FDA opens portal to future science and tech trends

The FDA is lending additional support behind “horizon scanning,” a practice in which government and business entities collaborate to gather information broadly about emerging trends in science and technology. Horizon scanning helps these entities develop better capabilities to react to the quickly changing field. The FDA set up its own intra-agency horizon scanning group back in April 2015 – the Emerging Sciences Working Group – comprised of representatives from various FDA product and research centers.

Along those lines, the FDA is asking science and technology experts in the private sector to submit predictions on the next “new” items in their field of specialization. The agency stressed that it is not looking for advances already under discussion, but instead is seeking information about scientific and technological advances under the radar–so far under that a web search would have difficultly finding it. The FDA’s ability to achieve its stated agency mission relies on awareness of, and proactive preparedness for, emerging issues and scientific advances, which will impact the development of regulated products well in advance of formal FDA regulatory submissions, which can be anywhere from five to 10 years prior to when the regulatory submissions arrive at the FDA.

The information should be submitted electronically to the FDA’s Emerging Sciences Idea Portal. The portal is public, so confidential information should only be provided in writing. The FDA makes no promises on response, but did note that it would ask for more information if the submission sufficiently interested the agency. The FDA will use this information gathering to assist in the agency’s science-based planning, programs, policies, reporting, and communication within and outside the FDA. The public docket will be available for comment submissions through October 2019.

Supreme Court lets patent invalidation stand, generic Cubicin® could be coming

The U.S. Supreme Court will not hear a brand-name antibiotic manufacturer’s appeal of a decision invalidating its patents, meaning that a competitor can proceed with its plans to manufacture a generic version of the drug. A federal district court determined that four patents for the injectable drug Cubicin® were invalid for obviousness. Cubist Pharmaceutical, Inc., later acquired by Merck & Co., Inc., appealed the decision to the Federal Circuit, which sided with the district court in November 2015 (Cubist Pharmaceuticals, Inc. v. Hospira, Inc., Fed. Cir., November 12, 2015). Cubist sought certiorari, arguing that the Federal Circuit’s rules on patents were too restrictive regarding obviousness. Hospira had opposed the petition because it would result in the High court conducting its own factual analysis on the validity of the patent. The High Court’s denial of certiorari means that Hospira, Inc., acquired by Pfizer, Inc. in 2015, may pursue authorization to sell a generic version of the daptomycin product.

Cubicin (daptomycin for injection) is an injectable antibacterial product used to treat complicated skin and structure infections (cSSSI) and staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis. Hospira filed an abbreviated new drug application (ANDA) with the FDA in 2011 to sell a daptomycin product equivalent to Cubicin before the expiration of the Cubist patents. Cubist filed suit pursuant to the Hatch-Waxman Act (P.L. 98-417) alleging that Hospira had infringed on its five patents. Although the court found Hospira infringed on one patent, it determined that the remaining four patents were invalid because they were based, in part, on less frequent administration of a drug, and the benefit of less frequent administration would have been obvious to a person of skill in the art.

The fifth patent expires in June 2016. Upon its expiration, Hospira can move forward with plans to sell a generic daptomycin product.

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.

Generic drug prices skyrocket, lack of alternatives lead to costly choices

Typically, providers and patients search for a generic equivalent of a drug to reduce costs. Yet generic drug prices are, in some cases, becoming cost prohibitive. Recently, the University of Utah Health Care system told US News it has removed a generic drug from its crash cart because of the price. Calls for investigation into the problem have been surfacing for years, and perhaps the public relations nightmare a company recently underwent after announcing a huge price hike will get the ball rolling.

High costs, higher stakes

Limiting access to these high cost drugs can lead to life-or-death decisions. Erin Fox, director of University of Utah’s drug information service, tracks drug shortages and found that isoproterenol hydrochloride (brand name Isuprel®) jumped to $2,700 a vial from its $50 price two years ago. Most of the network’s patients are covered by managed care plans, which do not pay enough to cover the $1.6 million needed to provide the drug. She notes that the hospital has managed even though critically ill heart patients would benefit from the drug, and that doctors still use it if a patient’s life is at stake.

Isuprel’s huge price hike caught the eye of the Heart Rhythm Society (HRS), which published a special notice in April 2015 about the price increase. The HRS noted that the price increase was due to changes in ownership. When Hospira owned the drug, the dosage price was $44.50. Marathon Pharmaceuticals bought the drug and increased the price to $218.30 per dose. In February 2015, Valeant Pharmaceuticals International, Inc. (Valeant) purchased the drug and increased the dosage to $1,200. Apparently, the price more than doubled by the time Fox was interviewed by US News. The HRS notice called for action, seeking help gathering information about Valeant’s price increase and advising members to collaborate with their local pharmacies in finding alternatives. It committed to working with the American Medical Association (AMA) to lobby for fair and accurate pricing.

Bad PR for drug companies

Although generic price hikes have been happening for some time, the media latched onto the story of Daraprim® several months ago. Turing Pharmaceuticals (Turing), a start-up company, acquired the rights to the drug, an antibiotic that treats a parasitic infection. The drug is many decades old, and cost $13.50 per tablet. Turing immediately jacked the price up to $750 a dose. This drug is vital for those who become infected with toxoplasmosis during pregnancy or for those with AIDS and certain cancers that suppress the body’s immune response. Martin Shkreli, Turing’s founder, said that the drug is rarely used and the company would use the money it collects to develop better toxoplasmosis treatments.

Despite Shkreli’s claims, the backlash was loud and fast. Some doctors stated that a new therapy option was not vital, and the switch from drugstores to controlled distribution made it harder for other companies to get enough samples to make their own copies. Like with Isuprel, some hospitals began questioning if it made fiscal sense to stock the drug, and others began reviewing every case. Express Scripts, a pharmacy benefit company, announced its decision to partner with Imprimis Pharmaceuticals to offer a compounded oral form of the primary ingredient in Diaprim for $1 per capsule. After the media hoopla, Shkreli decided to reduce Diaprim to a more affordable price.

Why generics?

Patients and insurers can breathe a sigh of relief when a drug patent runs out and the exclusivity period is exhausted, allowing new, cheaper generic options to flood the market. Pharmaceutical companies have long been known to do whatever they can to extend the life of their brand-name drugs. So why the price hike for generics? Forbes looked into the matter in February 2015, finding staggering numbers of generic drug use: nearly 80 percent of all prescriptions. These drugs are about 80 to 85 percent cheaper than brand name counterparts. In 2012 and 2013, $33 billion and $47.5 billions of sales value, respectively, lost their patents. Generics have saved the health care system over a trillion dollars since 2003, but 222 drug groups at least doubled in price between 2013 and 2014.

Forbes identified several sources of the problem. When the generic drug market was saturated in 2009, manufacturers began consolidating to achieve larger portions of the market. Fewer manufacturers producing each drug leads to less competition and less of an incentive to reduce prices. Then when one of these few manufacturers run low, rules of supply and demand cause the prices to rise. Some retailers have gone so far as to drop certain generics from their drug discount programs.