Orange Book Blog

At the intersection of Patent and FDA Law

Recent Posts

  • ViroPharma Pursues Citizen Petition to Block FDA Approval of Generic Vancomycin

    The FDA recently posted ViroPharma, Inc.'s scientific supplement to its citizen petition asking FDA to stay approval of generic Vancocin (vancomycin hydrochloride).  Vancocin is ViroPharma's orally administered tricyclic glycopeptide antibiotic derived from Amycolatopsis orientalis that is approved for treatment of colitis caused by susceptible bacteria.  There are no unexpired patents or other exclusivities available for Vancocin.

    ViroPharma filed its citizen petition March 17, 2006, asking FDA to stay approval of any ANDAs that reference Vancocin capsules based solely on in vitro bioequivalence testing.  This was in response to the FDA Office of Generic Drugs (OGD) announcement that in vivo clinical trials would not be required to establish bioequivalence of generic vancomycin hydrochloride capsules.

    On May 31, 2006, ViroPharma submitted a first supplement to its petition, setting forth its legal arguments that OGD's new standard cannot be used in the review or approval of generic vancomycin.  These legal arguments included alleged OGD violations of the Freedom of Information Act, the Data Quality Act, and the Administrative Procedures Act with respect to implementation of its new in vitro test for Vancocin bioequivalence, as well as asserted legal problems with the test itself.

    The recent scientific supplement to ViroPharma's petition sets forth scientific and clinical arguments regarding the asserted inadequacy of OGD's in vitro test.  Among its arguments, ViroPharma places special emphasis on the complexity of Vancocin and the life-threatening nature of the indications for which it is approved, and the need for comparative clinical trials to establish bioequivalence.

  • GPhA Releases Its Own Study On Authorized Generics

    The Generic Pharmaceutical Association (GPhA), the trade group representing generic drug makers, released a study today concluding that authorized generics do not save consumers money and ultimately will lead to higher drug prices.  GPhA’s study, conducted by a law professor and an economics professor, appears to be a reaction to PhRMA’s study, released last month, reaching the opposite conclusion.

    According to GPhA’s press release, its study:

    conclusively demonstrates that the anti-competitive brand pharmaceutical practice of introducing authorized generics (AGs) "significantly reduce incentives for independent generic firms to challenge invalid brand name patents and to develop non-infringing processes."  This analysis also raised serious questions about the validity of a recent PhRMA study on authorized generics, noting that the PhRMA study contained significant errors making its conclusions questionable at best.

    In response, PhRMA issued its own press release today, defending its study as sound.

  • FDA Updates Status of Its Response to Zocor Citizen Petitions

    The FDA recently published a letter to attorneys representing generic drug companies who filed citizen petitions relating to their ANDAs for generic Zocor.

    The three-page letter essentially ties up some loose ends that remained after the District of Columbia’s April 30, 2006 decision holding that it was unlawful for the FDA to deny IVAX and Ranbaxy’s citizen petitions to relist in the Orange Book two Merck patents covering Zocor.  While the FDA has appealed that decision to the Court of Appeals for the District of Columbia, and the appeal has been granted expedited review, in the meantime the FDA relisted the two Merck patents and granted 180 day market exclusivity to the first ANDA filers, IVAX and Ranbaxy.

    IVAX, a division of Teva, and Ranbaxy launched their generic Zocor products last month when Merck’s last patent on Zocor expired and they were granted final approval by the FDA.

  • Senators Introduce Bill to Ban Authorized Generics During 180 Day Exclusivity Periods

    Senators Jay Rockefeller (D-WV), Patrick Leahy (D-VT), and Charles Schumer (D-NY) introduced a bill, S. 3695, last Thursday that would ban the sale of authorized generic drugs during the first ANDA filer’s 180 day exclusivity period.  The bill was introduced just hours after the Senate Special Committee on Aging held a hearing entitled "The Generic Drug Maze: Speeding Access to Affordable Life-Saving Drugs."  Authorized generics were a hot topic at the hearing.

    Also last Thursday, Sen. Rockefeller issued a press release in which he lauded the efforts of Mylan Laboratories, based in his home state of West Virginia, for its efforts toward fighting authorized generics.  In the release, Sen. Rockefeller states that Hatch-Waxman grants the first ANDA filer "180 days of exclusive market rights, which is just a fraction of the up to 20 years of exclusive market rights given to brand companies."  Sen. Rockefeller doesn’t mention that brand companies, in contrast to generic drug makers, obtain their market exclusivity through patents on their inventions.

    The D.C. Circuit and, more recently, the Fourth Circuit have both upheld the legality of authorized generics.  Therefore, legislation will be necessary if generic drug makers hope to end the practice.

    RELATED READING:

  • FTC Commissioner Testifies on Barriers to Generic Market Entry Before Senate Special Committee on Aging

    FTC Commissioner Jon Leibowitz testified yesterday before the Senate Special Committee on Aging, stating that there continue to be competitive problems in pharmaceutical markets.  The FTC released its prepared statement, which included discussion of:

    • anticompetitive patent litigation settlements (such as reverse payment settlements) between brand pharmaceutical manufacturers and generic competitors;
    • how brand companies have used the 180-day exclusivity period for the first generic paragraph IV certification filers to block generic market entry;
    • anti-competitive agreements between generic companies that delay generic competition; and
    • the FTC's plan to study the impact of authorized generics on pharmaceutical markets.

    Commissioner Leibowitz stated that, due to its enforcement efforts, the FTC was unaware of "any pharmaceutical settlements between a brand-name manufacturer and a generic [paragraph IV certification] filer that included both a payment to the generic company and an agreement by the generic company not to market its product between 2000 and the end of fiscal year 2004."  (It is not clear whether this statement was intended to mean that no such settlements were entered into between 2000 and 2004, or to refer only to settlements where the generic company agreed not to market its product between 2000-2004.)

    The Commissioner bemoaned the recent decision on reverse payments by the 11th Circuit (cert denied by the US Supreme Court) in FTC v Schering, as well as the 2nd Circuit's Tamoxifen decision, arguing that they will invite the type of collusive reverse payment agreements that FTC enforcement had been effective in reducing.  As a result, the FTC supports a legislative solution, such as S 3582 (see also this earlier Orange Book Blog post). 

    The Commissioner also asserted that the 180 day exclusivity period, meant to reward generic filers that challenged weak patents, is increasingly being used as a means to prevent generic market entry via settlement agreements between brand manufacturers and first generic filers, in which the first generic filers agree to delay market entry, and thus initiation of the 180 day exclusivity period.  As a result, subsequent generic ANDA filers are unable to enter the market.

    The Commissioner urged Congress to adopt legislation providing that dismissal of an action brought by a generic applicant seeking a declaratory judgment of invalidity or unenforceability of a patent covering the brand drug constitutes a forfeiture event for the 180 day exclusivity period.

    RELATED READING:

  • District Court Finds Forest Labs’ Lexapro Patent Valid and Enforceable, Halting Teva’s Plans for Generic

    The U.S. District Court for the District of Delaware released its opinion last Thursday in the Lexapro patent infringement case, finding in favor of Forest Labs.  Forest, the maker of Lexapro, sued IVAX, a division of Teva, for patent infringement based on IVAX’s ANDA to market generic versions of Lexapro.  Forest took in over $2 billion on Lexapro sales in the U.S. last year.

    Post-trial briefing in the case was completed not even two months ago.  The quick decision by Judge Farnan suggests the case was a slam-dunk for Forest.

    Addressing defendants’ lead argument, the court found the patent in suit, covering substantially pure (+)-citalopram, was not anticipated by a reference (Smith) that disclosed both the (+) and (-) enantiomers individually.  According to the court:

    Smith only discloses the chemical structure of (R)-citalopram and does not disclose the chemical structure of (S)-citalopram, which corresponds to (+)-citalopram.  In addition, Smith does not disclose anything with regard to the purity of the (S)-enantiomer when it mentions that enantiomer, and the Court cannot presume that the disclosure of (R)-citalopram, individually and not in any mixture, necessarily discloses substantially pure (S)- or (+)-citalopram.  In these circumstances, the Court cannot conclude that Smith discloses the entirety of the claimed invention.

    Earlier last week, Forest Labs sued Caraco Pharmaceutical Laboratories, another generic drug company who filed an ANDA for generic Lexapro.  That case was filed in the Eastern District of Michigan.

    With last week’s decision finding Forest’s patent on Lexapro valid and enforceable, generic drug makers will likely have to wait until 2012 before they can market any generic versions of Lexapro.  Forest’s patent expires in 2011, but its pediatric exclusivity period runs until March 13, 2012.

    Teva will probably appeal the case to the Court of Appeals for the Federal Circuit.

    RELATED READING:

  • Sandoz’s Motion for Preliminary Injunction to Delay FDA Approval of Generic Zocor is Denied

    The District Court for the District of Columbia today denied Sandoz’s motion for a preliminary injunction, filed June 22, 2006, to delay final FDA approval of Teva and Ranbaxy’s generic versions of Zocor.  Previously, the same court denied Sandoz’s request for a temporary restraining order.  The FDA granted final approval to Teva and Ranbaxy on June 23, 2006, and the companies launched their products shortly thereafter.

    In today’s opinion, the district court wrote that Sandoz’s motion failed on each of the four factors:  likelihood of success on the merits, irreparable harm, balance of interests, and the public interest.

    Earlier this year, the FDA appealed a separate decision by the same district court that required the FDA to grant final approval to Teva and Ranbaxy upon expiration of Merck’s final orange book listed patent on Zocor.

    NOTE:  thanks to Kurt Karst for sending us a copy of today’s opinion.

  • Apotex Accuses Cephalon and Four Generic Drug Companies of Monopolizing the U.S. Market for Provigil

    Generic drug-maker Apotex filed a complaint on June 26, 2006 in the U.S. District Court for the Eastern District of Pennsylvania accusing Cephalon Inc. and its licensees, generic drug-makers Barr Laboratories, Mylan Laboratories, Teva Pharmaceuticals, and Ranbaxy Laboratories, with monopolization under the Clayton Act and the Sherman Act, and intent to monopolize under the Sherman Act.  The claims are based on patent infringement reverse payment settlement agreements between the parties under which none of the four generic licensees will commercialize a Provigil generic before April 2012.

    Cephalon markets Provigil (modafinil) for treating narcolepsy, and listed U.S Patent Nos. 4,927,855 (expires May 22, 2007) and RE 37,516 (expires October 6, 2014) in the Orange Book for Provigil. According to the Apotex complaint, exclusivity for Provigil as a new chemical entity expired December 24, 2003.  Each of Cephalon's generic licensees filed ANDAs on December 24, 2002 containing a Paragraph IV certification with respect to RE 37,516.  As a result, each of the four will share the 180 day marketing exclusivity for generic Provigil

    Cephalon filed suit in the U.S. District Court for the District of New Jersey on March 28, 2003, charging each of the generic licensees with infringement of RE 37,516.  The 30 month automatic stay against marketing of a Provigil generic expired September 28, 2005.  Cephalon subsequently received Orphan Drug exclusivity for Provigil, which extended until December 25, 2005.  Apotex later filed its ANDA for generic Provigil, meaning that it could not enter the market until after the 180 day exclusivity period lapsed.

    Apotex asserted in its complaint that, during discovery, Cephalon's generic licensees concluded that RE 37,516 had been obtained through inequitable conduct.  Apotex further asserted that Barr, Mylan, Teva, and Ranbaxy each had received tentative approval for their generic versions of Provigil prior to December 24, 2005 and that, in fear of imminent market entry by the generics based on their conclusion that RE 37,516 was invalid due to inequitable conduct (among other reasons), Cephalon entered into the disputed settlement agreements with each of the parties. Apotex thus based its monopolization arguments, at least in part, on assertions of: (a) fraudulent conduct by Cephalon in obtaining RE 37,516; (b) patent misuse in listing RE 37,516 in the Orange Book (or in not delisting it after settlement of the litigation); and (c) anti-competitive reverse payment agreements with Barr, Mylan, Teva, and Ranbaxy that keep generic Provigil off the market through until 2012, when in the absence of such agreements generic Provigil would have entered the market in late 2005 or early 2006.

    Apotex argued that this delay in generic entry, and the resulting delay in triggering of the 180 day exclusivity, caused it specific harm in not being able to market its own generic Provigil, and also caused harm to consumers by keeping the price of Provigil artificially high.

    Cephalon has also been sued for alleged antitrust violations arising out of the same settlement agreements in multiple class actions.  On June 30, 2006, the Pennsylvania Employees Benefit Trust Fund (PEBTF) filed a nationwide class action suit against Cephalon on behalf of end-payors.

    In addition to the Apotex and PEBTF suits, at east eight other suits have been filed against Cephalon in the U.S. District Court for the Eastern District of Pennsylvania relating to the Provigil settlement agreements.

  • Fourth Circuit Reaffirms Legality of Authorized Generics

    The Court of Appeals for the Fourth Circuit today affirmed a district court decision dismissing a lawsuit brought by Mylan Pharmaceuticals against the FDA, in which Mylan asserted that the FDA did not have the authority to approve an authorized generic of Proctor & Gamble’s Macrobid (nitrofurantoin).  The decision is consistent with Teva v. Crawford, which was decided last year by the Court of Appeals for the D.C. Circuit.

    In the case decided today, Mylan held rights to the 180 day exclusivity period for marketing generic nitrofurantoin, a drug used to treat urinary tract infections, with annual sales of $80 million.  A third party licensed by Procter & Gamble launched an authorized generic just as Mylan began marketing its own generic version of Macrobid.

    In the opinion, written by Judge M. Blane Michael for a unanimous panel, the court first observed:

    Mylan concedes that the language of section 355 (j)(5)(B)(iv) is plain.  The provision makes no mention of drugs under approved NDAs.  It speaks only about the rights of the paragraph IV ANDA applicant who files first as against all subsequent paragraph IV ANDA applicants.

    The court thus held that it was not arbitrary or capricious for the FDA to allow marketing of authorized generic drugs, and therefore the district court correctly dismissed the case for failure to state a claim upon which relief can be granted.  The Fourth Circuit concluded:

    Although the introduction of an authorized generic may reduce the economic benefit of the 180 days of exclusivity awarded to the first paragraph IV ANDA applicant, section 355(j)(5)(B)(iv) gives no legal basis for the FDA to prohibit the encroachment of authorized generics on that exclusivity.

  • Pfizer Subsidiary to Launch Authorized Generic Zoloft

    Pfizer announced that its subsidiary, Greenstone Ltd., will begin marketing an authorized generic version of Pfizer's anti-depressant Zoloft as soon as Teva introduces its generic version, which could happen as early as today.  As reported by Reuters, Teva's share price fell 3.9% on the news.  Teva, through its acquisition of Ivax, received 180 days of marketing exclusivity for generic Zoloft.

    The Boston Globe reported that Teva took the news of Pfizer's plans in stride.  According to a spokesperson for Teva, "The use of authorized generics by branded drug makers has been a common practice for years . . . .  Teva always expects to compete against an authorized generic whenever it launches a product within 180 days of exclusivity."

    A much different tone regarding authorized generics was sounded by the Generic Pharmaceutical Association (GPhA).  In response to a report released by the Pharmaceutical Research and Manufacturers of America (PhRMA) concluding that authorized generics can lead to lower drug prices, GPhA issued a press release in which it urged Congress to prevent the introduction of authorized generics during the 180 day exclusivity period.  GPhA asserted that authorized generics have appeared only in the last few years, and they represent "an anti-competitive response designed to deter generic companies from pursuing patent challenges by significantly diminishing the potential incentives" embodied in the 180 day exclusivity period.

    The difference in tone could reflect the fact that individual generic companies currently have options for selling generic drugs during the 180 day exclusivity period: (a) trying to obtain the 180 day period of exclusivity under Hatch-Waxman, or (b) negotiating with brand drug companies to become authorized generic distributors during the 180 exclusivity period.  The GPhA proposal would eliminate the second option, and may not be embraced by all GPhA member generic companies.