FDA relaxes guidelines for abortion-inducing drug, flames abortion controversy

The FDA announced a labeling change for the drug Mifeprex®, which, when used together with another drug called misoprostol, will terminate a pregnancy in the early stages. The labeling change will relax certain guidelines in prescribing practices and expand the time in which women can take this drug in order to induce an abortion. This change comes at a controversial time as the Supreme Court just heard oral arguments, and oddly asked parties for additional briefing, in a challenge to the contraception mandate under the Patient Protection and Affordable Care Act (ACA) (P.L. 111-148). At the same time, anti-abortion candidates in the race to the White House have recently fueled the fire with inflammatory remarks while some pro-life proponents are framing the FDA’s change as a political move.

Labeling changes

While the FDA first approved Mifeprex in 2000, the latest announcement outlines a new approved regimen which was found to be safe and effective after a supplement application was submitted by the manufacturer. The FDA stated that the drug may be appropriately used to end a pregnancy through 70 days of gestation and through the following procedure:

  • The ingestion of 200g of Mifeprex on day one;
  • The ingestion of 800mcg of misoprostol 24 to 48 hours after taking the Mifeprex; and
  • A follow-up with a health care provider seven to 14 days after taking the Mifeprex.

The FDA also outlined an appropriate risk evaluation and mitigation strategy (REMS) for Mifeprex, as follows: (1) that it must be ordered, prescribed, and dispensed under the supervision of a health care provider with certain qualifications; (2) that those health care providers must complete a Prescriber Agreement Form before prescribing; (3) that it only may be dispensed in clinics, medical offices, and hospitals; and (4) the provider must obtain a Patient Agreement Form before dispensing it.

Effect

Other than extending the time in which this medication can be prescribed from seven weeks to 10 weeks, the new labeling reflects a change in dosage and procedure that, according to some sources, was adopted by physicians that prescribed Mifeprex off-label long ago. “The change brings the direction for taking the drug . . . in line with what has become standard medical practice in most states: reducing the dosage to 200 milligrams from 600 milligrams, decreasing the number of visits a woman must make to the doctor to two from three, and extending the period when she can take the pill to 10 weeks of pregnancy from seven weeks,” according to the New York Times. There is also evidence that fewer side effects accompany the lower dosage. The same article notes that while the new labeling might be applicable to all states at the moment, at least one state is already working to pass a law that would hold provider’s to the stricter standards imposed in the past.

Context

This FDA approval came at an interesting time for the abortion and contraceptive coverage controversy as, the day before this announcement, the Supreme Court issued an order asking for supplemental briefing in a case on which it had heard oral arguments the previous week and which challenged the contraception coverage mandate of the ACA. Some experts see this as the eight-Justice Court potentially looking for an avenue to strike a compromise on an issue and avoid a 4-4 vote, which would effectively result in the continuation of a circuit split and different laws applying in different jurisdictions on this issue. In this context, pro-life proponents argued that the FDA announcement is a politically fueled move to satisfy the “abortion industry” and pro-choice groups. Others defended it as unrelated to election year politics and as simply part of the FDA’s regulatory responsibility in the face of a supplement drug application.

TPP: years in the making, years to go

The Trans-Pacific Partnership (TPP) was signed by the trade ministers of 12 nations on February 4, 2016, in New Zealand, and thus, the world’s largest trade deal is now waiting for ratification of the treaty’s text in each nation. Here in the United States, President Obama has called upon Congress to vote on and pass the TPP before he leaves office in early 2017. In 2009, the U.S. began negotiating the TPP, seeking to boost U.S. economic growth with Canada, Mexico, and several Asian and Pacific countries considered key destinations for U.S. manufactured goods, agricultural products, and services suppliers. As a group, the TPP countries are the largest goods and services export market of the U.S., accounting for $698 billion in 2013, or 44 percent of total U.S. goods exports. U.S. exports of agricultural products to TPP countries totaled $58.8 billion in 2013, 85 percent of total U.S. agricultural exports. The TPP seeks to slash tariffs and trade barriers in this region, but pointedly does not include China.

At the core of the debate over the TPP, concerns have been raised about its application and impact on countries’ regulations—in particular the TPP’s key feature of regulatory coherence for the promotion of trade. For the pharmaceutical industry, issues concerning intellectual property (IP) protection in the TPP have focused primarily on patents, but there are concerns that the patent protection schema is not as effective for some classes of drugs such as biosimilars because these products do not require exact identity with the reference product. The Patient Protection and Affordable Care Act (ACA) (P.L. 111-148) established a pathway for biologics that employs a 12-year exclusivity period, which is in stark contrast to the five years for generic small-molecule drugs.

A difficult question to answer is whether an inventor of a new drug measures the cost of invention against the revenue that might be made in the “poor” world in calculating whether to undertake the research and development of the drug. Supporters of the TPP argue that the greater cost and difficulties involved in research and development of biologics required a longer exclusivity period as incentive for innovation. Critics look at the TPP as an attempt to use trade law and treaties to extend the “rich” world IP protections to the “poor” world.

In addition, there is strong opposition from many congressional Democrats and some Republicans, which could mean a vote on the TPP is unlikely before President Obama leaves office. These concerns and a myriad of others will still require years of tough negotiations before the TPP becomes a reality.

CBO Says Bill Targeting ‘Pay-For-Delay’ Agreements on Generics Could Save Taxpayers Billions

Senator Charles Grassley (R-IA) and Senator Herb Kohl (D-WI) announced November 8, 2011, that the Congressional Budget Office (CBO) had scored their bill to ban pay-for-delay agreements (S. 27) as saving the federal government $4.8 billion over ten years. Citing the cost savings, the Senators called for the Joint Select Committee on Deficit Reduction to include the proposal as part of any final deficit reduction package.

CBO anticipates that enacting the Preserve Access to Affordable Generic Drugs Act (S. 27) would accelerate the availability of lower-priced generic drugs and generate $4.785 billion in budget savings between fiscal years 2012 and 2021. CBO also estimates that earlier entry of generic drugs affected by the bill would reduce total drug expenditures in the U.S. by roughly $11 billion over the decade.

The bill would deter “pay-for-delay” settlements in which brand name drug companies settle patent disputes by paying generic drug manufacturers in exchange for the promise of delaying the release of the generic version into the market. Under the legislation, these agreements would be presumed illegal and the Federal Trade Commission (FTC) would be provided heightened authority to scrutinize the agreements.

Last month, Kohl and Grassley sent a letter urging the Joint Select Committee on Deficit Reduction to include the bill as part of its budget-cutting effort. “In these settlements, brand name pharmaceutical companies pay millions of dollars in cash or other valuable consideration to generic drug companies to settle drug patent litigation, in return for the generic drug company agreeing to withhold marketing its generic drug until the end, or shortly before, the expiration of the patent.”

“These pay for delay settlements deprive consumers of years of generic drug competition, while enriching both the generic drug company and the brand name manufacturer, which maintains a monopoly on the drug. However, consumers lose by paying substantially higher prices and the government loses by paying substantially higher drug reimbursement payments under Medicare and other federal health programs,” the senators said in the letter.

In the late 1990s, the FTC challenged several pay-for-delay agreements as being anti-competitive and shortly thereafter, the use of agreements declined, according to Kohl. From 2000-2004, patent cases continued to settle, but the settlements did not include payments to generic drug manufacturers.

Since 2005, three Circuit Courts of Appeals decisions have rejected these antitrust challenges, and held that the rights of patent holders make virtually any patent settlement permissible, even anti-competitive settlements, “trumping antitrust law.” These precedents have made it very difficult for the FTC to successfully challenge these pay-for-delay settlements. “Our legislation would ensure that these anticompetitive pay-for-delay agreements are properly subject to antitrust scrutiny,” Kohl said.

Last month, the FTC released a staff report that found that drug companies entered into 28 potential pay-for-delay agreements in FY 2011, nearly matching the previous fiscal year’s record of 31 deals. Overall, the agreements reached in the latest fiscal year involved 25 different brand-name pharmaceutical products with combined annual U.S. sales of more than $9 billion, according to the FTC. In a statement, FTC Chairman Jon Leibowitz also called on the supercommittee to ban pay-to-delay agreements.

The agency has had difficulty persuading courts that pay for delay is illegal. In March, the U.S. Supreme Court let stand a decision from the U.S. Court of Appeals for the Second Circuit that found a pay for delay deal between Bayer AG and Barr Pharmaceuticals (now owned by Teva Pharmaceuticals) to drop a patent lawsuit over the antibiotic Cipro did not violate antitrust laws. The FTC also lost a case in the 11th Circuit challenging a pay for delay deal between Schering-Plough Corp., Upsher-Smith Laboratories and American Home Products Corp. involving the high blood pressure medication K-Dur 20.
In July, the Senate Judiciary Committee favorably reported the bill (S. 27). The Obama Administration actively lobbied in favor of the measure, and President Obama included a similar provision in his 2012 budget outline.

During consideration of the bill, Senator Kohl said the legislation is needed to “prevent one of the most egregious tactics used to keep generic drugs off the market.” Voting against the bill, Senator Orrin Hatch (R-UT) told the committee that S. 27 would create a “high burden of proof” that would “deter patent challenges in the future” and “give unprecedented authority to unelected Washington bureaucrats.” Although Hatch said he understood the desire to “curtail abuses,” S. 27 would create “expensive delays,” “discourage innovation,” and hurt the very people it was intended to help.

The Generic Pharmaceutical Association opposes the legislation. In a September 21, 2011 letter to the super committee, the GPhA said that patent challenges and settlements actually accelerate the introduction of competition into the pharmaceutical market. “Banning patent settlements is anti-consumer because these settlements guarantee early market entry,” the group said. Only a small number patent challenges have involved litigation settlements between the brand and generic companies. “While it seems counterintuitive, the fact is that patent settlements have…brought more affordable products to market sooner than otherwise would have been possible,” the GPhA said in a statement.

The association pointed out that the FTC and the Department of Justice already have the authority to review and reject any patent settlement. The Pharmaceutical Research and Manufacturers of America agrees. PhRMA President John Castellani has said that restricting such settlements, “which already are subject to review by the Federal Trade Commission and the Department of Justice” could “keep generics from being available to patients for years.”

Still No “Sunshine” – in the Name of Lighter Regulatory Burdens

Centers for Medicare and Medicaid Services (CMS) Administrator Don Berwick said on October 31 that the agency would delay further rules implementing a provision in the health reform law that requires drugmakers and device companies to report all payments and gifts to physicians.

The Physician Payment Sunshine Act was included in the health care reform law enacted last year (Patient Protection and Affordable Care Act, P.L. 111-148), as a way to reduce healthcare costs through greater transparency. PPACA requires pharmaceutical, medical device, biological, and medical supply manufacturers to track and report to the CMS all payments to doctors above $10. Non-compliance may result in fines of up to $10,000 for inadvertent non-compliance and up to $100,000 for knowing non-compliance. The first reports will be due March 31, 2013 for the calendar year 2012 reporting period which begins in three short months.

The effort is meant to “shine light” on the industry’s gifts to physicians, which critics maintain can improperly influence patient care and treatment decisions, as explained here.

CMS missed the statutory October 1 deadline for publishing the regulations that would clarify certain definitions and provide detailed instructions on how these reports are to be compiled and submitted, but not because the rules are controversial – which they are – but because the agency is trying to lighten the burden of red tape.

In an October 28, 2011 letter to Senators Herb Kohl (D-WI) and Charles Grassley (R-IO), Berwick cited a presidential order from last January that calls on federal agencies to minimize regulatory burdens. “I believe we can implement the statutory goals of (the Sunshine Act) while minimizing burden on the regulated parties. In that vein, CMS is carefully reviewing this statutory requirement and working hard to ensure we meet these goals.”

[Earlier this year, President Obama instructed federal healthcare agencies to streamline regulations that impede flexibility, unnecessarily burden resources, reduce efficiency, increase costs and decrease quality of care. In that vein, CMS recently released three new rules intended to remove or revise outdated, duplicative, overly burdensome and unnecessary regulations, thereby saving the healthcare system an expected $1.1 billion per year and more than $5 billion over five years. Whether the expected savings and efficiencies called for by the Obama administration will actually be achieved through these new rules remains to be seen.]

In his letter to Senators Kohl and Grassley on the Sunshine Act rules, Berwick gives no explanation for the delay and no indication of when CMS may actually issue the guidelines. The irony, of course, is that this is the same administration that wanted to enact the Sunshine provision in the first place.

On November 1, Senator Grassley responded in a statement, “The administrator’s response doesn’t tell us anything new. There’s no explanation for the delay and no indication of when to expect completion. It’s an inadequate response any way you look at it.”

The Pharmaceutical Research and Manufacturers of America (PhRMA) and other groups have advanced a proposal that the initial reporting period, scheduled to begin January 1, 2012, should be delayed for the same amount of time that the rule is; e.g., if the rule is 6 months late, the first reporting period would not be January 1- December 31, 2012 but July 1- December 31, 2012; they would leave in place the requirement that the first actual report from pharma and device companies to HHS would be due the 1st quarter of 2013, but would shorten the time period to be covered in that first report. CMS has not commented on the PhRMA request.

The PhRMA proposal sounds only fair. After all, the longer CMS waits to publish the rules, the more time companies will need to comply, i.e., “minimizing [the] burden.”