APM Health Europe: Healthcare Business News for European Pharmaceutical Markets

PARIS, August 7 (APM) - An international trial assessing the benefits of blood pressure-lowering medication in elderly hypertensive patients has been halted early after the strategy showed significant reductions in overall mortality, London's Imperial College announced on Tuesday.

The International Hypertension in the Very Elderly Trial (HYVET) compared treatment with Servier's diuretic Natrilix SR (indapamide) and ACE inhibitor Coversyl (perindopril) to reach target blood pressure of below 150/80 mmHg, with placebo in hypertensive patients aged over 80.

The risk/benefit ratio of treating hypertensive individuals over 80 years old had not previously been established. Whereas some trials had shown that antihypertensive treatment reduced stroke and cardiovascular events, other smaller and inconclusive studies had suggested that treatment did not reduce overall mortality and even increased it, Imperial College says in press release.

The trial, which received funding from the Institut de Recherches Internationales Servier, began in 2001 and would have ended in 2009.

"Preliminary results of the trial ... suggest that lowering blood pressure significantly reduces both stroke and mortality in the over-80s," says Imperial College.

On July 12, the HYVET steering committee accepted the recommendation of its data safety monitoring board that the trial be stopped.

Definitive figures will not be available until all the data has been collected, and results will then be published in the peer-reviewed scientific press, the press release says.

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carole.debray@apmnews.com
[7736] 07/08/2007 00:01 GMT - CARDIO NEURO

LONDON, Aug 7 (APM) - The global fibromyalgia drug market will quadruple to $2 billion by 2016, according to a report from market research group Decision Resources.

In its report on Monday, Decision Resources said the recent approval of Pfizer's Lyrica (pregabalin) for the musculoskeletal pain condition and the entry of several new drugs over the next decade will drive the fibromyalgia drug market.

Pharma companies have only recently begun to tap the market, mostly for secondary indications, it added. Treatment is characterised by polytherapy. "Most patients will be prescribed combinations of antidepressants, analgesics and/or sedative hypnotics."

New treatments that could be approved in the future include Lilly's Cymbalta (duloxetine), Cypress/Forest Lab's milnacipran, Wyeth's desvenlafaxine, Pfizer's Neurontin (gabapentin), UCB's (previously Schwarz Pharma's) lacosamide and Sepracor's Lunesta (eszopiclone).

The report predicts that the fibromyalgia market will "flourish" in the U.S, France, Germany, Italy, Spain, the UK and Japan.

STILL A LARGE OPPORTUNITY

However, the market will be constrained by the limited efficacy and tolerability of treatments.

Kate Hohenberg Decision Resources' director said in a statement that fibromyalgia is very difficult to treat.

"Even the leading new drugs for fibromyalgia will have drawbacks in efficacy and tolerability, and, as a result, there is still a large opportunity for drug developers," she added.

Fibromyalgia is a condition characterised by musculoskeletal pain with accompanying functional and sleep disorders. More than 14 million people in the world's major pharmaceutical markets are thought to have the condition.

"The vast majority of current cases are not diagnosed or treated by a physician, and even those who do receive drug therapy experience only modest relief," Decision Resources said.

ak/nh/ns

ailis.kane@apmnews.com
[7737] 07/08/2007 05:00 GMT - NEURO

PARIS, Aug 7 (APM) - Antiretrovirals are less toxic in patients co-infected with HIV and hepatitis C (HCV) once this disease has been successfully treated, a study published in the Journal of Infectious Diseases has shown.

Despite the improved hepatic tolerance of the new nucleoside analogues, there is an ongoing debate concerning the administration of antiretroviral drugs to co-infected patients before the hepatitis C has been treated, Curtis Cooper, from Ottawa hospital (Ontario) writes in an editorial.

On the one hand, hepatitis C, which affects 25% of French HIV-positive patients, increases the risk of antiretroviral-linked hepatotoxicity threefold but on the other hand HIV drugs slow the fibrosis rate and reduce the HCV viral load.

Pablo Labarga, from the Hospital Carlos III in Madrid, and colleagues reveal in their study with 132 co-infected patients treated with pegylated bitherapy that treating the hepatitis C first and only introducing the antiretrovirals subsequently, could enable the hepatotoxicity of these drugs to be reduced.

From among the 43 patients (33%) who obtained an extended virological response, only 9.3% had signs of hepatotoxicity with the HIV drugs - defined by grade 3-4 elevations in hepatic enzymes, potentially leading to an interruption of antiretrovirals - compared to 37.5% of those for whom the response to the HCV treatment was not as good, i.e. a risk of toxicity increased 6.13 fold.

This incidence of 9.3% is "comparable to that in patients who never had chronic viral hepatitis (8.3%)," a figure derived from a previous study, say the researchers.

The toxicity also depended on the HIV drugs used, with a 3.59-fold increased risk for BMS's Videx (didanosine) and Zerit (stavudine) or Boehringer-Ingelheim's Viramune (nevirapine). Conversely, the antiprotease-based regimens were linked to a 93% reduction in risk and this was 87% for antiretrovirals based on efavirenz (Sustiva, BMS).

The probability of hepatic events was twice as high among patients with advanced fibrosis (Metavir score F3 or F4), at 13.8% compared to 7.7%. The difference was not significant, which according to the researchers illustrates the fact that the "main determinant" of toxicity is not so much liver fibrosis itself but the ongoing damage linked to HCV replication.

"Successful treatment of chronic hepatitis C, besides preventing the development of end-stage liver disease, may reduce the risk of subsequent liver toxicity during antiretroviral therapy in HIV/HCV-coinfected patients," the researchers conclude. They consider this to be a further argument in favour of prioritising the treatment of hepatitis C.

Curtis Cooper qualifies these results, by saying that during his own research, "only 4% [of patients] abandoned or changed antiretroviral therapy as a direct consequence of liver-related complications".

Although they must be carefully monitored, "clinically relevant episodes are rare, and anxiety related to hepatotoxicity should not, as it often does, dissuade or delay patients and physicians from initiating liver-saving, and often life-saving, antiretroviral therapy".

According to the Canadian, who acknowledged that he first treated the HIV infection, the Spanish results could have limited application, due to the fact that co-infected patients commonly have low CD4 counts. "Such patients will need to receive HIV antiretroviral therapy first and take their chances with liver toxicity," he believes.

For those who present sooner, such as those in the study where the median CD4 count was 613 cells/mm3, it is then possible to follow the recommendations of the Spanish researchers, i.e. first treat the hepatitis in order to reduce the risk of toxicity when the HIV drugs are initiated.

"Only a minority of HIV/HCV-coinfected patients achieve a sustained virological response [6,15]," the risk of liver toxicity will remain unchanged for the others, says Curtis Cooper.

(Journal of Infectious Diseases, Vol. 196, No.5, p.670-676 and p. 656-658)

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romain.loury@apmnews.com
[7738] 07/08/2007 05:00 GMT - AIDS

PARIS, August 7 (APM) - French researchers have defined a new algorithm which can predict future non responders to HCV treatment among HIV/HCV coinfected patients as early as the fourth week of treatment.

Their results are published in August's edition of Gut and the researchers claims the potential financial savings of their algorithm, once verified as properly predictive, run into millions of euros.

In 2002, European and U.S. consensus conferences defined early virologic response to hepatitis C virus (HCV) treatment for patients with HCV or HCV/HIV alone by an undetectable viral load or a 2-log decrease, assessed at the 12th week of treatment, say Christopher Payan from Brest University Hospital and colleagues.

The French researchers wanted to assess the usefulness of measuring rapid virologic response in the second and fourth weeks of treatment, in 323 coinfected patients from the ANRS Ribavic trial - a published trial comparing Schering-Plough's pegylated interferon plus ribavirin to standard bitherapy with regular interferon and ribavirin.

They showed that the best positive predictive value of sustained virologic response (SVR) - an undetectable viral load six months after stopping treatment lasting 48 weeks - was obtained with an undetectable viral load at the fourth week (97%). The best negative predictive value was obtained with a reduction of more than 2 log at the 12th week (99%).

Prediction of non-SVR was obtained with patients using viral load cut-off levels above 460,000 international units (IU) per mL in the fourth week and above 39,000 IU/mL at the 12th week, irrespective of the HCV genotype and kind of treatment used (pegylated or standard bitherapy).

The researchers conclude that this new algorithm is useful: it can effectively predict future non-responders to treatment from the fourth week and would have saved about a million euros in treatment in the study - about 41%.

They however consider that this strategy needs confirming in other trials using coinfected patients and higher doses of ribavirin (1,000 to 1,200 mg/day compared with 800 mg/day in the Ribavic trial).

(Gut, August 2007, volume 56 number 8, pages 1111-6)

vdb/clg/ns

valerie.vandenbos@apmnews.com
[7739] 07/08/2007 06:00 GMT - AIDS

PARIS, Aug 7 (APM) - Bristol-Myers Squibb has written to opthalmologists after several serious cases of adverse events to draw their attention to the fact that its anti-inflammatory Kenacort Retard (injectable suspension of triamcinolone acetonide) does not carry any approved indication in ophthalmology.

In a letter published on Monday on the French Health Products Safety Agency's (Afssaps) internet site, BMS mentions "serious cases of endophthalmitis, ocular inflammation, increased intraocular pressure and visual difficulties including cases of blindness" following intravitreal administrations of the drug.

"Most of these cases have required treatment with drugs or surgery," BMS says.

In response to questions from APM, BMS France said that it was not able to give details of the number of cases reported.

The company emphasises that to date it has not carried out any studies to evaluate the drug's tolerance in subconjunctival, subtenonian, retrobulbar or intraocular administration.

It notes Kenacort Retard's indications in systemic use (intramuscular injection) in last-line treatment for seasonal allergic rhinitis and, in local use, in dermatology (intralesional injection) for cheloid scars and in rheumatology (intra-articular injections) in inflammatory arthritis and in episodes of arthrosis.

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edouard.hubert@apmnews.com
[7740] 07/08/2007 07:00 GMT - NEURO

BERLIN, Aug 7 (APM) - Bayer HealthCare has announced it is teaming up with Californian biotech Nektar Therapeutics to develop and market a treatment for Gram-negative pneumonias.

This new treatment method will utilise Nektar's proprietary pulmonary technology to deliver a specially-formulated amikacin (NKTR-061), an aminoglycoside antibiotic, for inhalation deep into the lung.

Under the deal, Nektar will receive milestone payments of up to $175 million associated with the successful development and commercialisation of NKTR-061. This includes an upfront payment of $50 million.

Following clinical and regulatory development, Bayer HealthCare and Nektar will co-promote the product in the U.S. and share profits.

For sales outside the U.S., Nektar will receive tiered performance royalties up to a maximum of 30%.

Bayer HealthCare in a statement on Monday said it will be responsible for the global clinical development, regulatory strategy, manufacturing and marketing of the product, with Nektar participating in all aspects of decision making and governance.

"This development agreement reinforces our commitment to fight infectious and respiratory diseases and is a natural fit with Bayer HealthCare's strategy of developing and marketing specialty pharmaceutical products," Ulrich Köstlin, board member of Bayer Schering Pharma, said.

NKTR-061 is currently being studied in Phase II trials for the adjunctive therapy of ventilated patients with hospital-acquired, Gram-negative pneumonias.

Bayer HealthCare and Nektar started working together in 2005 with the joint development of inhaled ciprofloxacin as a potential dry powder therapy for treating pseudomonal infections in patients suffering from cystic fibrosis.

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vincent.landon@apmnews.com
[7741] 07/08/2007 07:10 GMT - RESPIR

LONDON, Aug 7 (APM) - Health Canada has granted its second marketing approval of GW Pharmaceuticals' cannabis-based Sativex, as an adjunctive analgesic treatment in adults with advanced cancer who experience moderate to severe pain, it was announced on Tuesday.

The joint statement from GW Pharma and Bayer said the Canadian approval is for cancer patients who continue to experience moderate to severe pain despite receiving the highest tolerated dose of strong opioid therapy for persistent background pain.

Sativex, which is marketed in Canada by Bayer HealthCare Pharmaceuticals, is not approved anywhere else in the world.

This is the second approval of Sativex by Health Canada. In 2005, it granted marketing authorisation of the orally administered spray as an adjunctive treatment for the symptomatic relief of neuropathic pain in multiple sclerosis, under its NOC/c policy.

The statement said the latest approval comes with conditions also "under the Notice of Compliance with Conditions (NOC/c) policy".

Bayer and GW added: "This authorisation reflects the promising nature of the clinical evidence which will be confirmed with further studies."

Products approved under Health Canada's NOC/c policy have demonstrated promising benefit, are of high quality and possess an acceptable safety profile based on a benefit/risk assessment for the approved use, the statement added.

Dr Lawrence Librach, director of the Temmy Latner Centre for palliative care at Mount Sinai Hospital and vice president of the Canadian Hospice Palliative Care Association said: "Cancer pain is not managed as well as it could be and the resources available to manage cancer pain effectively are still somewhat limited. Cannabinoids have an important role in treating complex cancer pain particularly neuropathic pain and demonstrate a positive effect with current treatment options."

The companies said the efficacy of Sativex has been demonstrated in a double-blind placebo controlled parallel group study in patients with cancer pain.

Patients in the study had advanced cancer and were experiencing pain that was not responding adequately to strong opioid medication, such as morphine. In addition to study medication, all patients remained on their existing opioid and other analgesic medication during the trial.

In this study, Sativex achieved a statistically significant improvement in pain relief, in comparison with placebo.

The study further showed that in patients with advanced cancer who were already taking the strongest available pain treatments, more than four of 10 patients taking Sativex were able to achieve a further clinically important reduction in pain.

According to the Canadian Cancer Society, an estimated 159,900 new cases of cancer and 72,700 deaths will occur in Canada this year alone. On average, each week 3,075 Canadians will be diagnosed and 1,398 will die of cancer.

EUROPEAN DISAPPOINTMENT

Last month GW Pharmaceuticals withdrew its European filing for Sativex in the treatment of MS spasticity following demands for additional data from Britain's MHRA, although it said it expected to file again next year.

It filed an application for Sativex in 2006 under the decentralised procedure in four European countries (UK, Spain, Denmark, Netherlands).

While Sativex has not yet been approved by any medical authorities outside Canada, GW has licensed Sativex to Bayer Healthcare for the UK market and to Almirall Prodesfarma for the remainder of Europe.

GW on its website said it took the first major step towards the U.S. market in January 2006 when it announced that the Food and Drug Administration (FDA) had accepted the company's Investigational New Drug (IND) Application for Sativex.

The approved IND application was for a Phase III trial to investigate the use of Sativex in the treatment of pain in patients with advanced cancer that has not been adequately relieved by opioid medications, which GW plans to start this year.

nh/ak

nick.hudson@apmnews.com
[7742] 07/08/2007 08:07 GMT - CANCER NEURO

BERLIN, Aug 7 (APM) - Second-quarter sales at Bayer HealthCare rose 65% to 3.72 billion euros, Bayer announced on Tuesday.

Pharmaceuticals' sales rose 1.395 billion euros to 2.583 billion euros, with Schering accounting for 1.489 billion euros.

The pro rata figure for the same period of 2006 was 144 million euros with Schering's results included in Bayer Group's statements from June 23, 2006.

"We remain confident about the development of our business in the second half," Bayer CEO Werner Wenning said in a statement.

He expressed particular optimism about its healthcare business. "We continue to expect that all of its divisions will grow with or faster than the market," he said.

Bayer is targeting an underlying EBITDA margin (earnings before interest tax depreciation and amortisation) of 25% for its healthcare business for 2007 and aiming to raise this to about 28% by 2009.

The merger of Schering is proceeding more quickly than planned, with cost savings of more than 800 million euros expected to be achieved by 2009, the company said.

Sales of the haematology/cardiology business rose 19 million to 271 million euros, representing an increase of 18% after adjustments principally for exchange rate effects.

Its oncology business boosted sales by 75% to 188 million euros, on a currency adjusted basis. Included in this figure is 113 million euros sales of Schering's oncology division. Sales of new cancer medicine Nexavar, leapt 161% to 60 million euros.

The dermatology business achieved sales of 66 million euros in the second quarter.

Sales of the consumer health division rose 6% (9.6% increase on a currency adjusted basis) to 1.134 billion euros.

The consumer care division posted second-quarter sales of 624 million euros, representing a 3% gain. Adjusted for currency effects, sales rose 6%.

The diabetes care business showed a gain of 15% (19.7% currency adjusted) to 244 million euros.

In the second quarter, Bayer group sales grew by 22% to 8.217 billion. Adjusted for currency and portfolio effects, sales rose by 5.4%. Net income improved by 46% to 660 million euros.

Wenning said Bayer continued to target an increase of more than 10% in group sales for the full year 2007. Adjusted for portfolio and currency effects, business should expand by about 5%.

In June, Bayer had already raised its full-year earnings guidance for 2007 and 2009, with the underlying EBITDA margin for the group expected to increase to more than 20% for the current year and over 22% in 2009.

Key products in the second quarter in millions of euros:

:: Betaferon/Betaseron (Schering), 256 million +3% (pro forma)

:: Yasmin/YAZ/Yasminelle (Schering), 250 million +38% (pro forma)

:: Kogenate 210 million +17%

:: Adalat, 162 million (-5.3%)

:: Ascensia, 107 million (-7%)

:: Aspirin, 107 million (-7%)

:: Cipro/Ciprobay, 93 million (-26%)

:: Avalox/Avelox, 90 million +2%

:: Mirena (Schering) 88 million +17% (pro forma)

:: Levitra, 81 million +11%

:: Glucobay, 79 million +4%

:: Nexavar, 60 million +161%

:: Canesten, 47 million +18%

:: Diane (Schering), 43 million (-4%) (pro forma)

:: Bepanthen/Bepanthol, 40 million +18%

vl/nh

Vincent.landon@apmnews.com
[7743] 07/08/2007 08:52 GMT - INDUSTRY

LONDON, Aug 7 (APM) - Pfizer is planning to launch its new HIV drug maraviroc in the U.S. in the middle of September after gaining accelerated approval there, the company said late on Monday.

The drug was recommended to the U.S. Food and Drug Administration by an advisory panel of experts in April and the agency sent Pfizer an approvable letter in June.

It has gained accelerated FDA approval for the combination treatment of adults infected with only CCR5-tropic HIV-1 detectable disease, who have evidence or viral replication and have HIV-1 strains resistant to multiple antiretroviral agents.

The FDA said in a statement that 50-60% of HIV-infected patients have circulating CCR5-tropic HIV-1.

The product's label will include a boxed warning about liver toxicity and a statement in the warnings/precautions section about the possibility of heart attacks.

It will be known as Selzentry in the U.S. and as Celsentri elsewhere.

The product gained a CHMP positive opinion on its European approval in July and Pfizer said it was currently filing applications elsewhere in the world.

Industry analysts have projected the product could sell about $500 million by 2011 once it reaches the market.

Pfizer said the drug - which blocks viral entry into white blood cells - is the first in a new class of oral HIV medicines for more than 10 years.

ak/nh

ailis.kane@apmnews.com
[7744] 07/08/2007 09:02 GMT - AIDS

LONDON, Aug 7 (APM) - Analysts in London on Tuesday expressed their optimism for the UK's GW Pharmaceuticals after its cannabis-based Sativex drug received its second approval in Canada.

Ibraheem Mahmood of Investec Securities said in a research note that the latest conditional approval for cancer pain reinforces his buy recommendation.

He is urging investors to buy the stock at 70 pence a share (1.02 euros) and has set a target price of 2 pounds 37 pence (3.48 euros). GW's shares rose 4% to 72.75 pence on the London stock market shortly after the second approval was announced in morning trade on Tuesday.

"Today, this cannabis-based product has been given the green light in Canada for managing the often desperate symptoms of intractable pain in cancer," Mahmood said.

"In our view, this proves what many doctors believe, that Sativex works and has broad application. So, that while today's announcement is in our target price, it is far from the share price. Jaded markets may stunt market response, however, we reiterate our buy."

Mahmood said the market is "punch-drunk" from near-miss Phase III trials/approvals. While he predicted a 5% gain or more in the share price today, he believes the shares will come in for short-term profit taking in the coming days.

"The market will only 'believe' a full approval in a major market. The earliest chance for this is following a successful Phase III trial in neuropathic pain early next year."

NEUROPATHIC PAIN

Dr Gary Waanders of broker Nomura Code Securities told APM he believes GW will resubmit Sativex for approval in Europe for neuropathic pain in multiple sclerosis in the first half of 2008, with approval likely the following year.

Last month, GW withdrew its European filing for Sativex in the treatment of MS spasticity following demands for additional data from Britain's MHRA.

Dr Stephen Wright, GW's R&D director, said then: "We expect to re-submit our application to the regulators in Europe in 2008, either in the indication of MS Neuropathic Pain or MS Spasticity."

But Waanders believes the company will file in the MS neuropathic indication first as the MS spasticity was too complicated, requiring additional data.

He added that the company has suffered at the hands of regulators previously and fears about its psychotic effects as often mentioned when used as a recreational drug, will disappear.

"Sativex is intended to be used as a last resort as a cancer pain control. Sales are likely to start slowly but will pick up as people become more familiar with it. Sativex has a better side-effect profile than better-known opiods. On balance I like this company."

nh/ns

nick.hudson@apmnews.com
[7745] 07/08/2007 11:07 GMT - CANCER NEURO

By Ailis Kane

LONDON, Aug 7 (APM) - Pfizer says it is on track towards tripling its late-stage pipeline by 2009, despite the loss of 13 products since its last pipeline update.

Pfizer said has total of 99 development programmes, including 47 products in Phase II, 11 in Phase III and three in registration, it said in a late Monday statement.

The company has dropped 13 drugs since first posting its pipeline on its website in December.

According to Associated Press these included eight early-stage drugs for obesity, atherosclerosis, diabetes and cancer, four mid-stage products for atherosclerosis, obesity, dermatology and lung cancer and one previously announced lung cancer product in late stage testing.

Analyst Jacob Plieth from Edison Investment Research said told APM that Pfizer, "didn't give much away" in the pipeline update. It was unclear whether the drugs had failed for safety or efficacy reasons, or whether they simply did not fit with Pfizer's commercial priorities, he said.

In the statement, Pfizer's chairman and CEO Jeff Kindler said the firm had made efforts to reduce its attrition rates and enhance its clinical productivity.

But Plieth said this did not apparently include any sign of following its competitors such as GlaxoSmithKline, Novartis, Roche and AstraZeneca in holding new biotech acquisitions at arms' length as semi-autonomous subsidiaries. "Incorporating biotech companies into a large corporate structure has failed in the past."

Mike Ward from Nomura Code told APM the Pfizer pipeline was not the biggest in the industry, with GlaxoSmithKline having more new chemical entities with Roche "not far off" GSK's total.

Ward said Pfizer was under some pressure to rehabilitate its pipeline in the face of patent expiries, some of them sooner than expected. The company lost a predicted key growth driver, the HDL-raiser torcetrapib, in December when it stopped late-stage trials due to safety concerns.

He said the company showed it had a broad based pipeline, and 47 products in Phase II was a 'nice' number.

But other analysts are less convinced.

Joseph Tooley from A G Edwards & Sons told Associated Press in an interview: "The announcement shows that breadth of their pipeline, and they do have a lot going on in their early phase pipeline. But it's difficult to see which early stage compounds have blockbuster potential."

CANCER A KEY FOCUS

Pfizer's John LaMattina, president of Pfizer global R&D, who is retiring this year, said: "We are revising the allocation of our capital so that we target the areas of greatest medical and commercial promise, and I am confident that you will see Pfizer bring forward significant new therapies to fight cancer, cardiovascular disease, neurological disorders, infections and many other conditions."

The pipeline update showed cancer as a "major focus" for Pfizer, said the statement, with the firm investing more than 20% of its development budget in the area.

Highlights of the cancer portfolio included Sutent (sunitinib), which is "progressing well" in Phase III in non-small cell lung and breast cancers and has just entered Phase III in colorectal cancer.

The multi-targeted anticancer was launched late last year for renal cell carcinoma and gastrointestinal stromal tumours.

Another Phase III anticancer is axitinib, which entered a pancreatic cancer study in July. New data suggested that axitinib plus standard chemotherapy could prolong overall survival, Pfizer said.

In metastatic melanoma, its Phase II immunotherapy CP-751871 has shown a positive survival trend and it also has CP-675206 is in a Phase III trial in the indication.

Pfizer said it continued to build on its "traditional strengths" in cardiovascular research.

It is bullish on the prospects for its anticoagulant apixaban, which it licensed from Bristol-Myers Squibb earlier in the year, with its plans for a head to head superiority trial against Sanofi-Aventis's Lovenox (enoxaparin).

The Phase III study will compare the drugs' efficacy in venous thromboembolism in patients undergoing total knee replacement surgery. Apixaban is also in Phase II for acute coronary syndrome.

Pfizer has revived its hopes for selective oestrogen receptor modulator lasofoxifene for osteoporosis, which it plans to resubmit in the U.S. in December with new data.

Pfizer previously received a non-approvable letter for the drug in 2005. It did not say what the new data added to the previous failed filing.

Other metabolic compounds include CP-945598 for obesity (Phase III) and CP-533536 for bone healing (Phase II).

Building on from its existing pain franchise, Pfizer has eight candidates for the treatment of pain, including a selective noradrenalin reuptake inhibitor S,S-reboxetine (Phase II in fibromyalgia), and PF-4383119 (Phase IIa) and PF-592379 (Phase II) both for osteoporosis pain.

In its central nervous system portfolio, Pfizer is working on line extensions for Geodon (ziprasidone) and Lyrica (pregabalin) as well as alpha-2-delta compounds for neurological disorders and PD-332334 for generalised anxiety disorder.

In its anti-infectives programme, it is combining two of its launched antifungals Eraxis (anidulafungin) and Vfend (voriconazole) at Phase II.

ak/ns

ailis.kane@apmnews.com
[7746] 07/08/2007 11:12 GMT - INDUSTRY

BERLIN, Aug 7 (APM) - German statutory health insurers saved 2.41 billion euros on drug spending in the first six months of the year by using generic drugs, said Pro Generika the generic manufacturers' association on Tuesday.

The latest market figures show that the average pharmacy retail price for generics sold was 19.47 euros between January and June, Pro Generika said.

It added that the median price for off-patent branded medicines was 32.66 euros, making generics on average 13.19 euros cheaper.

Pro Generika said doctors prescribed cheaper generics in 183 million cases in the first half of the year.

Extrapolating from half-year savings of 2.41 billion euros gave full-year savings of about 4.8 billion euros, some 1.4 billion euros more than in 2005, Pro Generika said.

COMPETITION UNPRECEDENTED

It added that the additional cost savings were not only due to increased prescribing of generics but also because of unprecedented competition in the generics sector.

Between March 2006 and April 2007, manufacturers cut prices for generics by 835 million euros, it said.

Discount deals between health insurers and generic manufacturers also produced savings.

Pro Generika said there was still room for more savings because doctors prescribed off-patent branded medicines when cheaper generics existed in 41 million cases. Health insurers could save a further 541 million euros if these physicians also switched to generics.

The German Association of Pharmacists (ABDA) said last month that drug spending by the statutory health insurers rose 5.7% to nearly 12.4 billion euros in the first half of 2007.

Pro Generika said the rise was partly due to January's 3% hike in value added tax (VAT) as well as the rising cost of patented drugs.

vl/ak

vincent.landon@apmnews.com
[7747] 07/08/2007 11:20 GMT - INDUSTRY

PARIS, Aug 7 (APM) - Sweden's Capio announced on Tuesday it has bought a majority stake in Swiss diagnostics group Unilabs and will make a cash offer for the remaining shares.

Capio is primarily known for its clinics, but it also has a diagnostics division in Sweden, Norway, Denmark, Finland and the UK.

The latest annual data published by Capio, in 2005, put diagnostics' sales at 1.321 billion Swedish kronor (143 million euros), 12% of the group's total sales.

Capio has spent 282 million Swiss francs (173 million euros) on 50.08% of voting rights and 38.1% of the capital of Unilabs, a company founded in 1987 which specialises in laboratory equipment.

The Swedish group will now make a public offer for the remaining shares, of 28.75 Swiss francs per registered share and 57.50 Swiss francs per bearer share. This values the company at about 575 million Swiss francs (351 million euros).

Unilabs' registered shares closed at 47.70 Swiss francs on Monday, so Capio's offer represents a 20.5% bonus - 27% over the last 30 days of trading and 30% over the last 60 days, Capio says.

The transaction received unanimous support from Unilabs' board and is expected to be completed by the end of the year.

Capio intends to merge its diagnostics activity with Unilabs. The new business, with 2,800 employees, will keep the Swiss group's name and will be based in Geneva. It is likely to have annual sales of more than 510 million Swiss francs (311 million euros).

"The combination with Capio Diagnostics enables Unilabs to expand its current footprint to Scandinavia and to the UK. In addition, it provides access to capital to fund further European expansion and to profit from upcoming consolidation opportunities," said Unilabs founder and executive chairman Edgard Zwirn.

"The companies are a perfect fit with over 100 laboratories and testing facilities across Europe," added Capio CEO Paul Hokfelt.

eh/cb/clg/nh

edouard.hubert@apmnews.com
[7748] 07/08/2007 11:26 GMT - INDUSTRY

LONDON, August 7 (APM) - TopoTarget said on Tuesday following kidney safety fears it would stop enrollment for the Phase II study of belinostat (PXD101) in combination with Velcade (bortezomib) for multiple myeloma (MM).

Although two of the four patients enrolled with advanced refractory MM developed acute deterioration in already existing renal insufficiency (ARI), the company was confident this would not affect the development of belinostat in other indications.

The remaining 14 Phase I and II studies with the HDAC inhibitor for various cancer indications would continue, it said.

TopoTarget's share price appeared unaffected by the news in morning trading on the Copenhagen Stock Exchange.

Peter Buhl Jensen, TopoTarget CEO said in a statement: "Our data show that this finding is limited to patients with multiple myeloma, a population known to be at risk of this complication due to pre-existing renal changes.

"Until we know more about how to prevent the complication in this specific patient population, we have decided not to enrol further patients in this trial and will focus our resources onto the other ongoing studies in cancer indication where belinostat is demonstrating a therapeutic benefit."

ARI has not been evident in any of the other 14 belinostat studies, although "three similar events were seen in previously conducted single agent studies with belinostat in patients with MM."

A second study with belinostat in combination with velcade sponsored by the National Cancer Institute, U.S. (NCI) against solid tumours and lymphoma, was unaffected by ARI.

OVARIAN TRIAL EXPANDED

TopoTarget also announced progress in three other indications where belinostat is being tested.

The Phase II trial with belinostat in combination with carboplatin and paclitaxel against ovarian cancer, has produced three partial responses, of which one is unconfirmed, in 23 pre-treated patients suffering from recurrent ovarian cancer. 14 patients remain in the study.

TopoTarget said the response had triggered an expansion of enrolment to include 32 patients.

The same combination of belinostat with carboplatin and paclitaxel is also being studied in bladder cancer, where 15 patients are expected to be enrolled in a safety and efficacy Phase II study.

Finally TopoTarget said a Phase I/II trial with belinostat in combination with idarubicin against acute myelogenous leukaemia is being initiated in Europe. The company said it aimed to enrol 70 patients to determine the maximum tolerated dose.

Further results on the belinostat trials are expected in the fourth quarter of 2007.

The studies are performed by TopoTarget, CuraGen and the NCI.

In 2006, TopoTarget saw a net loss of 174.4 million kroner (23.4 million euros) - an increase of over 280% on 2005 following the launch of Savene (topoisomerase II inhibitor) for chemotherapy-related extravasation.

The Danish biotech also reported a 40% fall in revenues to 45.7 million kroner (6.1 million euros) for 2006.

Second quarter results from TopoTarget are expected on August 15.

kl/ns

kari.larsen@apmnews.com
[7749] 07/08/2007 11:46 GMT - CANCER

LONDON, Aug 7 (APM) - NICE on Tuesday issued new draft guidance on stents, approving the much more expensive drug-eluting variety for use only in a subset of patients.

Stents should be used routinely in percutaneous coronary intervention (PCI) in patients with either stable or unstable angina or with acute myocardial infarction (MI), NICE said in its initial assessment of the devices.

However, the decision whether to use a bare-metal stent (BMS) or drug eluting stent (DES) should be made on the "anatomy of the target vessel ... and the symptoms of mode and presentation of the disease", NICE said.

NICE included examination of Johnson & Johnson's sirolimus-eluting stent, Cypher and Boston Scientific's paclitaxel-eluting stent, Taxus, in its assessment before giving precise guidance on when they should be used.

Cypher or Taxus were recommended in PCI for patients with symptomatic coronary artery disease (CAD), in whom the target artery is less than 3 mm in internal diameter or the lesion is longer than 15 mm.

However, this guidance did not apply when the patient had experienced a MI in the preceding 24 hours, or for whom there is angiographic evidence of thrombus in the target artery.

If more than one artery required stenting, each artery should be considered separately using the advice above.

DRUG ELUTING TOO EXPENSIVE

NICE said its early advice was based on the much higher price the UK's National Health Service had to pay for drug eluting stents, compared to the bare metal variety.

It said prices for BMS range from about 600 pounds to 900 pounds (880-1,320 euros) and for DES from about 1,300 pounds to 1,500 (1,900-2,200) per stent.

For bare-metal and drug-eluting stents that are the same apart from their drug-eluting properties, the difference in cost is about 500 to 600 pounds (735-882 euros), NICE observed.

Elsewhere NICE noted that approximately 39,000 PCI procedures were undertaken in the UK in 2001, equating to 663 per million of the population - a rate that had increased at an average of 14% per year over the previous 10 years.

However, the rate for the UK remains below that of the European Union average, which exceeded 1,000 per million of the population.

NICE's document is now open for consultation with comments accepted until August 28 followed by a second Appraisal Committee meeting on September 4.

ns/nh

nick.smith@apmnews.com
[7750] 07/08/2007 13:51 GMT - CARDIO