APM Health Europe: Healthcare Business News for European Pharmaceutical Markets

By Ailis Kane

LONDON, July 27 (APM) - New concerns over the safety of GlaxoSmithKline's thiazolidinedione Avandia and Takeda's similar antidiabetic Actos have emerged just days before a panel of experts in the U.S. meets to consider the safety of Avandia.

New results published in the August edition of the journal Diabetes Care and released on Friday suggest that the known side effect of heart failure with Avandia (rosiglitazone) and Actos (pioglitazone) could effect a broader group of patients and at lower doses than originally thought.

Co-author and renowned safety critic Dr Curt Furberg of Wake Forest University School of Medicine's Division of Public Health Sciences in North Carolina said in a statement: "Our findings support current efforts by the [U.S. Food and Drug Administration] to add a black-box warning to the labelling for these agents."

The researchers conducted a meta-analysis of trials of Avandia and Actos and found the drugs doubled the risk of heart failure, which was seen in patients without prior heart failure and at low doses. The "number needed to harm" with the drugs was 50 patients over 2.2 years.

"These drugs are taken by more than seven million diabetic patients in the U.S. alone, suggesting that several thousand could be harmed," said another author Dr Sonal Sing, also of the Wake Forest University School of Medicine.

EMEA AND NICE SHOULD RE-THINK

The third author Dr Yoon Loke from England's University of East Anglia School of Medicine, Health Policy and Practice unit, told APM he had emailed the EMEA to inform the agency that the data was being released.

He also called for NICE to reconsider its decision to recommend the use of the drugs by the UK's National Health Service, in light of the new data and recent findings suggesting Actos had little positive effect on clinical outcomes.

In addition, Furberg will detail the results to the U.S. Food and Drug Administration (FDA) at a joint meeting of the endocrinologic and metabolic drugs advisory and the drug safety and risk management advisory committees on Monday, said Loke. Furberg is well-known for speaking out on drug safety issues.

The FDA meeting was called to discuss the cardiovascular safety of Avandia after a study in the New England Journal of Medicine showed a possible link between the drug and an increase in myocardial infarctions and cardiac death. Furberg wrote an editorial accompanying the NEJM paper in June.

NEW META-ANALYSIS

The new meta-analysis looked at clinical trials of Avandia and Actos in a total of 78,000 patients.

In the data from randomised controlled trials, Singh, Loke and Furberg found the pooled odds ratio for heart failure in glitazone users was 2.1 and for data from observational studies it was 1.55.

The Avandia package insert warns against its use in patient with NYHA stage III and IV heart failure and cautions about the increased risk of heart failure in combination with insulin.

However, in the meta-analysis the increased risk was not confined to patients on insulin.

Advice by the American Heart Association and the American Diabetes Association recommends that the drugs can be used in patients with less severe NYHA stage I and II heart failure if they are started at a low dose, slowly increased and closely monitored.

But again, the meta-analysis results appeared to contradict this advice. "Recommendations for their use even at low doses in NYHA stage I and II patients, and in those with risk factors for heart failure may need to be carefully re-evaluated as heart failure occurred even among patients with no history of heart failure ... [and at] the lowest dose range in spontaneous reports and at both the low (4mg) and high (8mg) doses of rosiglitazone used in clinical trials," the authors write.

In addition, the results suggest the side-effect is not always easy to detect in the short term. Singh said: "The occurence of heart failure several months after initiation of treatment suggests a long-term effect of the drugs, which may not be avoided by beginning with low doses."

However, they do acknowledge a number of limitations with the study including that the diagnosis of heart failure is challenging and sometimes subjective, inconsistencies in diagnostic criteria across studies, the possibility of unrepresentative anecdotal reports and other sources of bias.

The researchers called for further research into the intra-class differences in the risk of heart failure and the best way to manage heart failure in these patients.

The researchers say that the development of heart failure appears to be a class effect of the thiazolidinediones, because of their effect increasing oedema.

"Fluid retention due to thiazolidinediones may trigger clinically apparent episodes of heart failure in susceptible individuals or may unveil the disease in those with latent heart failure," they suggest.

CALL TO NICE TO RE-VISIT GUIDANCE

Loke said in an interview with APM he would not be prescribing either Avandia or Actos for his patients.

He said that NICE should look again at the cost-effectiveness of the drugs, taking into account the extra cost of treating patients with heart failure and the fact that a systematic review of the class by the Cochrane group in 2006 found little evidence that Actos had a beneficial effect on hard clinical endpoints.

He said that the use of thiazolidinediones in the UK had doubled from 0.75 million prescriptions in 2003, before NICE guidance on their use, to 1.5 million in 2006. The products had sales of 70 million pounds.

"I don't think this is a cost effective use of NHS resources ... They don't seem to be beneficial to patients.

"It is creating a much greater burden for the NHS with this data. NICE need to go back and review the advice."

(Diabetes Care, August, vol. 30, no. 8.)

ak/ns

ailis.kane@apmnews.com
[7635] 27/07/2007 00:01 GMT - DIABETE

PARIS, July 27 (APM) - Gilead's nucleoside analogue combination Truvada (emtricitabine + tenofovir) has similar virologic efficacy to GlaxoSmithKline's Kivexa (lamivudine + abacavir) but a better effect on lipids, according to a study presented at the international AIDS conference in Sydney.

These two antiretroviral combinations are amongst the most widely used in HIV but had never been compared in a trial, said Jose Gatell, from the Hospital Clinic Universitari in Barcelona at his Wednesday presentation.

In the BICOMBO trial, he randomised 335 patients who had been on a lamivudine-based regimen for at least six months between two groups. One group was treated with Kivexa and the other with Truvada, as the nucleoside element of a regimen also including either a non-nucleoside analogue or a protease inhibitor.

At 48 weeks, more patients had treatment failure (viral load above 200 copies/mL, discontinuation, AIDS-defining event, death) with Kivexa than with Truvada, at 19% vs 13%.

The researchers said this significant difference was mainly due to hypersensitivity to abacavir, suspected in 5% of Kivexa patients.

When only virologic failure was taken into account - viral load above 200 copies/mL - the difference became negligible at 2.4% with Kivexa and 0% with Truvada.

Immunological results were better with Kivexa, with a 44 cell/mm3 increase of CD4 counts compared to a 2.7 cell/mm3 reduction with Truvada.

There were more adverse effects in the Kivexa arm (65%) than in the Truvada arm (54%).

Truvada was also linked to better lipid outcomes, with reductions in total cholesterol and LDL-cholesterol (-9 and -4 mg/L), which rose with Kivexa (+12 and +7 mg/L). The only exception was HDL-cholesterol which decreased with Truvada (-4 mg/L) and remained stable with Kivexa.

Triglyceride levels decreased with Truvada (-16 mg/L) but did not change with Kivexa.

There was no significant difference between the two products in terms of renal function or bone mineral density.

rl/cd/clg/ns

romain.loury@apmnews.com
[7636] 27/07/2007 05:00 GMT - AIDS

PARIS, July 27 (APM) - A combination of Alcon's Travatan (travoprost) and Alcon's Azopt (brinzolamide) is more effective than Travatan with Allergan's Alphagan (brimonidine) in lowering intraocular pressure in glaucoma, according to an Alcon financed comparative study.

When a prostaglandin analogue is insufficient to decrease intraocular pressure, a second agent is added.

Dr Robert Feldman from the University of Texas in Houston and colleagues report results from a comparison between Azopt and Alphagan, added to monotherapy with Travatan. The study was carried out in 163 patients with primary open-angle glaucoma, exfoliation glaucoma or ocular hypertension.

Brinzolamide 1%, a carbionic anhydrase inhibitor, or brimonidine 0.15%, a selective alpha-2-adrenergic receptor agonist, was administered twice daily.

There was a greater reduction in diurnal intraocular pressure at three months with travoprost-brinzolamide (significant difference of 0.7 mmHg). At three months, intraocular pressure was 18.6 mmHg with brinzolamide and 19.3 mmHg with brimonidine.

However, the researchers say the clinical relevance of this difference was uncertain as, although it was a statistically significant difference, it was nevertheless small.

The researchers note that the difference was greater in certain patients than in others.

(Ophthalmology volume 114 number 7, pages 1248-54)

sl/clg/ns

sylvie.lapostolle@apmnews.com
[7637] 27/07/2007 05:00 GMT - NEURO

MILAN, July 27 (APM) - Recordati has reported a 20.1% rise in first-half net income on the back of 10.8% growth in international sales.

Sales in Italy fell by 9.8% to 105.8 million euros as a result of obligatory price cuts introduced in 2006 and increased generic competition.

The Italian group in a statement on Thursday said it had 320.5 million euros of revenues in the first six months of 2007, 3% higher than the same period last year. Pharmaceutical revenues amounted to 301 million euros.

"The significant contribution of our international business, which now accounts for two thirds of sales, continues to be fundamental for the development of the group," Giovanni Recordati, chairman and CEO, said.

Operating income rose 9.5% to 69.6 million euros while net income was 20.1% higher at 44.9 million euros. Earnings before interest and taxes (EBIT) were up 9.5% at 69.6 million euros.

RECORDATI CONFIRMS 2007 GUIDANCE

Fritz Squindo, Recordati's CFO, was cautiously optimistic about expectations for the full year during a conference call on Thursday. He confirmed the full-year guidance given in February.

Recordati forecast 650 million euros revenues, earnings before interest and tax (EBIT) at 132 million euros and net income at 83 million euros for the whole of 2007.

Squindo said that improved margins in the first half meant that the company anticipates little problem in meeting the EBIT target.

Gross profit at 217.1 million euros was 67.8% of revenues compared to 67.1% in the first half of 2006.

It may be a little more difficult for Recordati to meet its revenue target for the full year, Squindo said.

LERCANIDIPINE SALES NETWORK EXPANDED

Recordati has expanded the direct sales network of Zanidip (lercanidipine), its proprietary calcium channel blocker.

Direct marketing of the drug has started in Ireland and in Greece, where it is known as Lercadip.

In France sales of lerrcanidipine were up 20.3% at 20.8 million euros while in the UK they jumped 23.6% to 5.7 million.

ROLL OUT OF ZANIPRESS IN 2008

Next year, Recordati will start rolling out Zanipress, a lercanidipine/enapril fixed combination. Last year, it was approved in Germany as the reference member state in the EU's mutual recognition approval process.

Recordati expects it to be approved in all other EU countries by year-end.

Squindo said he expects the UK to be the next market where Zanipress is launched as it is rolled out across Europe in 2008.

In Germany Zanipress went on the market in April. Squindo forecast that it will have sales of between 1-1.5 million euros by the end of the year.

rg/nh

robert.galbraith@apmnews.com
[7638] 27/07/2007 06:12 GMT - INDUSTRY

MADRID, July 27 (APM) - Spain's Faes Farma reported on Friday a 12.5% rise in first-half net profits to 12.9 million euros.

In a brief statement, the Bilbao-based company said that net sales were 99.1 million euros, representing a very slight increase of 0.4% compared to January-June 2006, "in spite of the strong price reductions suffered these last years in the national market and in Portugal.

"This negative effect, which entirely affects operating accounts, EBIT (earnings before interest and tax) and EBITDA (earnings before interest tax and amortisation), has been compensated thanks to the effort made in exports and OTC," the statement said.

Faes Farma, Spain's third-largest home-grown pharma, predicted a significant increase in future revenues from its blockbuster oral anti-histamine compound bilastine.

Last year, the company signed a licensing agreement for bilastine in North America potentially worth $89 million and negotiations continue on licensing agreements for bilastine in Europe, Asia and Latin America.

bj/nh

benjamin.jones@apmnews.com
[7639] 27/07/2007 07:20 GMT - INDUSTRY

LONDON, July 27 (APM) - Amgen has reported a 3% rise in revenue to $3.73 billion despite falling sales of Aranesp over the second quarter which CEO Kevin Sharer described as a "difficult period".

The California-based company in a statement issued late on Thursday said its outlook for 2007 2007 could be blown off course by two key events, although at the moment current sales and expense trends are consistent with an adjusted earnings per share (EPS) target of $4.30.

"However, the recent acquisitions of Alantos and Ilypsa are expected to reduce adjusted EPS by 2 cents, to $4.28.

"The outcome of key events... may affect the outlook for full-year 2007, and the company will provide updates as appropriate," said Amgen citing two upcoming decision points that could effect Aranesp.

Firstly, the Centers for Medicare & Medicaid Services is currently reviewing the National Coverage Determination for erythropoiesis stimulating agents (ESAs) such as Aranesp to determine whether they can be covered under the federal medical insurance programmes Medicare and Medicaid for non-renal uses.

Secondly, the Food and Drug Administration's Cardiovascular and Renal Drugs Advisory Committee (CRDAC) is meeting in September to review the use of ESAs in the treatment of renal anaemia, after recent safety concerns.

For the second quarter, Amgen said that on a GAAP basis (Generally Accepted Accounting Principles), net income climbed to $1.02 billion compared with $14 million a year ago, when profits were hit by a $1.1 billion charge relating to its Abgenix acquisition.

Diluted EPS improved from 1 cent a year ago to $0.90. R&D expenditure rose from $788 million to $817 million.

"This has been a difficult period and this quarter's low growth is a reflection of that reality," said Kevin Sharer, chairman & CEO.

"That said, we are making progress on many fronts to change this trend and return Amgen to strong future performance."

SALES PERFORMANCE

During the second quarter, total product sales increased 3% to $3.6 billion. Sales in the U.S. edged ahead 1% to $2.9 billion.

International sales increased 15% to $725 million. Changes in foreign exchange positively impacted second quarter 2007 international sales by $41 million. Excluding the impact of foreign exchange, total product sales increased 2% and international product sales increased 9%.

Worldwide sales of Aranesp (darbepoetin alfa) fell by 10% to $949 million, mainly because of a decline in U.S. demand.

U.S. Aranesp sales slumped by 19% to $578 million, "reflecting customer reaction to label and reimbursement changes and to a lesser degree unfavorable wholesaler inventory changes offset by end-user inventory build". In March, Aranesp and other EPOs were subject to a new black box warning in the U.S. to warn of side effects.

International Aranesp sales increased by 8% to $371 million, primarily due to changes in foreign exchange which positively impacted sales by approximately $21 million.

In Europe, growth due to increased demand in the nephrology segment was partially offset by "slight dosing conservatism" in the oncology segment. Excluding the impact of foreign exchange, worldwide product sales decreased 12% and international sales increased by 2%.

Sales of Epogen (epoetin alfa) increased 2% percent to $624 million, while worldwide sales of Neulasta (pegfilgrastim) and Neupogen (filgrastim), increased 4% to $1.04 billion, driven primarily by increased international demand for Neulasta.

Combined sales of Neulasta and Neupogen in the U.S. slipped 2% to $773 million, reflecting
unfavorable wholesaler inventory changes and increased discounts.

Combined international sales increased 22% to $268 million, reflecting both the continued conversion to Neulasta (from Neupogen) and changes in foreign exchange which positively impacted second quarter 2007 combined international sales by approximately $16 million.

Excluding the impact of foreign exchange, combined worldwide sales increased 2% and international product sales increased 15%.

Sales of the anti-TNF Enbrel (etanercept) increased 14% to $823 million, reflecting an increase in demand due to increases in both patients and net sales price. Sales growth continued in both rheumatology and dermatology.

Worldwide sales of its blood calcium lowerer Sensipar (cinacalcet HCl) increased 37% to $108 million.

Vectibix (panitumumab) sales declined by $6 million to $45 million because of reaction to unfavorable PACCE study results released late in the first quarter of 2007 and a decline in EGFr class growth in metastatic colorectal cancer.

PIPELINE UPDATE

Enrolment has begun in the company's Phase III study to evaluate Vectibix in the treatment of patients with metastatic and/or recurrent squamous cell cancer of the head and neck.

Amgen expects to enroll approximately 650 patients in this study. The primary endpoint is overall survival, with secondary endpoints of progression-free survival, overall response rate, time to progression, duration of response and safety.

Enrolment has begun in the company's Phase III study to evaluate motesanib diphosphate, a multi-targeted VEGF inhibitor, in the treatment of patients with advanced non-small cell lung cancer.

Amgen said it expects to enrol approximately 1,250 patients in this study. The primary endpoint is overall survival, with secondary endpoints of tumor response rate, duration of response and progression-free survival.

nh/ak

nick.hudson@apmnews.com
[7640] 27/07/2007 07:38 GMT - INDUSTRY

MILAN, July 27 (APM) - Italy's MolMed is considering a public listing in Milan or Zurich although its shareholders remain divided about the options, according to a press report.

Italy's business weekly, Il Mondo, reported on Friday that the Milan-based biotech is close to choosing a bank to be global coordinator of the deal. It estimated the company could be worth between 250-300 million euros.

The chairman and general manager of its largest shareholder, Science Park Raf, a company linked to the Milan hospital San Raffaele, are said to be in favour of a float.

But its most illustrious shareholder, Fininvest, the company owned by the family of former prime minister Silvio Berlusconi, was reported to be against the idea. It owns 21.8% of MolMed and is the second largest investor.

"If more money is required to finance the pipeline, the Berlusconi family would do its part and expect to see its investment to appreciate in value significantly," Il Mondo said.

So far shareholders have invested 66 million euros and another 10 million could be put in by October, the magazine reported.

MolMed is one of several pharma projects to have emerged from the biotechnology department at the San Raffaele hospital in Milan.

THREE POTENTIAL CANCER TREATMENTS

MolMed has three projects in Phase II trials, all potential cancer treatments.

TK, the most advanced, is a cell therapy being developed to allow safe haploidentical haematopoietic stem cell transplantation (HSCT) during the treatment of haematological malignancies (leukaemias, lymphomas and myelomas).

MolMed successfully completed a Phase I/II multicentric clinical trial in Europe for patients with high-risk acute leukaemia.

Orphan drug designation for TK has been granted in the EU and in the U.S.

M3TK is a cancer therapeutic vaccine for solid tumours. MolMed is conducting a Phase I/II clinical trial for the treatment of melanoma.

Arenegyr is a vascular targeting agent which selectively binds to and acts on tumour blood vessels.

Phase II trials of single agent. low-dose Arenegyr are ongoing in colorectal cancer, hepatocarcinoma. small-cell lung carcinoma and mesothelioma.

rg/nh

robert.galbraith@apmnews.com
[7641] 27/07/2007 08:46 GMT - INDUSTRY

BERLIN, July 27 (APM) - German statutory health insurers are asking for measures to encourage competition in patent medicines pricing, following those taken for generic drugs under the AVWG and WSG reforms.

In the first half of 2007, total sales of patent-protected drugs in Germany rose 13.7% to 3.9 billion euros (ex-manufacturer price) compared to 1.1% in the German pharmaceuticals market as a whole, according to a press release from German pharmaceutical statistics group Insight Health.

"Legislators should no longer accept that the prices of new patent-protected medicines are unilaterally fixed by the pharmaceutical industry," said Ingo Kailuweit, director of insurers KKH. This procedure allows the industry to make money at the expense of patients, which "must stop".

In Germany, the price of patented medicines is fixed by manufacturers and controlled by the German health ministry by reimbursement capping (Festbetrag) or by assessment of the product's benefit by the Institute for Quality and Efficiency in Healthcare (IQWiG), a health technology assessment body. The level of control depends on how innovative the treatment is.

Johannes Vöcking, head of Barmer health insurers, goes even further in a press release claiming that "pharma locusts are destroying Germany".

Christopher Hermann, vice-chairman of local health insurers AOK, recently told APM he was looking at the possibility of extending the model of preferential pricing for generic medicines to cover branded medicines too.

In February, the AOK signed preferential price deals for 43 products, and they are now about to launch a second round of calls to tender for agreements on 82 products.

35% OF PHARMA SALES FOR PATENTED DRUGS

Patent-protected drugs now account for 35.1% of the total German pharmaceuticals market, slightly more than off-patent medicines which have 34%, said Insight Health.

Vaccine sales were up 136%, fuelled by Sanofi-Aventis' cervical cancer vaccine Gardasil, Wyeth's Prevenar against otitis due to pneumococcal infections and meningococcal vaccines from Sanofi-Aventis, Chiron (Novartis group) and Wyeth.

Sales of leukaemia drugs Bayer Schering Pharma's MabCampath (alemtuzumab) and Roche's MabThera (rituximab) grew by 47.9%, Merck & Co's lipid lowerer Inegy (ezetimibe and simvastatin) by 23.3% and attention deficit hyperactivity disorder drugs Lilly's Strattera (atomoxetine) and Janssen Cilag's Concerta (extended release methylphenidate) by 23.2%.

Generic sales were down 9.8% to 2.6 billion euros (ex-manufacturer price) despite a 1.8% rise in volumes sold.

Off-patent drugs targeted by generic competition were down 19.9% to 1.3 billion euros, 11.4% of the total pharmaceutical market, showing the growing impact of generic products.

However, sales of off-patent drugs with no generic equivalent, such as vaccines and human insulin, rose 8.1% to 3.4 billion euros.

Changes in the market for drugs which can be produced generically shows the competition sparked off by the AVWG and WSG reforms, the insurers believe.

Under the AVWG reform of May 2006, health insurers can release clients from formerly obligatory copayments if they accept a drug whose price is at least 30% lower than the maximum reimbursement rate (Festbetrag). The copayment is 10% of the price of a medicine, with a minimum of 5 euros and a maximum of 10.

Under the WSG reform of April 2007, only health insurers can make preferential price deals with manufacturers.

Unlike generics, the choice between branded drugs is generally limited to a few brands. This makes cooperation agreements with health insurers practically impossible due to risks of unfair competition and monopolies.

GROWTH ONLY DUE TO INCREASING NEED?

There is no cause for alarm at the growth in the German pharmaceuticals, as it only shows progress in treating therapeutic needs which were previously unmet, says Bertram Häussler, head of the German institute for health and sociology research (IGES) and co-author of the Arzneimittel Atlas 2007 report.

The Arzneimittel Atlas is an analysis of the German pharmaceutical market drawn up for the association of research-based pharmaceutical companies (VFA).

The first Arzneimittel Atlas was presented in 2006 as an alternative to the pharmaceutical prescriptions report (AVR) which has been produced for 20 years by a team of pharmacologists at the demand of statutory health regime health insurers.

In its 2007 edition, the Arzneimittel Atlas says that in 2006, spending by German health insurers grew by 516 million euros, including 369 million euros for serious chronic diseases (cancer, rheumatoid arthritis, Crohn's disease, viral hepatitis), 200 million euros for vaccines and non-respiratory infections, 130 million euros for widespread chronic diseases (diabetes, hypertension) and 92 million euros for psychiatry.

These expenses were counterbalanced by reductions of 163 million euros in antibiotics for respiratory tract infections and 160 million in ulcer drugs.

A comparison using defined daily doses (DDD) shows that expenses are progressing at the same rate as DDD, said Häussler at a press conference on Thursday in Berlin to present the Arzneimittel Atlas 2007.

Health insurers were quick to respond to these claims, with the AOK scientific institute WIdO criticising the Arzneimittel's lack of scientific rigour.

The IGES report only takes into account certain kinds of medicines, and not the whole of the German pharmaceuticals market. And some extrapolations, notably concerning treatment duration, are arbitrary or based on surveys.

In 2005, pharmaceutical expenditure could have been reduced by 1.3 billion euros by systematically substituting generic products for off-patented branded medicines, the AVR says.

"These savings can be carried out without lowering healthcare standards. But such figures appear nowhere in the Arzneimittel Atlas," the WIdO says.

ap/clg/ak

arjen.peters@apmnews.com
[7642] 27/07/2007 08:55 GMT - INDUSTRY

LONDON, July 27 (APM) - Roche said it plans to launch its next-generation eyrthropoeitin product Mircera in the U.S. after regulatory approval, despite ongoing patent litigation with Amgen.

In a conference call to a small group of journalists on Thursday, Dan Kemmler, Roche's anaemia franchise director said: "Any where in the world we will launch the product independent of litigation."

He also indicated that Roche did not expect biosimilar EPOs to have a large impact on Mircera.

He was speaking after the company announced that Mircera had gained final EU approval for anaemia related to chronic kidney disease.

Until now, Roche has not launched an epoetin in the U.S, but it hopes to be able to with Mircera.

The product received an approvable letter from the U.S. Food and Drug Administration in May. Kemmler said that Roche was very confident it would gain approval after the conclusion of an FDA advisory panel on the use of EPOs (excluding Mircera) in renal anaemia.

BIOSIMILAR IMPACT

Biosimilar EPOs are another potential hazard for Mircera, especially in Europe after the CHMP recommended approval for three epoetin alfa products from Sandoz, Hexal and Medice Arzneimittel Putter in late June.

However, despite analysts' warning to the contrary, Kemmler believes Mircera and its existing EPO in Europe NeoRecormon (epoetin beta) will feel little impact from generic competition. "We don't see a huge threat to Mircera."

He expects sales of epoetin alfa products to suffer most from the generics, because these are the reference products.

In addition, he said that while the CHMP had given a positive recommendation, it could be some time before the drugs are launched in Europe.

Kemmler reiterated his belief that Mircera would "rapidly become the market leader" in markets where Roche's anaemia franchise already has a strong hold.

He said Roche would launch Mircera "almost immediately" in the UK and Germany following full approval. The company hopes to launch the drug in Scandinavia and the Benelux countries by the end of the year or early 2008, with roll-out in other markets including Spain, France and Italy following in 2008.

CANCER INDICATION STILL A POSSIBILITY

Roche was still committed to developing Mircera for cancer-related anaemia, said Kemmler, after it stopped a Phase II trial in lung cancer patients in the second quarter of this year because of an "imbalance in outcomes in the different treatment groups".

That imbalance was not due to either patients' haemoglobin levels or the use of Mircera in the trial, said Kemmler.

Roche would base future studies on advice from the FDA, he said. The agency had not yet put out final guidance on the issue, but had heard evidence from its oncologic drugs advisory committee in May.

ak/nh

ailis.kane@apmnews.com
[7643] 27/07/2007 09:28 GMT - INDUSTRY

Next week:

# July 30, GSK's Avandia - joint meeting of FDA's Endocrinologic & Metabolic Drugs and Drug Safety and Risk Management Advisory Committees.

# July 31, Paion Q2

# July 31, FDA panels review Elan's Tysabri for the treatment of Crohn's disease

# Aug 1, Sanofi-aventis + Teva + Allergan + DeCode Genetics Q2

# Aug 3, Novo Nordisk Q2

Following weeks:

# Aug 7, Bayer Q2

# Aug 9, Bavarian Nordic Q2

# Aug 10, UK court ruling on whether NICE assessed Alzheimer drugs fairly

# Aug 12, FDA action date for Lundbeck/Wyeth's bifeprunox

# Aug 15, Lundbeck + Speedel Q2

# Aug 16, CHMP

# Aug 23 Basilea Q2

# Aug 31, Acambis PDUFA date for ACAM2000

# Sept 1, Acambis Q2

# Sept 1 - 5, European Society of Cardiology, Vienna

# Sept 15 - 19, European Respiratory Society, Stockholm

# Sept 17, Sanofi-aventis R&D meeting, Paris

# Sept 17 - 20, Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago

# Sept 17 - 21, European Association for the Study of Diabetes, Amsterdam

# Sept 20, SkyePharma Q2

# Sept 23 -27, ECCO 14 European cancer conference, Barcelona

# Oct 4 - 6, EUROGIN 2007, strategies of cervical cancer prevention (the reality of HPV Vaccines), Monaco

# Oct 11 - 14, European Committee for Treatment & Research in Multiple Sclerosis, Prague

# Oct 31 - Nov 5, American Society of Nephrology, San Francisco

# Nov 4 - 7, American Heart Association, Orlando

# Nov 6 - 11, American College of Rheumatology, Boston

# Nov 9 -14, American College of Allergy Asthma & Immunology, Dallas

# Dec 8 - 11, American Society of Hematology, Atlanta

# Dec 13 - 16, San Antonio Breast Cancer Symposium, Texas

nh/

editorial@apmnews.com
[7644] 27/07/2007 10:26 GMT - INDUSTRY

BRUSSELS, July 27 (APM) - Solvay's second-quarter earnings in its pharma division tumbled as sales fell 3% to 627 million euros, the Belgian, chemicals, plastics and pharma group reported on Friday.

It said in a statement that its pharma division's recurring earnings before interest and tax (REBIT) plunged 32% to 81 million euros compared with the year-ago quarter.

In the first half, pharma REBIT fell 16% to 205 million euros, with sales down 5% to 1.25 billion euros.

CHANGE AND PRICE PRESSURES

Solvay said its pharma results were affected by the negative impact of the dollar/euro exchange rate, which cut 3% from sales.

Other factors affecting the results were the expiry of the patent on ulcer drug Pantoloc (pantoprazole) and pricing pressures in Europe, especially in France.

These negative effects were partially compensated by a rise in sales of other products and the "Inspire" savings plan which is continuing as planned, Solvay added.

Inspire is a restructuring plan for the group's pharmaceuticals division, with which Solvay aims to achieve over 7% sales growth per year and operating margins of 20% by 2010.

The pharma results impacted the group's overall results, which show a 3% rise in REBIT in the first half to 616 million euros, with sales up 1% to 4.8 billion euros.

Solvay's other two divisions performed better, with a 10% rise in chemicals REBIT in the first half to 189 million euros and a 13% rise in plastics REBIT to 245 million.

For the whole year 2007, the Belgian group confirmed it can achieve the same operating results as last year.

It expects pharmaceuticals' sales to stabilise. Solvay is looking to achieve annual cost savings in the pharma division of 300 million euros in 2010, with the help of restructuring.

FENOFIBRATE SALES DOWN 9%

By therapeutic class over the first half, sales of cardiometabolics were down 2% (+1% at constant exchange rates) to 362 million euros, while fenofibrate (Lipanthyl, Tricor) sales fell 9% (-4% at constant exchange rates) at 209 million.

Solvay said it is continuing to develop successors for Lipanthyl/TriCor, including a new generation fenofibrate developed with Abbott, ABT335/SLV348, which is currently in Phase III.

The Belgian group said it intends to file this product in the U.S. in the second half of 2007.

The group also said that AstraZeneca and Abbott still intend to file for U.S. authorisation in 2009 for a fixed combination of AZN's statin Crestor (rosuvastatin) with eitherTriCor 145 NFE or the new generation fenofibrate developed with Abbott.

Sales of antihypertensive Teveten (eprosartan) increased by 11% to 52 million euros during the first half of the year.

Neuroscience was up 2% (6% without currency effects) to 229 million euros, whilst flu vaccines lost 8% to 22 million euros, with Influvac sales tumbling 42% (43% without currency effects) to 7 million euros.

As far as vaccines are concerned, Solvay said its new site in the Netherlands for producing flu vaccines using cell technology should start producing prepandemic vaccines for various governments at the end of 2007, along with vaccines for clinical trials. Marketing is planned for 2008.

The statement showed pancreatic enzymes (Creon) stagnated at 96 million euros.

Gastroenterology was down 38% (37% at constant exchange rates) to 116 million euros, whilst gynaecology-andrology gained 3% (9% at constant exchange rates) at 319 millioneuros, with a 13% progression (23% without currency effects) for Androgel (testosterone) to 160 million.

Sales of hormone substitution treatment Prometrium (progesterone) stagnated (but grew 9% without currency effects) at 40 million euros.

pw/clg/nh

philippe.wackel@apmnews.com
[7645] 27/07/2007 10:28 GMT - INDUSTRY

LONDON, July 27 (APM) - GlaxoSmithKline on Friday announced it has signed a deal with Targacept to discover, develop and market novel therapeutics that selectively target specified neuronal nicotinic receptors (NNRs).

In a joint statement, GSK said the deal was worth up to $1.5 billion plus tiered double digit royalties to the U.S. biotech.

However, in the tie-up that leaves Targacept carrying much responsibility in the hope of a potentially huge later payback, GSK's initial investment is just $35 million, including purchasing $15 million of Targacept stock.

The partnership gives the UK giant the rights to Targacept's lead candidate TC-2696, which is currently in Phase II for acute post-operative pain.

It also includes the preclinical, TC-6499, which is under development for neuropathic pain as well as access to other discovery programmes in a further four therapeutic areas.

In addition to pain, the other therapeutic focus areas of the alliance are smoking cessation, obesity, addiction and Parkinson's disease.

Targacept has retained an option to co-promote TC-2696 and TC-6499 for pain to specialists and hospital-based physicians in its home market, GSK added.

PENTAD

Under the terms of the agreement, Targacept will utilise its proprietary Pentad drug discovery technology to discover novel, small molecule product candidates that target specified NNR subtypes.

It will then develop the most promising candidate for each target therapeutic area through a Phase II proof of concept trial.

Upon Targacept's achievement of clinical proof of concept for a lead candidate for a particular therapeutic area, GSK would have an exclusive option to license the candidate.

After successful Phase II proof of concept, GSK will assume full responsibility for funding of further clinical development and commercialisation on a worldwide basis.

CEEDD

Quoted in the joint statement J Donald deBethizy, president and CEO of Targacept, said the breadth of the alliance validated the importance of NNRs in the potential treatment of a broad range of CNS-related disorders and allowed Targacept to expedite its research programme.

"This uniquely structured deal enables us to accelerate the progression of our pipeline, capitalise on our discovery and development expertise and leverage the resources of a premier global pharmaceutical company while retaining considerable value," he said.

GSK will participate in the alliance through its CEEDD - Centre of Excellence for External Drug Discovery - unit, which focuses on making external agreements with biotechs which retain responsibility to provide proof of concept.

Also in the statement, Hugh Cowley, senior vice president and head of CEEDD said: "This alliance provides us access to innovative science and pioneering research and expertise in the promising NNR field. We believe there is tremendous potential for NNR therapeutics for a variety of CNS-related diseases and disorders."

ASTRAZENECA'S MEMORY LOSS

Targacept already has an agreement in place with Britain's AstraZeneca. In May 2006, the biotech announced statistically significant results in all three primary end points of a Phase II trial of TC-1734 (AZD3480) in memory loss.

AZN licensed TC-1734, which is designed to act on neuronal nicotinic acetylcholine receptors which regulate brain and nervous system functions, in a December 2005 deal worth up to $300 million in milestone and other payments plus stepped double digit royalties to Targacept.

ns/nh

nick.smith@apmnews.com
[7646] 27/07/2007 13:05 GMT - NEURO

BERLIN, July 27 (APM) - Altana played down on Friday the significance of two legal actions launched by shareholders against the way the company used the proceeds from the sale of its pharmaceutical business.

A company spokesman said a hearing was scheduled for October 2 at the Frankfurt district court for the suits brought in the names of individual shareholder Klaus Zapf and the firm Pomoschnik Rabotajet GmbH.

"We don't set any significance by these lawsuits. They will not have any effect on our business and they will not be successful," he told APM.

Altana sold the operations for 4.7 billion euros to financial investors, and half of the proceeds went to major shareholder Susanne Klatten, a member of the Quant family, the Financial Times Deutschland reported on Friday.

Large shareholders were able to obtain these proceeds tax-free, while smaller shareholders had to pay tax on them, the paper said.

At the shareholders' meetings in December and May, Altana shareholders raised this issue and complained that the sale was arranged to suit Klatten's needs.

"We dealt with the proceeds the same for big and small shareholders alike," the spokesman told APM. "What happened subsequently was not a matter for us."

vl/ak

vincent.landon@apmnews.com
[7647] 27/07/2007 13:27 GMT - GENERAL

LONDON, July 27 (APM) - The U.S. Food and Drug Administration (FDA) announced on Friday it was permitting the restricted use of Novartis's previously banned irritable bowel syndrome therapy, Zelnorm (tegaserod).

In a statement the FDA said the access was being granted under an investigational new drug (IND) protocol for the treatment of irritable bowel syndrome with constipation and chronic idiopathic constipation in women younger than 55 who meet specific guidelines.

The initiative comes some four months after Novartis pulled the drug in the U.S. on the request of the FDA, over fears it led to an increased risk of heart attack and strokes.

However, today the FDA explained that in some instances, patients with a serious or life-threatening disease or condition who are not enrolled in a clinical trial may be treated with a drug it had not approved.

Generally, such use is allowed within guidelines called a treatment IND, when no comparable or satisfactory alternative drug or therapy is available, it added.

ZELNORM'S TREATMENT IND

In addition to the age and gender restrictions, the IND protocol for Zelnorm limits use of the drug to those with IBS-C or CIC whose physicians decide the drug is medically necessary. Patients must sign consent materials to ensure they are fully informed of the potential risks and benefits of Zelnorm.

In the statement Steven Galson director of FDA's Center for Drug Evaluation and Research said: "These patients must meet strict criteria and have no known or pre-existing heart problems and be in critical need of this drug."

He added: "Zelnorm will remain off the market for general use."

According to FDA guidance, patients are considered to have chronic constipation if they have fewer than three complete spontaneous bowel movements per week and at least one of the following symptoms for at least 25% of those bowel movements: straining, hard stools, incomplete evacuation.

At one stage Zelnorm looked like a very promising drug and was just outside of Novartis's top-ten selling products, bringing in $561 million in 2006. However, $488 million of this was in the U.S. leading the Swiss company to downgrade its guidance when the drug was pulled from this market.

The EMEA finally rejected the drug in 2006.

ns/ak

nick.smith@apmnews.com
[7648] 27/07/2007 13:33 GMT - GASTRO