Uh oh

ALLSCHWIL/BASEL, SWITZERLAND - 17 November 2010 - Actelion Ltd (SIX: ATLN) announced today that - as part of its ordinary course of business - the company is in regular dialogue with other industry participants. No further comment will be made.


Translation: we are selling....

 

Re: Uh oh / Liver damage

Dec. 17 (Bloomberg) -- Swiss stocks declined as an agreement by European Union leaders to create a permanent debt- crisis mechanism failed to assuage concern that contagion will spread to other indebted countries in the region.

Actelion Ltd. decreased 2 percent after Europe’s medicines regulator started a review that includes the Swiss company’s Tracleer drug. Roche Holding AG lost 1.1 percent as health-care companies retreated across Europe.

The Swiss Market Index of the biggest and most actively traded companies dropped 0.4 percent to 6,538.16 at the 5:30 p.m. close in Zurich, paring the weekly gain to 0.3 percent. The benchmark measure has rallied 10 percent since its low for the year on July 5 as corporate earnings rose and the European Union bailed out Ireland. The broader Swiss Performance Index lost 0.3 percent today.

EU leaders agreed to amend the bloc’s treaties to create a permanent crisis-management mechanism in 2013, while divisions flared over the steps to prevent Portugal and Spain from needing future bailouts.

Germany, the biggest contributor to Europe’s bailouts of Greece and Ireland, pushed through an accord to set up a system that will allow financial aid “if indispensable” to underpin the euro. The accord may force bondholders to bear some of the costs of future rescues.

Ireland’s credit rating was cut five levels by Moody’s Investors Service and further downgrades are possible as the government struggles to contain losses in the country’s banking system. Moody’s also placed Greece’s Ba1 bond ratings on review for a possible downgrade, citing heightened concerns about whether the country will be able to reduce its debt to “sustainable levels”.

German Confidence

In Germany, business confidence unexpectedly rose to a record in December as stronger domestic demand helped bolster the recovery in Europe’s largest economy.

The Munich-based Ifo institute said its business climate index, based on a survey of 7,000 executives, increased to 109.9 from 109.3 in November. That’s the highest since records for a reunified Germany began in 1991. Economists predicted a drop to 109, the median of 36 forecasts in a Bloomberg News survey.

In the U.S., the index of leading economic indicators increased in November by the most in eight months, signaling that the pace of the economic recovery will quicken early next year.

The Conference Board’s gauge of the outlook for the next three to six months rose 1.1 percent after a revised 0.4 percent gain in October, the New York-based group said today. The reading matched the median forecast of economists surveyed by Bloomberg News.

Liver Damage

Actelion dropped 2 percent to 50.70 Swiss francs after the European drug regulator started reviewing a class of medicines that includes Tracleer. The European Medicines Agency began its review after Pfizer Inc. pulled one of its treatments from the market because it was linked to potentially life-threatening liver damage.

The EMA will examine the class of drugs used to treat pulmonary arterial hypertension, a potentially fatal condition that causes high blood pressure in the artery moving blood from the heart to the lungs. Pfizer’s Thelin may have led to two cases of fatal liver injury, the agency said today.

 

The EMA will examine the class of drugs used to treat pulmonary arterial hypertension, a potentially fatal condition that causes high blood pressure in the artery moving blood from the heart to the lungs. Pfizer’s Thelin may have led to two cases of fatal liver injury, the agency said today.

How many cases of fatal liver injury has Tracleer caused that was not reported in a timely manner or in the way that the FDA mandated?

 

EMA Reviewing Drug Class That Includes Pfizer’s Thelin
December 16, 2010, 1:02 PM EST
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e-mail this story print this story 0diggsdiggadd to Business Exchange By Kristen Hallam

(Adds agency comment in second paragraph.)

Dec. 16 (Bloomberg) -- Europe’s drug regulator is reviewing a class of medicines that includes Actelion Ltd.’s Tracleer and Gilead Sciences Inc.’s Letairis after Pfizer Inc. pulled a treatment from the market because it was linked to potentially life-threatening liver damage.

The drugs are used to treat pulmonary arterial hypertension, a potentially fatal condition that causes high blood pressure in the artery moving blood from the heart to the lungs. Pfizer’s Thelin may have led to two cases of fatal liver injury, the European Medicines Agency said in an e-mailed statement today.

Thelin, Tracleer and Letairis, which is sold outside the U.S. as Volibris, are known as endothelin receptor antagonists. The drugs’ toxicity to the liver may vary in intensity and frequency, the agency said. GlaxoSmithKline Plc markets Volibris outside the U.S.

The agency’s Committee for Medicinal Products for Human Use will begin to review whether the drugs “remain a valuable option in the treatment of pulmonary hypertension,” according to the statement. Strict recommendations about dosing and monitoring have to be followed, the agency said.

Roland Haefeli, a spokesman for Actelion in Allschwil, Switzerland, declined to comment. A spokesman for Foster City, California-based Gilead referred questions to London-based Glaxo. Glaxo didn’t immediately respond to a voice message left at the press office.

Pfizer’s Statement

No new patients should be prescribed Thelin and those receiving it should be transferred to other therapies, Pfizer, based in New York, said in a Dec. 10 statement. The company halted trials of the medicine.

Thelin was sold in the EU, Canada and Australia. It’s not approved in the U.S. The drug generated $44.4 million in the first three quarters of 2010, said Pfizer spokesman Curtis Allen.

Pulmonary hypertension is an incurable condition where there is increased pressure in the arteries of the lungs, causing shortness of breath, according to the National Institutes of Health.

Actelion got about 85 percent of its revenue last year from Tracleer, which has dominated the market for pulmonary arterial hypertension since it won approval in 2001. The drug generated 1.51 billion Swiss francs ($1.56 billion) in sales in 2009.

Other treatments for pulmonary hypertension include oxygen, Pfizer’s Revatio, calcium channel blockers, which relax the muscles in the wall of the blood vessels, and diuretics, which lower the amount of water in the body, reducing the amount of work the heart has to do, according to the Mayo Clinic.

--Editors: Phil Serafino


Actelion spokseman has no comment, why not stand behind the safety of your drug based on an accurate track record and and accurate reporting of side effects? Maybe the reporting is not accurate for a reason?

Also, this may be a blow to Gilead's efforts in the US of getting liver monitoring reduced or lifted for ambrisentan .

 

UPDATE 1-Actelion says 2010 EBIT to be under guided range


* 2010 EBIT growth slightly below 21-24 percent guidance

* Says higher legal costs key factor in 2010 lower EBIT

* Reiterates 2011 financial outlook


ZURICH, Jan 10 (Reuters) - Actelion Ltd (ATLN.VX), Europe's largest biotech company that has been subject to repeated takeover speculation, warned that full-year earnings before interest and tax (EBIT) would miss its guided range.

Actelion Chief Executive Jean-Paul Clozel was due to tell a J.P. Morgan healthcare conference that Actelion would meet its target for growth of 2010 net revenue in the low double digit range in local currencies, the firm said in a statement.

But it said EBIT growth would "slightly" miss Actelion's guided range of 21-24 percent due to higher than expected legal costs, without elaborating.

Actelion said Clozel would reiterate the 2011 financial outlook, with sales in local currencies expected to increase in the mid-single digit range.

"Even though 2011 is likely to be a more challenging year financially, as a result of the continued pricing pressure which the entire pharmaceutical industry is facing, Actelion remains one of the best positioned biotechnology companies globally," he said.

Actelion shares have soared in recent months due to takeover speculation, particularly surrounding Amgen (AMGN.O), with analysts speculating the U.S. company and world's largest biotech could pay $9.8 billion, or $75 per share. (Reporting by Emma Thomasson; Editing by David Cowell)


"2011 with sales in local currencies expected to increase in the mid-single digit range." So after you factor in the annual price increases (which is almost a given), you are expecting actually to lose business.

 

"higher than expected legal costs"

Hmmm...

 

2011-02-11 BioPharm Insight Actelion's (VTX:ATLN) macitentan is expected to face a high bar in generating convincing safety and efficacy data in its Phase III morbidity and mortality trial in pulmonary arterial hypertension (PAH), experts said. Performance exceeding current marketed competitors from the same drug class remains doubtful, they added. Macitentan is a highly potent tissue-targeting endothelin receptor antagonist, and through complete tissue blockade of tissular endothelin, macitentan is expected to protect tissue from the damaging effect of elevated endothelin specifically in the cardiovascular system, according to Actelion's website. The SERAPHIN Phase III study is being conducted to evaluate safety and efficacy through the primary endpoint of morbidity and all-cause mortality in patients with symptomatic PAH, according to the company's website. Actelion declined to comment for this article. Actelion's Tracleer (bosentan) and Gilead's (NASDAQ:GILD) Letairis (ambrisentan) are the current marketed drugs used to treat PAH and are also endothelin receptor agonists, said Dr Robert Vender at Penn State Hershey Pulmonary Medicine. These marketed drugs had a primary endpoint of the 'six minute walk test' as opposed to morbidity and mortality (prevention of disease progression) and don't have a mortality label. If macitentan can hit this endpoint and get the mortality label, then it will "jump to the head of the class", but this may be tough to achieve, experts noted. The FDA is "frustrated" with the six-minute walk test endpoint for PAH studies as being sufficient for efficacy, said Dr Steven Nathan, medical director of the advanced lung disease program at Inova Fairfax Hospital in Falls Church, Virginia. The best endpoint is mortality but these studies are hard to do in an ethical context, he noted. With PAH, it is important to look for the long-term effect with the trial design so the morbidity/mortality endpoint is valid and preclinical data looks favourable, said Dr Richard Channick, director of the pulmonary hypertension program at Massachusetts General Hospital, and a consultant for Actelion. Tracleer and Letairis were never studied for the mortality endpoint; if they were, it is quite possible that they might also show the same benefit, Nathan said. Macitentan will also likely have the same toxicity as its competitors, as it is a "class effect," said Vender. Tracleer was first to market and has well established efficacy, but is associated with liver toxicity and teratogenicity, requiring regular pregnancy testing, and these are the key downfalls with this treatment with its "laborious" monitoring process, he said. Macitentan might have a differing degree of toxicity (as Letairis appears to have less toxicity than Tracleer, according to the company's ongoing study and data); however, teratogenicity is going to be there "no matter what" with this class of compounds. In addition, Pfizer (NYSEFE) voluntarily withdrew Thelin (sitaxentan - approved in the EU, Canada and Australia) of the same class from the market in December due to emerging liver safety concerns. Following this withdrawal - along with the FDA's "safety first" stance and the well known adverse reaction profile of endothelin antagonists - safety data from the Phase III and any efficacy differences in EU and ex-EU sites will be important in determining macitentan's future, said Dr Krishan Maggon, new drug development and licensing expert and consultant. The risk of liver enzyme elevations is significant but is less than 10%, said Dr Marco Confalonieri, director of pneumology at the University Hospital of Trieste, Italy. He additionally noted that the ongoing trial should also look for gastrointestinal adverse events. An investigator on the trial had so far not seen any safety concerns in the ongoing trial and said dosing has not been a major issue in the study. Vender highlighted that 40-50% of patients are on Tracleer, which has been well established in the treatment setting for so many years. Bosentan has 10-15 years of data and Letairis has around five years. PAH is not a big population indication that would generate "quick data", and for a third-to-market drug like macitentan, it is going to be very difficult to convince physicians to use it, he said. Additionally, without a direct comparison, Actelion will not be able to convince physicians that the drug has a benefit beyond Tracleer and Letairis when they go generic in 2015, said Dr Mark Klapholz, an associate professor of medicine and director of cardiology at the New Jersey Medical School and an investigator on the study. However, the drug does have the potential to show improved tissue penetration, said Confalonieri. Klapholz agreed that macitentan may have better tissue penetration than Letairis and Tracleer but this difference may not be clinically relevant because tissue angiotensin converting enzyme inhibition (ACEI) was not better than non-tissue ACEI. Channick noted that improved tissue penetration potential may translate into fewer side effects like liver abnormalities and edema, which would additionally translate into a better efficacy profile. Enrollment in the trial completed in December 2009 with a total of 742 patients, and, according to Clinicaltrials.gov, the study is expected to be completed in March 2012. Actelion has a market cap of CHF 7bn (EUR 5.3bn). by Surani Fernando in London and Sasha Coffiner in New York

Great information about the issues macitentan will face. This could be a huge problem.

 

I hear they are calling reps now, even former ones. Yikes!

 

This is true.

 

I never answer my home phone or check for VM. My cell is in a company name, not a Pharma co, my family company. I hope they don't come to the house looking for us. It does happen.

 

It's no secret that some DMs encouraged off label use. The DOJ would be smart to investigate the DMs, not the reps who are treated like serfs (unless you're a favorite good ol'boy).

 

Why not subpoena most of the current and former MSLs? They were nothing but off-label sales reps despite what management said.

 

yea, they will never find you! The Feds only use phone records. Could you really be that big of a dumbass?

 

I am well aware of the FDA/FBI process as they have contacted me at my home 10 years ago, about 7am is the MO. Get a grip and a sense of humor. You are the idiot here.

 

What happens with this? What is the recourse? This is so blantanly wrong. The doctors are refusing to admit what is spelled out everywhere which is this drug is dangerous and DOES kill. As a business if you lost a significant portion of your customers due to your negligent behavior you go out of business but it seems like there are no standards held. To even be able to fight this you have to 'prove' it harmed someone. Well what about proving it didn't? I know this is the business section and all the feedback here is exactly what I suspected was going on from a analytical point of view. But I have another one also- this drug directly killed my child and no one wants to say anything or do anything even though the medical records themselves show what happened. With pictures, records and timelines everyone runs scared. I do understand these companies even when losing money make a enormous amount of money but at what cost?

 

FYI-to my friends at Actelion.

Very unusal 2 hour panel interview taking COPIOUS notes. Weirdest interview I have ever been through. I don't want to come off as paranoid but I don't want to say more.

Please, YOU HAVE BEEN WARNED. Stay on indication, do the right thing. Be careful if you are looking for a job. The storm is brewing and nobody wants to be hit by it.

 

WTF is that supposed to mean? "Panel interview" with who/what?

 

Bayer’s pulmonary hypertension drug riociguat gets US FDA priority review status

Berlin
Tuesday, April 09, 2013, 10:00 Hrs [IST]
The US Food and Drug Administration (FDA) has granted priority review of Bayer HealthCare's New Drug Application (NDA) riociguat (BAY 63-2521) which is an oral agent being investigated as a new approach to treating different types of pulmonary hypertension.

The FDA grants priority review to medicines that offer major advances in care or that provide a treatment where no adequate therapy exists. Under the Prescription Drug User Fee Act (PDUFA), the FDA aims to complete its review within eight months from the submission of the NDA, rather than the standard 12-month review cycle.

At the beginning of February, Bayer HealthCare submitted riociguat, the first drug to demonstrate efficacy in two distinct forms of pulmonary hypertension (inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH)) for regulatory approval in the United States and in the European Union.

“In the pivotal phase III studies, riociguat was shown to be the first drug therapy to demonstrate robust efficacy in two potentially fatal pulmonary hypertension indications,” said Dr Kemal Malik, member of the Bayer HealthCare Executive Committee and Head of Global Development. “To date, no approved pharmacological therapy exists for CTEPH and as a result there is an urgent unmet medical need for patients who are unable to undergo surgery. We hope that we will soon be in a position to provide patients and doctors with a new treatment option.”

The submission is supported by data from the two randomized, double-blind, placebo-controlled pivotal, global phase III studies, namely CHEST-1 and PATENT-1. Results of both studies were presented at the 2012 annual meeting of the American College of Chest Physicians (ACCP) in Atlanta, USA. Both phase III studies with riociguat met their primary endpoint, a change in exercise capacity, after 12- or 16 weeks respectively. Riociguat was generally well tolerated, with a good safety profile.

Bayer HealthCare announced positive data from the interim analysis of the on-going CHEST-2 trial with riociguat, the open-label long-term extension of the pivotal phase III study CHEST-1, at the 5th World Symposium of Pulmonary Hypertension (WSPH) in Nice, France. The results of the CHEST-2 trial support the positive data of the pivotal CHEST-1 trial, showing long-term safety and sustained clinical benefits in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

Riociguat was discovered by Bayer and is the first member of a novel class of compounds, the stimulators of soluble guanylate cyclase (sGC).

Pulmonary hypertension (PH) is a severe, progressive and life-threatening disorder in which the pressure in the pulmonary arteries is significantly increased and which can lead to heart failure and death. Patients with PH develop a markedly decreased exercise tolerance and reduced quality of life. The most common symptoms of PH include shortness of breath, fatigue, dizziness and fainting, all of which are worsened by exertion. As the symptoms of PH are non-specific, diagnosis can be delayed by as much as two years. Early diagnosis is essential as a delay in treatment initiation can have a negative impact on survival. Continuous treatment monitoring is then vital to ensure that patients are receiving optimal care for their particular type and stage of disease.

According to the clinical classification of PH (Dana Point), there are five different types of PH based on underlying causes which are: pulmonary arterial hypertension (PAH), pulmonary hypertension owing to left heart disease (e.g. PH-LVD), pulmonary hypertension owing to lung disease and/or hypoxemia (e.g. PH-COPD or PH-ILD), chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary hypertension with unclear multifactorial mechanisms. Currently available pharmacological treatments are only approved to treat one of the five types of PH, pulmonary arterial hypertension. As a result, there is a strong need for more research to improve understanding of how all five types of PH can be treated effectively.

Bayer Healthcare, a subgroup of Bayer AG is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials.