Replies to post #101151 on Biotech Values

[InTheTrenches]

MNKD:

Recently re-filed their Afrezza (inhaled insulin) NDA.


Anyone here care to handicap their chances of:

- Getting FDA approval on Afrezza by the end of the year.

- Signing a deal on Afrezza before FDA review (they need money)

- Whether Afrezza, if approved, will go the way of Exubera (pulled from market by Pfizer after marketing failure)


No position, but taking a closer look.

TIA

[zipjet]

...it's what happens if standards are written by people completely out of touch with the real world.

That is why we need more regulations written by ever more lawyers and academics. Why should antibiotics be all that grinds to a halt?

ij

PS - I am probably more sick of this stuff than most. I see it much too often, especially coming from judges who are making bad law and then extending the bad law others started.

[flatlander_60048]

Thanks

This is a topic that is generating a lot of ire. It is apparent that the risk to reward is out of whack such that no Pharma can justify the level of trials required by the FDA. I read an article that suggested that the testing could possibly be rationalized if additional years of patent protection were provided to justify the expenditures.

There will be a lot of ugly finger pointing and unfortunate patients will be hurt or killed if this situation is not addressed.

FL

[DewDiligence]

Lawmakers Blast FDA on Non-Inferiority Studies

http://www.reuters.com/article/idCNN276362720100827

›Fri Aug 27, 2010 5:55pm EDT
By Susan Heavey

WASHINGTON, Aug 27 (Reuters) - The U.S. Food and Drug Administration is cracking down on use of certain clinical trials that show a new drug is no worse than another already on the market, according to a government report released on Friday.

Such trials, known as non-inferiority trials, are used when drugmakers want to compare their experimental product to another one that is already FDA-approved. By showing that their new drug is no worse than another, it can also show some potential benefits such as fewer side effects.

But some critics question the benefit of approving a new drug if it is simply shown to be no worse than something already available to patients, especially if any additional benefits are slight.

The report, conducted by the Government Accountability Office and released by a bipartisan group of U.S. lawmakers, found the FDA is taking a tougher line in the wake of industry guidelines it issued in March.

"GAO's review of FDA's guidance showed that the agency has become more conservative in allowing evidence from non-inferiority trials to demonstrate a drug's effectiveness," the report said.

"First, FDA has limited the indications for which these trials may be used. Second, the agency has also become more rigorous in its review of evidence from non-inferiority trials," according to the GAO, which analyzed such trials looked at by the FDA between 2002 and 2009.

Additionally, the GAO said that repeatedly using non-inferiority trials for certain kinds of drugs can lead to "biocreep," in which successive approvals lead to drugs that are less and less effective and eventually "no more effective than a placebo." [Such an outcome can occur because each non-inferiority trial allows the experimental drug to be worse than the comparator by a prespecified “delta” and still be deemed non-inferior to the comparator.]

Drugmakers can work with the FDA to choose from a variety of clinical trial designs when developing a new therapy, but other kinds of studies are not without their weaknesses.

Placebo-controlled trials only prove a drug is better than a sugar pill -- that is, no treatment at all. Superiority trials can show a therapy is better than another one, but can take more time and be expensive, and are tougher to prove.

Proving a drug is actually no worse than another can also be challenging. According to the GAO, "non-inferiority trials are more complicated to design and their results are more difficult to interpret than other types of clinical trials." [Non-inferiority trials also have more room for cheating. To take an extreme case for the sake of illustration, if clinicians agreed in advance to give every patient the same efficacy outcome, the trial would be guaranteed to be a statistical success.]

In March, FDA officials gave pharmaceutical manufacturers advice on how to set up such trials. They can be used to prove a drug is no worse than another in people with certain infections, HIV, cancer and a few other conditions.

FDA objected to using non-inferiority trials in three cases but ultimately approved the drugs: Merck & Co Inc's antibiotic Noxafil, Bristol-Myers Squibb Co's HIV drug, Reyataz and Novartis' anemia drug Exjade. Fifteen other drugs were also approved using such trials during 2002 through 2009, the GAO said.

Democratic lawmakers and Senate Finance Committee ranking Republican Charles Grassley said in a statement the GAO's finding shows the agency needs to proceed with caution when evaluating such trials.

"The GAO report shows that these so-called non-inferiority trials have often proved to be an inferior means of reviewing the safety and efficacy of new drugs," said Representative Ed Markey, a Democrat. [Ed Markey has a strong opinion on many subjects, but I wonder how much he understands about biostatistics. I used to live in Markey’s congressional district.] "While the FDA has made strides to improve evaluations relying on non-inferiority trial data, the GAO report highlights important limitations of non-inferiority trials."

FDA officials had no immediate comment on the report.‹

[genisi]

FRX/ceftaroline (apropos to the FDA guidance and ever-changing goalposts)

Phase III program for ceftaroline was initiated in 2007 under the old FDA standards and the primary efficacy endpoint was noninferiority on symptoms resolution at the test-of-cure visit 7-14 days after EOT. Interestingly, the antibiotic was noninferior to the comparator even under the FDA's new efficacy criteria - cessation of spread of the lesion along with absence of fever at day 3.
Briefing docs:

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM224656.pdf

US FDA staff: Forest antibiotic seems effective

http://www.reuters.com/article/idCNN3127328720100902?rpc=44

* FDA staff back safety, efficacy of ceftaroline

* Advisory panel to review drug on Tuesday

* Forest shares up 5.4 pct in afternoon

* Nearly $361 million in ceftaroline sales seen in 2014

By Lisa Richwine

WASHINGTON, Sept 2 (Reuters) - A Forest Laboratories Inc (FRX.N) antibiotic appears effective with risks similar to current options, U.S. drug reviewers said in an analysis that raised hopes for the medicine's approval.

Shares of Forest, which needs new medicines to offset looming patent expirations on its major drugs, were up $1.49 or 5.4 percent at $29.14 on the New York Stock Exchange after the Food and Drug Administration released its preliminary review on Thursday.

Analysts expect nearly $361 million in sales in 2014 for the potential new antibiotic called ceftaroline, according to Thomson Reuters forecasts.

An FDA advisory panel will review the drug at a public meeting on Tuesday. A positive vote would move the medicine closer to the U.S. market.

In a 70-page analysis released on Thursday, FDA staff said ceftaroline seemed effective for fighting serious skin infections and pneumonia. Potential side effects were similar to alternative treatments, they said.

"FDA appears to go into the panel with a positive bias toward approval" for both conditions, Robert W. Baird analyst Thomas Russo said in a research note. He predicted the stock would close $1 to $2 higher on Thursday.

Ceftaroline is one of six medicines in late-stage development that Forest says will more than replace the coming revenue losses from patent expirations on flagship antidepressant Lexapro and Alzheimer's treatment Namenda.

The company reported net revenue of nearly $4.2 billion for the fiscal year ended March 31.

Ceftaroline is an intravenous antibiotic developed to fight serious and possibly life-threatening infections including methicillin-resistant Staphylococcus auereus (MRSA), a growing public health threat.

FDA staff analyzed Forest's data from two clinical trials in adults with bacterial pneumonia acquired outside a hospital setting. The agency reviewers said their analysis "supported the efficacy conclusions" from Forest that the drug worked as well as an older antibiotic, ceftriaxone.

The drug also appeared equivalent to a combination of the antibiotics vancomycin and aztreonam in two studies of adults with complicated skin infections, FDA staff said.

Ceftaroline is a new medicine in the cephalosporin class of antibiotics that have been used for decades.

The most common possible side effects include diarrhea, headache, nausea and insomnia.

In a separate summary prepared for the advisory panel, Forest said new antibiotics were needed to fight resistant infections that do not respond to current treatments.

"Ceftaroline addresses these distinct areas of unmet medical need," the company said.

The FDA will consider the advisory panel's input when it decides in the coming weeks whether to approve the drug. The agency usually follows panel recommendations.

Forest obtained rights to ceftaroline with its 2007 purchase of privately held biotech company Cerexa Inc. Swiss drugmaker AstraZeneca (AZN.L) is co-developing the drug in markets outside the United States, Canada and Japan. Takeda Pharmaceutical Co (4502.T) holds the rights in Japan.