Orange Book Blog

Teva Pulls Generic Biaxin XL Off the Market Following Emergency Motion Filed by Abbott

In response to an emergency motion for preliminary injunction enforcement filed by Abbott Laboratories on June 26 in the U.S. District Court for the Northern District of Illinois, Teva Pharmaceuticals USA, Inc. announced on June 27 that it will cease sales of a generic version of Abbott's Biaxin XL (clarithromycin extended release), which Teva had initiated following a June 22 decision by the U.S. Court of Appeals for the Federal Circuit vacating the district court's June 2005 preliminary injunction order.  As previously reported here, a divided Federal Circuit panel held that Teva had raised substantial questions as to the validity of Abbott's patents covering Biaxin XL, and thus vacated the preliminary injunction order.

Abbott's emergency motion asserted that the preliminary injunction order remained in effect until the Federal Circuit issued a mandate to the District Court, which would generally not occur until at least 21 days following entry of the Federal Circuit's judgment.  Abbott's motion noted that this time period is likely to be further extended, as it intends to file a petition for rehearing, which would automatically stay the mandate until disposition of the petition.  Abbott's motion requests the District Court not only to order Teva to comply with the preliminary injunction order, but also to hold Teva in contempt and sanction it for violating the preliminary injunction order.

In a June 27 press release, Teva announced that Abbott agreed to a briefing schedule concluding on June 29 and that Teva agreed to refrain from further sales of this product pending the outcome of the motion. Teva's response in pulling its generic Biaxin XL off the market after approximately 3-4 days is puzzling, as one would assume that the issues raised by Abbott in its motion were fully considered by Teva prior to market entry.

Teva's response also serves to undercut at least one argument made by generic rival Andrx Pharmaceuticals, in its June 26 motion to vacate the District Court's preliminary injunction order entered against it.  Andrx was also sued by Abbott in the Northern District of Illinois over the same Biaxin XL patents that Teva was sued on.  In a consolidated order in November 2005, the district court preliminarily enjoined Andrx and Ranbaxy from selling a generic equivalent of Biaxin XL.  Appeals to the Federal Circuit by Ranbaxy and Andrx are pending.  In its motion to vacate the District Court's preliminary injunction order, Andrx argued (in part) that, given generic entry into the Biaxin XL market by Teva, Abbott was no longer entitled to a presumption of irreparable harm. At least for now, that argument appears unavailing.

Senators Introduce Bill to Ban Reverse Payment Settlements of Hatch-Waxman Cases

In response to the Supreme Court's denial of certiorari in FTC v Schering earlier this week, four senators introduced Senate bill S3582 yesterday, which seeks to prohibit brand name drug companies from entering into "reverse payment" settlements with generic drug companies.  In FTC v. Schering, the FTC had petitioned the Court to decide whether a reverse payment settlement from Schering to generic drug makers was in violation of antitrust laws.  Denial of certiorari by the Supreme Court left standing an Eleventh Circuit decision holding that the settlement did not violate antitrust laws.

S3582 was introduced by Senator Kohl (D-WI); co-sponsors were Senators Leahy (D-VT), Grassley (R-IA), and Schumer (D-NY).  In Sen. Kohl's press release announcing introduction of the bill, its sponsors decried the effect that reverse payment settlement agreements have on market entry of lower-cost generic drugs, asserting that such settlement agreements undermine true competition, and thus should not be allowed.

The current version of S3582 would amend Section 5 of the Federal Trade Commission Act (15 U.S.C. 45) by adding a new sub-section making it an unfair method of competition for "a person, in connection with the sale of a drug product, to directly or indirectly be a party to any agreement resolving or settling a 'patent infringement claim' in which (a) an ANDA filer receives anything of value; and (B) the ANDA filer agrees not to research, develop, manufacture, market, or sell the ANDA product for any period of time."

The proposed bill would exclude from its reach any agreement in which the value paid to an ANDA filer by the NDA holder "includes no more than the right to market the ANDA product prior to expiration of the patent that is the basis for the patent infringement claim." The bill defines "patent infringement claim" to be "any allegation [of possible patent infringement] made to an ANDA filer, whether or not included in a complaint filed with a court of law."  The statute thus seeks to reach beyond reverse payment agreements resolving patent infringement litigation, to include pre-litigation settlement agreements as well.

S3582 has been referred to the Committee on Commerce, Science, and Transportation.

NOTE:  Thanks to a Kohl staffer for providing an advance copy of the bill.

PhRMA Study Finds Authorized Generics Lead to Lower Drug Prices

The Pharmaceutical Research and Manufacturers of America (PhRMA), the trade group representing innovator drug companies, released a new study yesterday concluding that authorized generic drugs lead to lower drug prices for consumers.  PhRMA commissioned IMS Consulting to conduct the study.

According to PhRMA's press release announcing the study:

The analysis examined case studies with and without authorized generics and found that with an authorized generic on the market during the exclusivity period, discounts to brand medicines were greater--on average 15.8 percentage points greater--than instances when a generic company did not face competition from an authorized generic.

The most common criticism of authorized generics is that they reduce incentives for generic drug companies to develop generic drugs in the first place, by diminishing their profits during the 180-day exclusivity period.  Generic drug makers would likely criticize PhRMA's new study on the basis that it does not examine the long-term effects of authorized generics, which might include fewer generic drugs becoming available.

As reported previously on this blog, the FTC is undertaking its own study of authorized generics and expects to complete its study sometime next year.

UPDATE:

• 28 June 06 Response from Generic Pharmaceutical Association

Supreme Court Denies Certiorari in FTC v. Schering: reverse payment settlement of Hatch-Waxman case avoids antitrust scrutiny by high court

The Supreme Court this morning denied review of FTC v. Schering, without comment.  The FTC had petitioned the Court to decide whether a "reverse payment" settlement from an innovator drug company to a generic drug maker in a Hatch-Waxman case violated the antitrust laws.  Denial by the Supreme Court leaves standing an Eleventh Circuit ruling that the settlement was legal.

Earlier, the Court had asked the Department of Justice for its views on the case, and the DOJ filed a brief advising the Court to deny review.  The FTC then filed a supplemental brief asking the Court to at least hold the case pending the outcome of In re Tamoxifen Citrate Antitrust Litigation, which is currently on petition for rehearing en banc in the Second Circuit.  That case involves a similar reverse payment settlement of Hatch-Waxman litigation.

The FTC is no doubt bitterly disappointed that the Supreme Court denied its cert petition.  Last month, the FTC Commissioner sounded a warning that if the Court denied review, drug companies "will have carte blanche to avoid competition and share resulting profits, and we will see minimal competition before patent expiration."

RELATED READING:

• 26 June 06 Wall Street Journal article
• 26 June 06 Washington post article
• previous Orange Book Blog posts on FTC v. Schering:  19 June 06; 26 May 06; 19 May 06; 9 May 06

FDA Appeals Omnitrope Case to D.C. Circuit

The FDA recently appealed the district court case that forced it to make a decision on Sandoz's drug application for Omnitrope, which later led to FDA to approve Omnitrope.  Sandoz has called Omnitrope the first ever biogeneric drug.

In a decision on April 10, the U.S. District Court for the District of Columbia held, on summary judgment, that 21 U.S.C. 355(c) requires the FDA act on a new drug application within 180 days of receiving it.  More specifically, within 180 days the FDA must either approve the new drug application or give the applicant notice of an opportunity for a hearing.

The FDA did not deny that it did neither of those things.  Instead, the FDA argued that the statute was aspirational rather than mandatory.  The FDA argued in the alternative that the court should respect the autonomy of the executive branch and let the FDA set its own priorities.

IN OTHER BIOGENERICS NEWS, FDANews is running a story tomorrow quoting a Senate staffer who said that Congress would likely not take up legislation establishing a regulatory pathway for biogenerics until 2008.

RELATED READING:

• previous Orange Book Blog posts on Omnitrope:  1 June 06 and 4 June 06

NOTE:  thanks to Kurt Karst for providing a copy of the FDA's Notice of Appeal.

FDA Grants Final Approval to Ivax and Ranbaxy for Generic Zocor

The FDA today granted final approval to Ivax and Ranbaxy to market generic versions of Zocor (simvastatin).  Additionally, it appears the FDA has granted generic marketing exclusivity to Ivax and Ranbaxy for the next 180 days.

The FDA approval comes despite a last-ditch effort by Novartis subsidiary Sandoz to prevent the FDA from granting final approval and marketing exclusivity to Ivax and Ranbaxy.  Earlier today, the U.S. District Court for the District of Columbia refused to grant Sandoz's request for a temporary restraining order against the FDA.

In a press release announcing the approval, the FDA stated, "This approval is another example of our agency's efforts to increase access to safe and effective generic alternatives as soon as the law permits."  The FDA has appealed a district court ruling that required the FDA to grant final approval to Ivax and Ranbaxy today, the day Merck's final patent on Zocor expired.  That appeal is still pending before the D.C. Circuit.

RELATED READING:

• 23 June 06 MarketWatch.com story
• 23 June 06 Reuters article

UPDATES:

• 24 June 06 Bloomberg story:  Insurance Companies Push Generic Zocor
• Dr. Reddy's launches authorized generic Zocor

Federal Circuit Vacates Preliminary Injunction Against Teva Relating to Generic Version of Abbott's Biaxin XL (Clarithromycin Extended Release)

In a 31-page opinion by Judge Prost, joined by Judge Gajarsa, a Federal Circuit panel held yesterday that Teva had raised a substantial question as to the validity of Abbott's patents covering its extended release clarithromycin product, Biaxin XL, and therefore vacated a preliminary injunction that had been entered against Teva by the U.S. District Court for the Northern District of Illinois.

Clarithromycin is used to treat bacterial respiratory infections.  Annual sales of Biaxin XL are approximately $255 million.

The majority opinion found that Teva had raised a substantial question that the patent in suit was obvious.  For example, with respect to two claims covering extended release formulations of clarithromycin, the court held that Abbott's own prior art patent on azithromycin compositions rendered the clarithromycin claims of the patent in suit obvious.  In reaching this holding, the majority inferred an "admission" from Abbott's prior art patent (the '190 patent):

We presume that Abbott filed and prosecuted the '190 patent respresenting that claim 14 of the '190 patent [directed to azithromycin compositions] satisfies the written description and enablement requirements of 35 U.S.C. 112.  See Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313 (Fed. Cir. 2003) ("We hold a presumption arises that both the claimed and unclaimed disclosures in a prior art patent are enabled.").  Because the '190 patent explicitly discloses only clarithromycin controlled release compositions, yet claims azithromycin compositions, we conclude that Abbott has represented to the [patent office] that the differences between clarithromycin and azithromycin were such that azithromycin could be substituted into a controlled release clarithromycin composition by a person of ordinary skill in the art without undue experimentation.

Judge Newman wrote a 9-page dissent in which she characterized the majority opinion as a "de novo and incorrect contrary ruling."  She stated, "My colleagues ignore the district court's analysis, offering neither deference nor acknowledgement."  Specifically, Judge Newman said the court should have deferred to the district court's finding that the substitution of azithromycin with clarithromycin was merely "obvious to try."  She wrote, in summary, "My colleagues conclude that claim 4 of the [patent in suit] is 'vulnerable to allegations of invalidity,' and find 'a substantial argument' as to other claims.  These are not the criteria of likelihood of success."

The suit was initiated in March 2005.  A bench trial is scheduled for March of next year.  Teva has yet not indicated when it intends to launch its generic version of Biaxin XL.

Sandoz Requests TRO to Block FDA Approval of Generic Zocor Tomorrow

Bloomberg News is reporting tonight that Sandoz, the generics arm of Novartis AG, filed a request for a temporary restraining order today in an attempt to prevent the FDA from granting Ivax and Ranbaxy final approval tomorrow to market generic Zocor (simvastatin).

The motivation behind Sandoz's eleventh hour request is not entirely clear, especially because it appears from the FDA website that Sandoz does not have an ANDA on file to market its own generic version of Zocor.  In the Bloomberg News article, Sandoz seems to explain that it filed its TRO request in order to avoid a precedent that might affect other ANDA approvals in the future.  However, that justification seems suspicious--the FDA has appealed the district court decision that effectively ordered the FDA to grant final approval to Ivax and Ranbaxy, and the appeal is on an expedited schedule.  If the FDA's appeal is successful, the precedent Sandoz fears would be avoided.

Besides Ivax and Ranbaxy, the other simvastatin ANDA applicants are Aurobindo, Cobalt, and Teva.  Ivax is itself a unit of Teva.

According to the Bloomberg News article, a hearing is scheduled for 10 a.m. tomorrow in the U.S. District Court for the District of Columbia to decide Sandoz's request for a TRO.  Teva says it will vigorously fight Sandoz's request.

UPDATES:

• 23 June 06 MarketWatch.com story
• 23 June 06 Reuters article

Merck Launches Pre-Emptive Strike Against Generic Zocor

In advance of Merck's patent on Zocor expiring tomorrow (Friday), and the expected launch of generic versions of Zocor by Ivax (a Teva unit) and Ranbaxy, Merck has made deals with some insurance companies to sell branded Zocor for less than Ivax and Ranbaxy planned to charge for their generics.  Teva's stock price dropped about 10% yesterday on the news.  And Sen. Charles Schumer (D-NY) announced that he has written a letter to the FTC, requesting an investigation of Merck.

With Zocor going off-patent, Merck had already planned to stem its losses by cutting a deal with Dr. Reddy's to sell an authorized generic version of Zocor.  Now, in this new strategy (new to me, at least--please let me know if you've heard of it before), Merck plans to take on the generics directly by offering its branded drug for less than the generics.

Many good articles have been written about this in the last couple days.  Here are a few:

• Associated Press
• Bloomberg News
• MarketWatch
• Motley Fool
• Reuters
• TheStreet
• USA Today
• Wall Street Journal

Also, an Israeli business website, Globes, has published this very interesting interview with Teva CEO Isreal Makov regarding Merck's surprising move.

Bill Proposed in House to Provide Escape for Late Patent Term Extension Filings

After a Massachusetts drug company missed--by a single day--a non-extendable deadline for filing for a patent term extension, H.R. 5120 was recently proposed in the U.S. House of Representatives to amend 35 U.S.C. 156, the statute governing patent term extensions based on regulatory review delay.  Some people are calling H.R. 5120 the "Dog Ate My Homework Act."

Under the current version of 35 U.S.C. 156, a patent applicant has 60 days after approval under the relevant regulatory review (generally FDA review and approval of new drugs) in which to submit an application to the U.S. Patent Office for patent term extension; no allowance is made for a late filing.  H.R. 5120 would amend 35 U.S.C. 156 to provide the U.S. Patent Office with discretion in accepting late applications, so long as (a) the application was filed within 5 days after expiration of the 60-day period, and (b) the delay was unintentional.

As drafted, the amendment would go into effect on the day of its enactment, and would apply not only to applications for patent term extension pending on or filed after the date of enactment, but also to those applications which are "the subject of a request for reconsideration of a denial of a patent term extension," such as the Medicine Company's, or which have "been denied a patent term extension . . . in which the period for seeking reconsideration of such denial has not yet expired."

The 2005 Medicines Company annual report indicates that the company continues to explore alternatives to extend the term of the patent.  If enacted as proposed, H.R. 5120 might be such an alternative.

The Medicines Company, based in Massachusetts, licensed a patent owned by Biogen covering the drug Angiomax and its use in preventing blood clots from forming during angioplasty.  The Medicines Company application for a patent term extension was filed on the 61st day following FDA approval of Angiomax; as a result, the U.S. PTO denied the request for patent term extension.  The Medicines Company has filed a request for reconsideration of the application for patent term extension.  A copy of the file history of the relevant patent, including the application for patent term extension, decision on the petition, and request for reconsideration, can be found here.

The House bill was sponsored by Representative Jenkins (TN), and co-sponsored by Representatives Andrews (NJ), Delahunt (MA), Frank (MA), Hyde (IL), Meehan (MA), Sessions (TX), Boucher (VA), Duncan (TN), Gallegly (CA), Jones (OH), and Rothman (NJ).  The bill has been referred to the House Committee on the Judiciary.

RELATED READING:

• AP story on H.R. 5120