Trial size may limit use of Seattle Genetics drug (Reuters)

WASHINGTON (Reuters) – U.S. drug reviewers might limit the use of a Seattle Genetics Inc experimental blood cancer drug due to the narrow scope of its clinical trials, sending the company's shares down 3.6 percent.

In documents released on Tuesday the Food and Drug Administration asked an advisory panel to consider the drug, under the proposed trade name Adcetris, for use in previously treated patients with Hodgkin's lymphoma and anaplastic large cell lymphoma (ALCL). About 9,000 Americans a year are diagnosed with Hodgkin's lymphoma and 3,000 with ALCL.

The reviewers suggested the labeling for Hodgkin's should focus on a smaller patient group than expected, limiting potential sales. According to the FDA documents, the drug should be considered for patients who had already been given a stem cell transplant, rather than on all treated patients as suggested by the company.

The FDA advisory panel votes on the drug on Thursday.

Wall Street analysts noted the FDA reviewers had not raised any unusual concerns about the drug's safety or effectiveness.

Cory Kasimov, a JPMorgan analyst, sees an 85 percent chance the drug will be approved for both diseases.

"That said, we still believe that expansion in earlier stages of disease with larger patient markets is critical to the stock's future valuation," he said in a research note.

Howard Liang, an analyst at Leerink Swann, sees U.S. sales at over $400 million for both types of cancer in 2015.

Seattle Genetics shares closed 74 cents down at $19.80 on the Nasdaq. They hit an all-time high of $21.41 on June 28 after European health regulators accepted an application to market the drug for both Hodgkin's and ALCL in Europe.

"The stock is down probably because there are some hints the FDA may not allow as broad a label as the company is seeking," Liang said.

LIMITED DATA FROM TRIALS

In preliminary trials, Adcetris, given in a 30-minute infusion every three weeks, demonstrated complete response rates and reduced tumor size in more than 90 percent of patients -- 94 percent for Hodgkin's and 97 percent for ALCL, the company said.

The FDA said major side effects for both included nerve damage, infections, reactions from the infusion and myelosuppression, a common side effect from chemotherapy that causes decreased blood cell production.

One patient also dropped out of the Hodgkin's study because of Stevens Johnson Syndrome, a life-threatening skin condition.

However, the mid-stage trials only included 58 patients for ALCL and 102 patients for Hodgkin's, and did not compare Adcetris to another drug. The FDA said these factors "limit the benefit-risk analysis."

The FDA reviewers also noted that no second trial confirmed the clinical benefit of Adcetris in patients with ALCL, as required under priority review, and asked the advisory panel to weigh whether the drug should be given an accelerated approval without such confirmation.

Seattle Genetics Chief Executive Clay Siegall told Reuters in May that annual U.S. sales of Adcetris for Hodgkin's and ALCL would likely amount to less than $1 billion.

But if the drug wins approval as a front-line therapy, or first treatment option, the annual U.S. sales could be "considerably over a billion dollars," Siegall said.

He added that he had a "high level of confidence" Adcetris would win U.S. approval by August 30 -- the early decision date set by the FDA. [ID:nN25149337]

The FDA granted priority review status for the drug, known chemically as brentuximab vedotin, meaning the agency believes the medicine is a potentially significant advance over existing therapies.

Brentuximab vedotin links a tumor-targeting antibody to a cancer-killing chemotherapy drug with the goal of limiting side effects. It is designed to home in on an antigen, or foreign substance, in Hodgkin's lymphoma, several types of T-cell lymphoma and other hematologic malignancies.

Seattle holds the full U.S. and Canadian rights to Adcetris, while Japanese drugmaker Takeda Pharmaceutical Co Ltd has the rights for the rest of the world, with milestone payments and royalties going to Seattle.

On June 27, Seattle said it would receive a $5 million milestone payment under that collaboration agreement after the European Medicines Agency decision.

Seattle is also testing the drug in other types of lymphoma.

(Editing by Michele Gershberg, Derek Caney and Andre Grenon)

Groups convince FDA to ease Alzheimer's trial rules (Reuters)

CHICAGO (Reuters) – Academic and industry experts said on Tuesday they have convinced U.S. regulators to ease safety restrictions imposed on clinical trials of Alzheimer's drugs, a move that could improve the chances that a drug being developed jointly by Pfizer and Johnson & Johnson might succeed.

A 2008 study of 240 patients testing that drug, known as bapineuzumab, found a dozen cases of a brain swelling condition called vasogenic edema, shaking confidence in the safety of agents that reduce levels of a protein called beta amyloid that accumulates in the brains of Alzheimer's patients.

That study prompted the U.S. Food and Drug Administration to issue stricter safety guidelines for clinical trials of drugs that alter amyloid in the brain, Maria Carrillo of the Alzheimer's Association said in a telephone interview.

The guidelines restricted patients in the trials to having no more than two incidents of cerebral microhemmorhages, or tiny leaks of blood in the brain, before they enter a study. They also called for frequent MRI scans to check for brain swelling or other problems that might be caused by the study drugs, Carrillo said.

Under new guidelines ironed out through the Alzheimer's Association's Research Roundtable -- which included both industry and academic researchers -- the FDA has now eased those guidelines, Carrillo said in a telephone interview.

Many companies, including Pfizer and J&J and Eli Lilly, are working to develop drugs that reduce levels of this protein.

Carrillo said the new guidelines -- based on the latest research -- recognize that many patients with Alzheimer's disease have had these types of brain events, and excluding so many people from clinical trials would make it more difficult to find effective drugs.

"We were able to bring together all of the literature involved in the discussion of MRI abnormalities that could occur when you are aging with Alzheimer's disease and when you are participating in clinical trials with an amyloid-modifying agent."

Carrillo said the group of industry experts and researchers submitted their report to the FDA, which has adopted the new recommendations. The report was published on Tuesday in the journal Alzheimer's and Dementia.

The new guidelines allow some patients who develop brain swelling to stay in clinical trials, she said.

"We don't want to compromise safety, but we also want to make sure as many people as possible can participate in Alzheimer's clinical trials," Carrillo said.

In January, Eli Lilly said one patient in ongoing trials of the company's drug solanezumab temporarily developed brain swelling, although it was not clear whether the patient was taking the Lilly drug or a placebo. The problem was not seen in a follow-up brain scan and the patient resumed treatment.

Rachel Schindler, an Alzheimer's disease expert at Pfizer who worked on the study and wrote an editorial in the journal, said, "broadening the restrictions would allow a better understanding of the potential risks and benefits of amyloid-lowering treatment."

In May, J&J said it plans to seek U.S. regulatory approval for bapineuzumab in 2012 or 2013, but analysts have said more studies may be needed because of issues with brain swelling.

Currently, there are no drugs that alter the course of Alzheimer's, which affects 26 million people globally and costs more than $600 billion a year to treat.

(Editing by Eric Walsh)

Shire drug for rare swelling worked in trial: FDA (Reuters)

NEW YORK (Reuters) – Shire Plc's drug to treat severe swelling caused by a rare genetic disorder showed effectiveness in a key clinical trial, U.S. Food and Drug Administration staff said on Tuesday.

The injected drug, Firazyr, is under U.S. review for treating attacks suffered by patients with hereditary angioedema.

FDA staff issued a report on the drug, which is approved in other countries, ahead of a federal advisory committee meeting to review the medicine on Thursday.

The clinical trial, known as FAST-3, was conducted to address the FDA's concerns over the drug's efficacy from two earlier studies. The agency declined to approve the drug in April 2008, citing clinical deficiencies.

In FAST-3, Firazyr, or icatibant, showed a statistically significant decrease in time to primary symptom relief, FDA staff said.

"Collectively, the findings from the Phase 3 clinical program support the efficacy of icatibant for the proposed indication," FDA staff said in their documents.

The agency also found no pattern of serious adverse events across the studies that appeared attributable to Firazyr.

The FDA is expected to make a decision on Firazyr by August 25.

Shares of Shire were up 0.6 percent in London.

Hereditary angioedema is a rare and dangerous genetic disease characterized by sudden attacks of swelling in areas such as hands, arms, feet, face or breathing passages. It is estimated to affect one in 50,000 people.

Firazyr is already approved in more than 35 countries in Europe and elsewhere. Analysts on average expect the drug's sales to reach $107 million by 2015, according to Thomson Reuters Pharma, after Shire reported $11 million in Firazyr sales last year. The company reported overall revenue of nearly $3.5 billion in 2010.

Deutsche Bank analyst Mark Clark said he was confident the drug would win approval following the FDA staff release of the documents. Shire initially put Firazyr's sales potential at as much as $450 million, but the U.S. delay and arrival of competitors has dampened expectations, Clark said in a research note.

U.S. sales of Viropharma Inc's Cinryze, a rival drug approved in October 2008, reached $177 million last year, Clark said.

Shire has a significant business in drugs for rare genetic disorders, such as Gaucher disease and Fabry disease.

(Reporting by Lewis Krauskopf; Editing by Lisa Von Ahn)