Over 700 commonly used generic medicines were recommended for suspension by the European Medicines Agency (EMA) based on data integrity concerns, over clinical studies conducted at GVK Biosciences in Hyderabad, India.What will be the global fallout of the European decision? The European decision has impacted products from companies such as:Abbott Laboratories, Accord Healthcare (Intas), Actavis, Alembic, Apotex, Betapharm (Dr. Reddy’s), Brown & Burk UK, Fair Med Healthcare AG, Glenmark, Lupin, Micro Labs, Mylan, Orion Corporation, Ranbaxy, Ratiopharm, Sandoz, Sanofi-Aventis, Stada, Teva, Torrent, Wockhardt, Zydus… and many, many more.The original recommendation of suspending some of the medicines made in January 2015, was an outcome of an inspection of GVK Biosciences’ site in Hyderabad (GVK BIO is a Clinical Research Organization- CRO) by the French medicines agency (ANSM) through the EMA. The EMA stated in their official release: “The inspection revealed data manipulations of electrocardiograms (ECGs) during the conduct of some studies of generic medicines, which appeared to have taken place over a period of at least five years. Their systematic nature, the extended period of time during which they took place and the number of members of staff involved cast doubt on the integrity of the conduct of trials at the site.” 1000 drugs reviewed// 700 rejectedWhile over 1,000 pharmaceutical forms and strengths were reviewed at the GVK site, over 300 of them had sufficient supporting data available from other sources. As a result, these medicines were allowed to remain on the market in the EU.However, for the over 700 other medicines, the EMA after its second review, maintained its previous recommendation of January 2015, to suspend medicines, where no additional supporting data from other studies was available. Only one exception after that second review was spared from suspension, as the company was able to address the EMA’s concerns: it was Bivolet Nebivolol (5 mg tablets/ marketing authorisation holder: Neo Balkanika EOOD).While the agency noted that “there is no evidence of harm or lack of effectiveness linked to the conduct of studies by GVK Biosciences at Hyderabad. Some of these medicines may remain on the market” if they are of critical importance for patients. However, the recommendation will now be sent to the European Commission for a legally binding decision, which will apply to Member States regardless of the decision taken in the interim period.The updated list of medicines for which, the CHMP (Committee for Medicinal Products for Human Use) recommends suspension, is available on the EMA website. Companies are given 12 months to submit additional data. The potential global impact of the European suspensions?The GVK Biosciences scandal is almost as severe in magnitude and impact, as the data falsification concerns, which were discovered at Ranbaxy (Katherine Eban’s stunning investigation in Fortune, “Dirty Medicine” covers this extensively). One of the main promoters of GVK Biosciences is Mr. D.S. Brar who was CEO & Managing Director of Ranbaxy from 1999-2004. The impact of GVK Biosciences’ misdeeds is already being felt on new product launches. Mylan recently withdrew its European application for generic Abilify (aripiprazole) (2014 sales US$6.2x billion) citing “identification of major GCP issues (Good Clinical Practices).” What about the impact on the US market?In 2010, FDA discovered data integrity violations, which bankrupted clinical research organization, Cetero Research/PRACS. Based on the Cetero findings in the United States, the EMA suspended seven drugs. Now it remains to be seen, how the FDA will handle the data integrity concerns found in Europe since products like repaglinide & candesartan cilexitil (Mylan), levetiracetam (Dr. Reddy’s), clonazepam (Sandoz), metformin hydrochloride (Actavis), tacrolimus (Panacea Biotech) all have U.S. FDA approvals. Leading GVK Biosciences’ defense is the Indian government, who warned last month that if the European Union does not reconsider their decision, it may go to the World Trade Organization. The Indian government’s position is based on an appeal by GVK Biosciences, which made the “Indian government set up a panel of experts last year to investigate the matter and found no manipulation”, GVK Biosciences CEO Manni Kantipudi told Reuters.However, globally reputed GMP expert, Lachman Consultants, believes that the GVK Bioscience episode “could potentially impact data integrity, similar to the Cetero/PRACS case”.It’s clear for us that this is not the end of the story…
Why do “Americans pay, by far, the highest prices in the world for prescription drugs”? This concern has reached an unprecedented level where government and non-government lawmakers are taking a very serious view of this problem. Hilary Clinton has already made it “a campaign priority” for her 2016 presidential election bid. * Valeant pharmaceuticals buys two heart drugs in February and increased their list prices by 525% and 212%. The reason, company was doing “our duty is to our shareholders and to maximize the value” * Study published in the journal Neurology on the cost of multiple sclerosis treatments, found drugs originally costing $8,000 to $11,000, now cost about $60,000 per year. The cost of increase is at rates 5 to 7 times higher than prescription drug inflation. Drug costs in the United States currently are 2 to 3 times higher than Canada, the U.K. and Australia. * The Wall Street Journal wrote about “lawmakers in a handful of states stretching from California to Massachusetts, have introduced bills in a bid to force the pharmaceutical industry” to disclose their costs. * In response to pressure by Senators Bernie Sanders and Elijah Cummings, the inspector general of Health & Human Services (HHS) will investigate how recent increases in generic drug prices, have impacted the Medicaid rebate program (for better understanding of the program and the reason why IMS data is different to company sales data, read this Forbes article . * Massachusetts Attorney General, Maura Healey demands why prices of naloxone, which is used to reverse heroin overdoses, has “skyrocketed ” since a public health emergency was declared a year ago. * The JAMA Oncology Study found that price of cancer drugs is independent of novelty and yet cancer drug prices have risen faster than prices in other sectors of health care. The pharmaceutical defense: * The historical response, of the pharmaceutical industry, for the reason behind high cost of drugs is that funds are needed to continuously research and develop novel medicines. * “The price charged for an individual drug is not a reflection of development costs,” says Ken Kaitin, director of the Tufts Center for the Study of Drug Development. * The Generic Pharmaceutical Association also states that “since 2008, the price of brand drugs has almost doubled, but the price of generic drugs has been cut roughly in half.” The counter argument: In an interview , Dr. Steve Miller CMO at Express Scripts said, “The industry is still innovating, but on a financial model of drug development that has little to do with science. The acquisition of Pharmasset by Gilead Sciences solely to obtain the rights to the HCV blockbuster Sovaldi is a good example. The drug was already through Phase III trials and Pharmasset had determined $36,000 per treatment was the right price; then Gilead bought the company, for $11 billion, and promptly added $50,000 to the asking price for Sovaldi. That’s not what is meant in recognizing an “innovative step.” Pharmaceutical giant Actavis CEO, Brenton Saunders “growth pharma” model, which believes “the idea that to play in the big leagues you have to do drug discovery is really a fallacy” will not help win public sympathy. When assessing the price increase of generic drugs, the United State Senators mentioned that the prices of “certain dosages or dose forms of a product have increased rapidly while prices for other doses remained flat or declined”. An example given is Fluconazole 100mg tablet having experienced a price increase of 954%, while the 150mg actually had a price decline of 8%. The reality: Consistent with the conclusion in the JAMA Oncology study “that current pricing models are not rational, but simply reflect what the market will bear". Expected action: HHS conducted an investigation on generic drug price increases in 2007 and recommended that generic drug makers pay rebates to state Medicaid programs. The practice is currently standard for branded pharmaceuticals. Although lawmakers are pushing this course of action, the inaction since 2007 and study on multiple sclerosis drugs shows limited benefit if generic drugs are made to pay rebates. A far more likely outcome will be a European model, where federal health care programs like Medicare and Medicaid negotiate directly with drug makers to get lower prices. This provision was added in the recent budget of President Obama, but currently there is no progress. While regulators create their legislation, the pharmaceutical industry is in serious consolidation mode. If the Teva, Mylan deal comes through, and they combine, the options of negotiating with generic companies are going to seriously reduce.