Replies to post #15492 on Biotech Values

[DewDiligence]

More on the NVS lawsuit against the FDA:

[For readers of this board, most of this article is probably old news.]

http://online.wsj.com/article/0,,SB112664326873039592,00.html

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Novartis Unit Sandoz Sues FDA
Over Biotech Growth Hormone

By ANNA WILDE MATHEWS
Staff Reporter of THE WALL STREET JOURNAL
September 13, 2005 4:48 p.m.

Escalating a high-stakes fight over how to produce generic copies of biotechnology drugs, a unit of Novartis AG sued the Food and Drug Administration over the agency's refusal to approve its copycat version of human growth hormone.

Sandoz, a generics maker owned by the Swiss pharmaceutical giant, filed a suit against top officials of the FDA and its parent agency, the Department of Health and Human Services, in U.S. District Court in Washington, D.C., yesterday. The suit argued that agency officials violated U.S. federal law through their "failure to perform their nondiscretionary duty to act upon the fully FDA-reviewed new drug application" for Omnitrope, and it asks the court to force FDA to make a decision about the drug.

The suit throws into court one of the most sensitive scientific and policy issues facing regulators and the drug industry: creating low-cost copies of some of the most complicated, expensive and important treatments for cancer and other diseases.

There are a number of human growth hormone products on the market, made by companies that include Genentech Inc., Eli Lilly & Co. and Pfizer Inc., which petitioned the FDA to reject Omnitrope.

The patents on the oldest biotech drugs are beginning to expire, but the U.S. Congress hasn't defined a clear legal pathway to win U.S. approval for generic versions of biotech drugs, like the one that exists for traditional chemically based medicines. That spares biotech companies the competition of knockoffs and also prevents the price breaks that such rivalries bring.

Because of a bureaucratic quirk, a handful of biotech products, including human growth hormone and insulin, wouldn't require a change in the law for copies to get through the FDA. The FDA said early last year that it planned a process to clarify the scientific issues surrounding such products -- which it calls follow-ons, not generics -- but so far, the agency has made little public progress in issuing regulatory guidelines.

The issue will only gain more attention as biotech drugs -- which include many of the most innovative treatments for life-threatening diseases -- represent a bigger portion of the world's medical bills. An FDA approval of Omnitrope, or a court ruling forcing the agency to take action, could open the door to more biotech copies, a prospect eagerly sought by companies, including Barr Pharmaceuticals Inc.

Last September, the FDA told Sandoz that it was unable to reach a final decision on Omnitrope because of uncertainty about scientific and legal issues, according to Sandoz. In its suit, the company argued that the agency "lacked any basis in fact or law upon which to deny approval" of Omnitrope. The FDA's professional staff advised the company about what studies to do, the suit says, and data prove that Omnitrope is "safe and effective for its intended use" and "indistinguishable" from Pfizer's Genotropin product.

Moreover, the suit argues that for the small group of biotech products that fit the bureaucratic quirk, the FDA's rules don't make any distinction between traditional drugs and biotech products. The company argues that the FDA has effectively approved drugs derived from biologic materials before. The suit also says that in reviewing Omnitrope, the FDA didn't have to rely on any confidential data from Pfizer's application for its human growth hormone product, Genotropin.

European regulators, which like the FDA are struggling with how to move forward with copies of biotech drugs, have also stalled Omnitrope. Sandoz is protesting that move as well.

For two decades, generic makers of traditional, chemically based drugs -- such as Eli Lilly's Prozac -- have been able to shortcut the FDA-approval process by relying on data generated by the original manufacturer. That opening was defined by a landmark 1984 law. So far, though, U.S. lawmakers have taken little action toward a similar legislative fix for generic biotech drugs.

The issue has generated a bitter political and regulatory clash. Biotech companies argue that their medicines are too complex for others to duplicate without performing the extensive tests conducted on the original products and also raise concerns about whether it is legitimate for generic competitors to rely on their research. On the other side, generic makers maintain that they can make safe, effective copies of biotech drugs -- just as they do with chemically based drugs -- without replicating all of the brand makers' work, which requires many years and millions of dollars.

Traditional drugs are easier to duplicate than biotech medicines, in part because making the active ingredients typically involves well-understood chemical processes. Biotech medicines, by contrast, are generally produced by splicing a genetic sequence that corresponds to a particular protein, such as human insulin, into living cells.

The proteins in biologic medicines are much larger and less well understood than traditional drug molecules. In addition, proteins made in different cell lines, or even in different manufacturing facilities, can behave very differently as medicines, exhibiting unexpected side effects or requiring different dosing.
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[DewDiligence]

Judge Sides With Novartis Against FDA

[In the Omnitrope (generic hGH) case, the court tells FDA: fish or cut bait!]

http://online.wsj.com/article/SB114504238943426304.html

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FDA Is Ordered to Rule On Generic Biotech Drug

By ANNA WILDE MATHEWS
April 15, 2006

A federal judge ordered the Food and Drug Administration to rule on a human growth hormone product made by a Novartis AG unit, adding pressure for the agency to deal with the high-stakes question of generic copies of biotechnology drugs.

The decision by Ricardo M. Urbina, a judge in the U.S. District Court for the District of Columbia, came in response to a suit filed by Sandoz, a generics unit of Novartis, a Swiss pharmaceuticals maker [#msg-7723132]. The suit, which named top officials of the FDA and its parent agency, the Department of Health and Human Services, alleged that the agency violated federal law by failing to either approve or reject Sandoz's July 2003 application to market Omnitrope, a version of human growth hormone.

The judge's opinion issued Monday -- saying the agency is required to meet a statutory deadline in its decisions on whether to approve drugs -- could strengthen the hands of drug companies. Judge Urbina wrote that the FDA had "identified no compelling reason for this court to excuse its delay."

Sandoz's application "remains stuck in the ether," the judge wrote, citing the "egregiousness of the delay." The opinion says the FDA must meet statutory requirements, which include the option of giving the company a hearing before the Secretary of Health and Human Services about whether its drug is approvable.

Sandoz said in a statement it "looks forward to FDA's decision and expects a positive outcome." An FDA spokeswoman said the agency is evaluating the decision and considering next steps.

The FDA's decision on Omnitrope is being closely watched as a sign of how FDA will move forward on the broader question of generic biologics. The patents on the oldest biotech drugs are beginning to expire, but pressure from the generics industry has yet to move Congress to define a clear legal pathway to win U.S. approval for generic versions of products that now are some of the most important and expensive medications on the market.

For historic reasons, a handful of biotech products, including human growth hormone and insulin, wouldn't require a change in the law for copies to get through the FDA, though the FDA hasn't yet issued regulatory guidelines on how this will work. Last month, in a letter to Sen. Orrin Hatch, a Utah Republican, and Rep. Henry Waxman, a California Democrat, the agency said its work on follow-on versions of those products "has not stalled" but didn't give a planned timeline on when broader guidelines might come out.

The generics industry is prodding for action on generic biotech drugs, but has been opposed by some big biotech and drug companies. Still, the momentum in the industry may shift: An official from Pfizer Inc., which opposed approval of a copy of its Genotropin human growth hormone, said publicly last month that the company may explore generic biologics.
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[DewDiligence]

Major story: FDA Approves NVS’ rhGH under Section 505b2

[Although drugs approved under Section 505b2 are not true generics because they are not substitutable at will for a branded reference drug, the FDA’s approval of NVS’ Omnitrope is nevertheless a significant milestone in that it’s the FDA’s first approval of a copycat drug made using recombinant technology.

NVS’ application had been languishing at the FDA for almost three years! NVS got tired of waiting, sued the FDA in federal court (#msg-7723132), and won: the court ordered the FDA to fish or cut bait, and now the Agency has reluctantly decided to fish.]

http://online.wsj.com/article/SB114904669181067236.html

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By ANNA WILDE MATHEWS
May 31, 2006 12:05 a.m.

The Food and Drug Administration approved a copycat version of human growth hormone made by a unit of Novartis AG, a closely watched decision amid debate over how to move toward generic biotechnology drugs.

The approval of Sandoz's Omnitrope, which became public late Tuesday night through a posting on the FDA's Web site, is important because it confirms that the FDA has the scientific knowledge to approve a so-called "follow-on" version of at least a simple biotechnology drug. Sandoz has said its product is similar to Pfizer Inc.'s Genotropin, and Pfizer filed a petition opposing approval of Omnitrope.

Still, the agency didn't rate Omnitrope as equivalent to Genotropin, as it does with generic versions of traditional chemically derived drugs. [I.e. Omnitrope is not automatically substitutable for Genotropin and hence a prescription must explicitly specify Omnitrope in order for a patient to end up with Omnitrope.] A spokeswoman for Sandoz declined comment.

The FDA downplayed the decision in the document posted on its Web site, saying it "does not establish a pathway" for approval of other follow-on biotech drugs. The agency has said that Congress must change the law before it can approve any copies of nearly all other biotech products, and lawmakers haven't moved on the issue.

For historic reasons, a handful of biologic products, including human growth hormone and insulin, are regulated differently than the rest and do not require a change in the law for FDA to approve follow-on versions. "This was reviewed under a part of the statute that allows for approval of a follow-on protein but the FDA doesn't have the legal authority or a pathway to approve a generic biologic," an agency official said late Tuesday night.

In addition, the FDA official said that Sandoz "did not rely on proprietary information contained in the Genotropin application." He said Sandoz used publicly available information about the Pfizer product, along with its own studies, to demonstrate that Omnitrope was safe and effective.

That was a key question raised by Pfizer, which argued that Sandoz could not rely on nonpublic findings about Genotropin to win approval for Omnitrope. Other biotech companies have also objected to the idea of generics makers relying on data in their applications to win approval for copies.

The agency also noted in its posting that it has approved follow-on versions of other drugs derived from biologic sources. But Omnitrope appears to represent the first time the agency has approved a copycat version of a true "recombinant" biotech drug, or one grown by the manufacturer in living cell lines. Generic biotech drugs are a prospect eagerly sought by generics makers and opposed by much of the biotech industry, which hasn't had to face competition from lower-priced copies even as its products have become some of the most important and expensive medicines. Omnitrope became a significant skirmish in the broader lobbying battle over the issue.

Sandoz, which originally filed its application in July 2003, sued the FDA over its delay of a decision on the product, winning an April ruling from a federal judge that the agency must give an answer. The approval is a win for the aggressive approach taken by Sandoz. Omnitrope had already won approval from European and Australian regulators.

In the U.S., several human growth hormone products are already on the market, made by companies including Eli Lilly & Co. and Genentech Inc., but according to industry officials, each of those drugs had to be approved independently as a full new application.

The question of what studies generics makers have to do in order to sell new versions of biotech drugs is at the heart of the conflict between the generics and biotech industries. Traditional chemically based drugs are easier to duplicate than biotech medicines. Making the active ingredients typically involves well-understood chemical processes. Biotech medicines, by contrast, are generally produced by splicing a genetic sequence that corresponds to a particular protein, such as human insulin, into living cells. The proteins in biologic medicines are much larger and less well-understood than traditional "small-molecule" drugs.

Biotech makers have sometimes argued that because their products are so complicated to make, and the process is proprietary, a generics maker would essentially have to test a copy with all the same costly trials that led to approval of the original – thus removing the price advantage of a generic. For their part, generics companies say that they can manufacture safe, effective versions of existing biotech drugs without duplicating all of the original research.
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