsen, an analyst at Wachovia Capital Markets in New York, in a note today. Sanofi’s Lovenox must be injected.
J&J’s Ortho-McNeil unit has rights to sell the drug in the U.S. and would pay royalties of as much as 30 percent to Bayer if Xarelto is approved, according to Christian Hartel, a Bayer spokesman.
Liver risks helped spell the demise of the last experimental oral anticoagulant, AstraZeneca Plc’s Exanta. The U.S. rejected the drug in 2004. Although approved in Europe, it was later pulled from the market because of liver toxicity.
Lacking Safety Data
The FDA reviewers raised concerns about the lack of long- term safety data for Xarelto and the likelihood that doctors would prescribe it for unapproved, or “off-label,” uses. Data from long-term studies now being conducted by the companies “will be needed to fully evaluate” the liver risks, wrote Min Lu, who conducted the FDA’s clinical review.
“Previous experience with Exanta that causes drug-induced liver injury suggested even short term tolerance does not necessarily predict long term safety,” Lu wrote. “Because rivaroxaban is an oral anticoagulant that doesn’t require routine monitoring during treatment, off-label, long-term use could be widespread in clinical practice.”
Clots occur naturally to prevent prolonged bleeding when a blood vessel is damaged. Those in the deep veins of the lower leg or thigh can be deadly if they break off and block blood flow to the lungs, a condition called pulmonary embolism.
Doctors usually prescribe anticoagulants to patients undergoing hip- or knee-replacement surgery to prevent deep vein clots. They are different from antiplatelet drugs such as Plavix, made by Sanofi and Bristol-Myers Squibb Co., which prevent clots from developing in the arteries and causing heart attacks.
Less Clotting Than Lovenox
Warfarin is sold by New York-based Bristol-Myers Squibb Co. as Coumadin and by several generic-drug companies. Doctors are eager for a safer alternative because the product, first developed as a rat poison, is the second-most-common drug, after insulin, that’s implicated in emergency-room visits for reactions, according to the FDA.
Once-a-day Xarelto showed a more than 50 percent reduction in clotting or deaths when compared with twice-a-day Lovenox across four studies of more than 12,500 patients, according to J&J. Major bleeding, a side effect of anti-clotting drugs, occurred in 0.39 percent of Xarelto patients and 0.21 percent of Lovenox patients. The increase wasn’t statistically significant in J&J’s analysis.
Deaths and Complications
One patient on Xarelto died of gastric bleeding six days into treatment. There were more deaths from cardiovascular complications and pulmonary embolism in the Lovenox group, although that group had no deaths from major bleeding. Hip patients were treated for five weeks and knee patients for two.
The FDA has requested a low-dose Xarelto tablet for patients with impaired liver or kidney functioning or those on other medications that may increase the risk of side effects. J&J said today that it is working on that with the FDA.
Lovenox was approved in 1993 and is Sanofi’s biggest product with U.S. sales of 1.63 billion euros ($2.39 billion) last year. Not all of that market would be vulnerable to competition with Xarelto at first, since Lovenox is also approved for patients at risk for venous clots because of abdominal surgery or an acute illness that severely restricts mobility.
Sanofi fell 4 cents to 41.76 euros today in its hometown of Paris.
Paul Chew, Sanofi’s head of U.S. research and development, said injections are better than pills for some hospital patients, including those recovering from abdominal surgery.
“If you really want to make sure patients get their medication in a hospital, the injection is ideal,” Chew said in a March 13 phone interview. “That’s one way of assuring the dose is totally administered.”
The FDA is scheduled to decide on Xarelto by May 28. The agency usually follows the recommendations of its advisory panels, though it isn’t required to do so. Bayer, which has marketing rights outside the U.S., won Canadian approval in September and European approval in October.
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