February 10, 2005

EXANTA SHOWS SIMILAR EFFICACY TO LOVENOX, WARFARIN, BUT COULD HAVE HEPATOTOXICITY RISK, STUDIES INDICATE

AstraZeneca Plc's pharmaceutical name Exanta (ximelagatran) appears to be as effective as comparator drugs for preventing thromboembolism and treating deep vein thrombosis, but also results in increased liver enzyme levels, according to results of two newly published studies.

The double-blind Thrombin Inhibitor in Venous Thromboembolism Treatment Study enrolled patients with acute deep vein thrombosis with or without pulmonary embolism. A total of 2,489 patients were randomized to six-month treatment with either sanofi-aventis Group's Lovenox (enoxaparin sodium) in combination with adjusted-dose warfarin or Exanta alone to achieve an international normalized ratio of 2.0 to 3.0.

In the intent-to-treat analysis, venous thromboembolism recurred in 26 of 1,240 Exanta-treated patients and 24 of 1,249 Lovenox/warfarin-treated patients. The absolute difference in recurrent venous thromboembolism between the treatment groups was 0.2 percent, which met the prespecified criterion for noninferiority.

The rates of major bleeding and all-cause mortality were also similar between the Exanta and Lovenox/warfarin arms.

However, nearly 10 percent of the patients who received Exanta showed alanine aminotransferase (liver enzyme) levels that had increased to more than three times the upper limit of normal, as compared with only 2 percent of the patients in the combination therapy arm. A retrospective analysis of locally reported adverse events also showed a higher rate of serious coronary events with Exanta than with Lovenox/warfarin.

For the other double-blind study, 3,922 patients with nonvalvular atrial fibrillation and additional stroke risk factors were randomized to adjusted-dose warfarin or 36 mg of Exanta twice daily. The primary objective was to establish noninferiority for preventing primary events (all strokes and systemic embolic events) in an intent-to-treat model.

Primary events occurred in 88 patients; the per-year incidence rate was 1.6 percent for the Exanta group and 1.2 percent for the warfarin arm. The rates of major bleeding were similar between the treatment arms, but total bleeding was lower with Exanta (37 percent per year vs. 47 percent per year).

However, in 6 percent of Exanta-treated patients, serum alanine aminotransferase levels rose to more than three times the upper limit of normal within six months, but typically declined thereafter.

"Further investigation is needed to clarify the risk of serious hepatic reactions and identify predictive features to select appropriate patients for treatment with the pharma brand [Exanta]," one of the research groups concluded.

Both studies can be found in the Feb. 9 issue of JAMA.

In October, the Food and Drug Administration chose not to approve Exanta for the prevention of blood clots, stroke and other clot-induced complications in certain patient groups. An advisory committee had expressed concerns in September about the potential risk of heart attacks and long-term risk of liver damage associated with the pharmaceutical brand drug, The Wall Street Journal had reported.

Friday, January 28, 2005

ASTRAZENECA REPORTS INCREASE IN QUARTERLY, ANNUAL NET INCOME DESPITE NEW DRUG SETBACKS

AstraZeneca Plc reported a 52 percent jump in fourth-quarter earnings, as continued demand for established therapies helped the company offset its failure to gain U.S. approval for two new drugs, as well as the impact of safety concerns over its cholesterol-lowering drug, Crestor (rosuvastatin calcium).

Net profit in the fourth quarter totaled $968 million, $0.59 per share, versus $635 million, or $0.38 per share, in the same quarter last year, the Associated Press reported. Total sales were $5.8 billion compared with $4.9 billion in the fourth quarter of 2003.

Under U.S. generally accepted accounting principles, AstraZeneca's 2004 full-year net income totaled $3.1 billion, or $1.82 per share, compared with net income of $2.3 billion, or $1.33 per share, for 2003.

Worldwide 2004 sales increased to $21.4 billion from $18.8 billion in 2003, outperforming a Reuters poll average forecast of $21.3 billion.

AstraZeneca said it took an $85 million fourth-quarter charge related to Iressa (gefitinib) after a study "did not demonstrate a statistically significant improvement in overall survival for Iressa treatment in patients with advanced lung cancer."

Also, the failure to gain approval from the Food and Drug Administration for anti-clot drug Exanta (ximelagatran) resulted in an additional $71 million fourth-quarter charge.

Sales of Crestor suffered after a senior FDA official raised concerns about the drug's safety last November. But, according to AstraZeneca's chief executive officer, Tom McKillop, "[N]othing has changed in the profile (of Crestor) to say that we shouldn't get a very substantial share of the market." Worldwide sales of Crestor were $908 million in 2004, beating a Reuters-reported analyst forecast of $887 million.

Annual worldwide sales of AstraZeneca's proton pump inhibitor, Nexium (esomeprazole magnesium), were up 15 percent to $3.9 billion, while sales of its atypical antipsychotic drug, Seroquel (quetiapine fumarate), rose 33 percent, exceeding $2 billion.

Shares of AstraZeneca closed at $37.25, up $1.27, or 3.5 percent, in heavy trading on the New York Stock Exchange.

Tuesday, December 21, 2004

ASTRAZENECA PLANS PROCEDURAL CHANGES

AstraZeneca Plc said in a conference call Friday that it will change how it develops its drugs and communicates with regulatory authorities.

The conference call with analysts and investors came after the company released disappointing results from the Iressa (gefitinib) trial. The company had counted on the lung-cancer treatment to help drive sales over the next few years, according to The Wall Street Journal.

To expedite changes within the company, Chief Executive Officer Sir Tom McKillop named Dr. John Patterson as the new executive director to oversee drug development. Patterson most recently held the position of Territorial Business Director. He was responsible for directing the business operations of all the businesses of Zeneca Pharmaceuticals in 130 countries outside the United States.

McKillop said he is also asking Patterson to restructure the company's clinical process as well as "to improve significantly our interfaces with the regulatory authorities." The company is committed to communicating the progress it makes along the way, McKillop said.

Despite the company's recent setbacks, including the Food and Drug Administration rejection of direct thrombin inhibitor Exanta (ximelagatran) and the disappointing sales of cholesterol-lowering therapy Crestor (rosuvastatin calcium), McKillop said 2004 financial performance remains high. He expects earnings per share of at least $2.10 for the year, before exceptional items, any provisions for Iressa assets or additional charges relating to Exanta if it is not approved in France.

October 22, 2004

ASTRAZENECA, NOVARTIS REPORT STRONG PERFORMANCE IN THIRD QUARTER

AstraZeneca Plc and Novartis AG achieved strong financial results in the third quarter of 2004.

AstraZeneca's third-quarter sales increased 7 percent to $5.27 billion, up from $4.80 billion generated in the comparable period last year. Sales of the antipsychotic Seroquel (quetiapine fumarate) jumped 51 percent to $529 million, while sales of the dyslipidemia treatment Crestor (rosuvastatin) reached $260 million. Sales of the ulcer therapy Nexium (esomeprazole magnesium) slid 6 percent in the quarter to $951 million.

The firm's third-quarter operating profit totaled $1.26 billion, up 16 percent from $1.10 billion in the prior year period. Earnings per share, including a $0.17 benefit from exceptional items, reached $0.72, a 56 percent increase from $0.47 last year.

"Despite the recent disappointment with Exanta, the business is performing well. . . . A continuing strong performance in the fourth quarter should yield full year pre-exceptional earnings of around $2.10 per share and will provide an effective platform for growth in 2005," said Sir Tom McKillop, AstraZeneca's chief executive.

In September, the Food and Drug Administration recommended against approval of Exanta (ximelagatran) for three indications: preventing blood clots in veins among patients undergoing knee replacement surgery; prophylaxis of stroke and other clot-induced complications associated with atrial fibrillation; and long-term prevention of blood clots in veins after a patient has received a standard blood clot treatment.

Separately, Novartis' third-quarter earnings increased 21 percent to $1.55 billion, or $0.63 per share, on strong sales of its Diovan (valsartan) hypertension therapy and cancer treatments Gleevec (imatinib mesylate) and Zometa (zoledronic acid). The therapies generated sales of $788 million (28 percent gain), $411 million (47 percent gain) and $262 million (9 percent gain), respectively.

Overall, Novartis' total sales reached $7.06 billion, up 14 percent from $6.21 billion generated in the third quarter of 2003.

The company noted that lower sales growth from its generic division, Sandoz, was offset by a 10 percent increase in consumer health sales, due primarily to double-digit growth in over-the-counter and medical nutrition sales.

Shares of AstraZeneca closed at $40.50, up 40.87, or 2.2 percent, while Novartis shares closed at $47.23, up $0.53, or 1.1 percent, both in moderate trading on the New York Stock Exchange.

October 11, 2004

FDA REJECTS EXANTA

The Food and Drug Administration rejected AstraZeneca Plc's oral anticoagulant Exanta (ximelagatran) Friday, following the advice of an advisory panel that met last month.

AstraZeneca was seeking approval of Exanta to be used for stroke prevention in patients with atrial fibrillation, for prevention of blood clots in patients undergoing knee-replacement surgery and for the long-term secondary prevention of blood clots following standard treatment of a clot.

The firm did not reveal details of the FDA action letter, but the advisory committee expressed concerns in September about the long-term risk of liver damage associated with Exanta. Additionally, panel members had worries about the risk of heart attack in knee-surgery patients who use the drug on a short-term basis, The Wall Street Journal reported.

AstraZeneca said in a press release that it continues to believe in the benefit/risk profile of Exanta and is considering how to proceed further with the FDA.

Exanta is approved in Europe for the prevention of blood clots in patients undergoing hip- and knee-replacement surgeries.

October 7, 2004

ASTRAZENECA AFFIRMS 2004 EPS GUIDANCE, BUT PUSHES FILING DATE FOR GALIDA FORWARD

AstraZeneca Plc said for the full-year 2004, earnings per share would be in the middle of the previously projected $2.00 to $2.15 range, even as it extended its regulatory filing date for Galida, a potential type 2 diabetes treatment. Analysts surveyed by Thomson First Call expect earnings of $2.08 per share, according to CBS MarketWatch.

AstraZeneca said dyslipidemia drug Crestor (rosuvastatin), gastrointestinal drug Nexium (esomeprazole), antipsychotic Seroquel (quetiapine), asthma inhaler Symbicort (budesonide/formoterol) and cancer drug Iressa (gefitinib) will drive sales and earnings growth in the near term, Reuters reported.

However, the company pushed the filing date for Galida from 2006 to 2007 after agreeing to extend long-term follow-up clinical studies to two years. This follows a global regulatory review of the safety and toxicology of the drug class to which Galida belongs-- peroxisome proliferation activated receptor agonists.

AstraZeneca reported in the press release that the Phase III programs for both Galida and Cerovive are progressing well. Cerovive, also known as NXY-059, is being evaluated to determine its effect on disability and neurological recovery in patients who have experienced acute ischemic stroke.

This news comes after a Food and Drug Administration advisory committee recommended last month that the FDA not approve the company's Exanta (ximelagatran). The drug is intended to prevent blood clots, stroke and other clot-induced complications among certain patients. The panel said Exanta's benefits do not outweigh the long-term risk of liver damage and the potential short-term risk of heart attacks in some patients, The Wall Street Journal reported. AstraZeneca said in the press release that it is in discussions with the agency, and the 10-month deadline is Oct. 23.

"With $10 billion in annual sales of newer products growing strongly, good progress across the development portfolio and success in emerging markets, AstraZeneca is well-positioned to overcome the recent disappointment of Exanta and to meet the wider challenges facing the industry," said Sir Tom McKillop, chief executive officer.

The firm added that another 28 New Molecular Entity projects are in Phase I and II development, representing 60 percent more than those in Phase II studies one year ago.

Shares of AstraZeneca closed at $39.64, down 2.3 percent, or $0.94, in heavy trading on the New York Stock Exchange.

September 13, 2004

FDA PANEL RECOMMENDS AGAINST APPROVAL OF ASTRAZENECA'S EXANTA

A Food and Drug Administration panel advised against approval of AstraZeneca Plc's Exanta (ximelagatran) late Friday.

The company was seeking approval for three indications, all of which the panel voted against: preventing blood clots in veins among patients undergoing knee replacement surgery; prophylaxis of stroke and other clot-induced complications associated with atrial fibrillation; and long-term prevention of blood clots in veins after a patient has received a standard blood clot treatment.

The panel said Exanta's benefits do not outweigh the risk of liver damage in some patients in the long-term, The Wall Street Journal reported. Furthermore, panel members were concerned about the possible risk of heart attacks in knee surgery patients using the drug on a short-term basis.

They suggested more data are needed to support the approval of the drug, AstraZeneca said in a press release.

Company officials expect a final FDA decision near the end of October, Reuters reported.

AstraZeneca shares closed at $43.74, down $0.66, or 1.5 percent, in heavy trading on the New York Stock Exchange.

September 10, 2004

FDA STAFF REPORT RAISES CONCERNS OF LIVER DAMAGE ASSOCIATED WITH ASTRAZENECA'S EXANTA

A Food and Drug Administration staff report released Thursday raised significant concerns regarding potential liver damage associated with long-term use of AstraZeneca Plc's Exanta (ximelagatran).

The report was released one day prior to an FDA advisory committee meeting scheduled for today regarding the therapy.

Dr. Tim Anderson, analyst for Prudential Equity Group, said in a research note that the staff report's safety and efficacy documents "look downright bad," according to TheStreet.com

"Prior to seeing the documents, we had forecasted odds of approval at 60/40. The odds may now be lower," he cautioned.

The FDA report did not identify any risk of liver damage, which is measured by an increase in liver enzymes, during short-term use (less than 12 days) of Exanta, TheStreet.com report said.

Exanta is being evaluated for three indications: preventing blood clots in veins among patients undergoing knee replacement surgery, prophylaxis of stroke and other clot-induced complications associated with atrial fibrillation and long-term prevention of blood clots in veins after a patient has received a standard blood clot treatment.

AstraZeneca shares closed at $44.40, down $2.65, or 5.6 percent, in heavy trading on the New York Stock Exchange.

July 17, 2003 

LIVER FUNCTION TESTING MAY BE REQUIRED FOR PATIENTS ADMINISTERED EXANTA, ASTRAZENECA SAYS

AstraZeneca Plc said it expects that patients who receive the company's investigational anticoagulant Exanta (ximelagatran) will be required to undergo liver function testing to monitor toxicity levels, according to a Reuters report.

AstraZeneca, however, said it believes the extent of liver toxicity monitoring would be much less than is required with currently approved anticoagulants such as warfarin.

Earlier this week, the pharmaceutical firm released trial data that indicated 9.6 percent of patients administered Exanta had elevated liver enzyme levels compared with 2 percent of patients receiving other anticoagulants.

Specifically, AstraZeneca said that enzyme levels rose in a predictable manner to three times the upper limit of normal range after the first two or three months of Exanta therapy. Liver enzyme levels then returned to normal within a similar period, regardless of whether Exanta therapy was halted; monitoring of patients on warfarin must continue for as long as the patient is receiving the drug.

Analysts at Goldman Sachs said the liver safety concerns could result in a "prolonged" review process for Exanta in the United States. They also noted that the necessity of monitoring liver enzyme levels would reduce one of the advantages of Exanta over warfarin.

July 15, 2003

EXANTA AS EFFECTIVE AS STANDARD CARE FOR ACUTE VENOUS THROMBOEMBOLISM, STUDY SHOWS

According to a new study, AstraZeneca Plc's Exanta (ximelagatran), intended to treat acute venous thromboembolism, is as effective as Aventis SA's Lovenox (enoxaparin) plus warfarin, the current standard of care for venous thromboembolism.

The study data, presented in Birmingham, United Kingdom, at the 19th Congress of the International Society on Thrombosis and Hemostasis, also showed a "favorable trend" for Exanta in bleeding and mortality rates as compared with standard therapy.

In the trial, patients were randomly assigned to receive either a 36-mg dose of Exanta twice daily or the standard treatment of 1 mg of Lovenox per kilogram of body weight followed by dose-adjusted warfarin.

Results showed that there were 26 events of recurrent venous thromboembolism in patients treated with Exanta compared with 24 events found in those patients who received Lovenox plus warfarin.

Safety and mortality outcomes also showed a favorable trend for Exanta over standard treatment with respect to the risk of major bleeding; there were 14 events in the Exanta group versus 25 events in the standard treatment group.

Exanta is the first anticoagulant to reach late-stage trials since warfarin was developed nearly 50 years ago, according to AstraZeneca.