Replies to post #133380 on Biotech Values

[turtlepower]

AZN (and TRGT) also suffered a setback with tc5214.

http://www.astrazeneca.com/Media/Press-releases/Article/20111220-az-updates-olaparib-TC5214-development

[DewDiligence]

SNY’s Aubagio Fails Superiority to Rebif in Phase-3 Study

[Unlike the prior phase-3 study called TESMO, in which Aubagi easily bested a placebo (#msg-55641299]), the TENERE study reported here had the harder task of beating Rebif, and Aubagio couldn’t do it. This is a big setback for the Aubagio program, IMO. Although SNY has already submitted an NDA (disclosed today) and plans to submit an MAA in 1Q12, the commercial prospects for Aubagio would seem to be bleak.

SNY’s own PR on the TENERE study is at http://finance.yahoo.com/news/Genzyme-Reports-Top-line-bw-2255827539.html?x=0 .]

http://www.bloomberg.com/news/2011-12-20/sanofi-s-experimental-ms-drug-doesn-t-beat-rebif-in-patient-test.html

›By Albertina Torsoli - Dec 20, 2011 5:12 AM ET

Sanofi (SNY), France’s biggest drugmaker, said its experimental pill Aubagio for the treatment of multiple sclerosis failed to beat an older injected therapy at preventing relapses or keeping patients on treatment.

Aubagio, whose chemical name is teriflunomide, showed no statistical superiority to Merck KGaA’s medicine Rebif, Paris- based Sanofi said in an e-mailed statement today. The late-stage trial, dubbed Tenere, showed Aubagio was safe and well tolerated, Sanofi said.

Chief Executive Officer Chris Viehbacher has been building up the company’s multiple sclerosis business since this year’s $20.1 billion purchase of U.S. biotechnology company Genzyme Corp. (GENZ), which gave it access to another experimental MS treatment called Lemtrada. While Aubagio is an oral therapy, Lemtrada is a so-called monoclonal antibody that is injected into patients.

Sanofi is facing competition in the race to introduce MS drugs. Novartis AG (NOVN)’s Gilenya, the first oral drug for the disease, was approved last year and Israel’s Teva Pharmaceutical Industries Ltd. (TEVA) is developing a competing pill, laquinimod. Biogen Idec Inc. (BIIB), the world’s largest maker of medicines to treat MS, said Oct. 26 that its lead experimental medicine, the pill BG-12, was safe and reduced the risk of relapse in a second late-stage trial.

Limited Potential

“Aubagio has the advantage of being an oral treatment, but its potential will be limited by more efficacious drugs,” Eric Le Berrigaud, an analyst at Bryan, Garnier & Co. in Paris, said in e-mailed comments before the trial results were published. “If there weren’t other medicines like Gilenya, BG-12 and even Lemtrada, it would be a great product.”

Le Berrigaud estimates Aubagio may garner 500 million euros ($650 million) in annual sales by 2019, if it is approved.

Multiple sclerosis, which is believed to affect more than 2.1 million people worldwide, is an incurable disease that destroys the nerves and robs patients of their ability to control their movements. Many patients have trouble staying on current therapies because they’re difficult to use or cause side effects, according to the National Multiple Sclerosis Society.

Tenere Trial

The Tenere trial is the second completed study of five planned for Aubagio in MS, Sanofi said. The study, part of the last of three phases of human testing needed for regulatory approval, included 324 patients. The participants were divided into three groups: those who took a 7-milligram dose of Aubagio once a day, those who took 14 milligrams of the drug, and those who took Rebif. The groups were studied for 48 weeks.

Almost half of the patients receiving the lower dose of Aubagio either had a relapse or stopped taking the drug, compared with 37.8 percent at the higher dose and 42.3 percent for Rebif patients, Sanofi said. Annual relapse rates weren’t distinguishable between those taking Rebif and those taking the higher dose of Aubagio, and was higher in the low-dose group, the company said.

Most of the side effects seen in patients taking Aubagio were mild, and included diarrhea, hair thinning and back pain, Sanofi said. Those side effects occurred more frequently in the Aubagio groups than among those taking Rebif, the company said. The most common side effects in the Rebif patients were headache and flu-like symptoms, according to the statement.

A previous Aubagio trial, dubbed TEMSO, showed the drug reduced relapses by 31 percent compared with a placebo [#msg-55641299] and also lowered the risk of disability progression by 30 percent, Sanofi said on Oct. 15, 2010.

Earlier Phases

People suffering from MS probably will use Aubagio in the earlier phases of the disease, while Lemtrada will probably be taken as the disease progresses, Genzyme CEO David Meeker said in a Nov. 14 interview.

“BG-12 and Gilenya will prove tough competitors with respect to oral therapies,” ]no kidding] Peter Verdult and other analysts at Morgan Stanley in London wrote in a Nov. 2 note to clients.

Sanofi’s application for U.S. approval of Aubagio was accepted by the Food and Drug Administration in October, the company said today. The drugmaker said it plans to seek approval in the European Union in the first quarter next year.‹

[DewDiligence]

NVS’ PR on the Raslilez/Tekturna failure in diabetic patients reads as
though NVS is throwing in the towel on this drug for all indications.
The PR is remarkable in disclosing that Raslilez/Tekturna had a negative
profit margin during 2011; it seems highly unlikely that NVS would make
such a revelation if it intended to continue marketing the drug.

http://www.sec.gov/Archives/edgar/data/1114448/000110465911070231/a11-32030_16k.htm

›Novartis announces termination of ALTITUDE study with Rasilez®/ Tekturna® in high-risk patients with diabetes and renal impairment

· ALTITUDE study involved patients with type 2 diabetes and renal impairment who are at high risk of cardiovascular and renal events

· Committee overseeing study identified higher adverse events when Rasilez/Tekturna was added to an ACE or ARB drug in this patient population

Basel, December 20, 2011 — Novartis announced that following the seventh interim review of data from the ALTITUDE study with Rasilez®/Tekturna® (aliskiren), a decision to terminate the trial has been taken on the recommendation of the independent Data Monitoring Committee (DMC) overseeing the trial.

The DMC concluded that patients were unlikely to benefit from treatment added on top of standard anti-hypertensives, and identified higher adverse events in patients receiving Rasilez/Tekturna in addition to standard of care in the trial. Specifically, in the trial arm in which Rasilez/Tekturna was added to the standard of care there was an increased incidence after 18-24 months of non-fatal stroke, renal complications, hyperkalemia and hypotension in this high-risk study population.

The placebo-controlled Phase III ALTITUDE study is the first trial to investigate Rasilez/Tekturna for more than one year in a specific population of patients with type 2 diabetes and renal impairment. These patients are known to be at high risk of cardiovascular and renal events. In the study, Rasilez/Tekturna was given in addition to optimal cardiovascular treatment including an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).

Novartis is in ongoing discussions with health authorities worldwide about the implications of the findings from ALTITUDE for patients. As a precautionary measure Novartis will cease promotion of Rasilez/Tekturna-based products for use in combination with an ACE-inhibitor or ARB.

“Patient safety is the highest priority for Novartis, and we are in a dialogue with health authorities worldwide,” said David Epstein, Division Head of Novartis Pharmaceuticals.

Novartis is recommending that ALTITUDE investigators remove Rasilez/Tekturna-based products from their patients’ treatment regimen and review their high blood pressure medication. Novartis is also reviewing the findings with DMCs of other clinical studies involving Rasilez/Tekturna-based products and combination therapies.

Patients in ALTITUDE should contact their study site for guidance on medication and should not stop treatment until they have seen their physician in view of the importance of controlling high blood pressure. Any patients using Rasilez/Tekturna or other aliskiren combination products who may have questions about their medication should consult their healthcare provider. For more information visit www.novartis.com.

Total sales of Rasilez/Tekturna-based products for the first nine months of 2011 were USD 449 million (1% of Novartis Group sales) and are likely to be negatively impacted by the study results going forward. Product profitability in 2011 was negative. A further update of the actual financial implications will be communicated when the regulatory dialogue has been concluded.

About Aliskiren

Aliskiren was approved in 2007 in the EU and US under the brand-names Rasilez and Tekturna respectively, for the treatment of hypertension (high blood pressure) either as monotherapy or in combination with other medications. The efficacy and safety of Rasilez/Tekturna have been investigated in more than 57,000 patients who have been treated with this medicine in clinical studies.

Rasilez/Tekturna-based products include:

· Rasilez®/Tekturna®

· Rasilez HCT®/Tekturna HCT®, a single-pill combination of Rasilez/Tekturna and hydrochlorothiazide (HCT)

· Valturna®, a single-pill combination of Rasilez/Tekturna and valsartan, available in the US only

· Rasilamlo®/Tekamlo®, a single-pill combination of Rasilez/Tekturna and amlodipine

· Rasitrio®/Amturnide®, a triple combination of Rasilez/Tekturna, amlodipine and hydrochlorothiazide (HCT)

About ALTITUDE

ALTITUDE was a multinational study in 8,606 patients from 36 countries evaluating the potential benefits of Rasilez/Tekturna to reduce the risk of cardiovascular and renal events in this patient population. ALTITUDE was the first randomized, double-blind, placebo-controlled study to investigate Rasilez/Tekturna for more than one year in a specific population of patients with type 2 diabetes and renal impairment. These patients are known to be at high risk of cardiovascular and renal events. In the study, Rasilez/Tekturna was given in addition to optimal cardiovascular treatment including an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB).‹