Timeline: Actos (pioglitazone)


actos timelineJul. 15, 1999: The U.S. Food and Drug Administration (FDA) approves Actos to treat patients diagnosed with type 2 diabetes mellitus. The drug is launched by manufacturers Takeda Pharmaceutical and Eli Lilly & Co.

Oct. 13, 2000: The European Medicines Agency (EMA) approves Actos to treat type 2 diabetes mellitus

Oct. 8, 2005 – Results of the Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events) demonstrated a higher percentage of bladder cancer cases associated with Actos use than competitors’ drugs.  However, researchers decided that the bladder cancer could likely be attributed to other causes, and did not publish the information in the original study.

2006-2009: As part of a government funded study, data is collected from diabetic patients taking Actos in France.

Aug. 14, 2007: FDA releases a safety alert concerning Actos and other similar drugs, to include a new “boxed” warning on their labels. The agency stated that the alert was meant to emphasize that pioglitazone may cause or exacerbate heart failure, particularly in certain patient populations.” The blackbox warning was addressed to Takeda and GlaxoSmithKline, who manufactures Avandia

2008 – Actos becomes the 10th most-prescribed drug in the United States. Worldwide sales reach $4.6 billion.

Mar. 24, 2009– The Ministry of Health, Labour and Welfare in Japan approves Actos for concomitant therapy with insulin in patients with type 2 diabetes.

Apr. 2009: Takeda buys back the rights to Actos from Eli Lilly in seven countries including Canada, Sweden and Norway. In explaining the motive behind this strategic move, Takeda said it was an effort to increase “the enhancement of our presence in each region of the world to further establish Takeda as a world-class pharmaceutical company.” cites FiercePharma

Jan-Oct 2010: At outpatient retail pharmacies, an estimated 2.3 million patients fill a prescription for Actos or medication containing Actos, according to the FDA.

Jan. 18, 2010 – Takeda Pharmaceutical Company Limited (“Takeda”) announces approval from the Japanese Ministry of Health, Labour and Welfare to market Actos® OD (orally disintegrating) tablets for the treatment of type 2 diabetes.

Jun. 2010: A Whistleblower suit is filed against Takeda Pharmaceutical Co. Under the False Claims Act, former medical reviewer Helen Ge, files a suit on the government’s behalf alleging that cases of congestive heart failure “were not properly identified or reported in the FDA’s safety database,”

Aug. 24, 2010: The Circulation: Cardiovascular Quality and Outcome Journal publishes a study that demonstrates a similar risk of heart attack and acute heart failure in both Actos and Avandia; previously, Avandia was considered more dangerous because of its effects on cardiovascular health.

Sept. 17, 2010: The FDA is conducting an ongoing safety review concerning the increased risk of bladder cancer associated with exposure to Actos. The agency states that it is analyzing data from an ongoing ten-year study looking at the relationship between the drug and bladder cancer. Although some findings in animal and human studies suggest a possible connection, the FDA does not make any definitive statement about the link between Actos and bladder cancer.

Jan. 2011: Takeda’s patent on Actos expires. However, Takeda has a deal with generic drugmakers Ranbaxy of India and U.S. based Watson Pharmaceuticals and Mylan to delay the release of the generic until August 2012.

Mar. 16, 2011: By request of the European Commission, the EMA’s Committee for Medicinal Products for Human Use CHMP starts a review of Actos, Glustin, Competact, Glubraca and Tandemact to analyze the use of these medications related to the risk of bladder cancer.

Jun. 9, 2011: The EMA issues a press release concerning findings from the French Medicines Agency, and its decision to suspend Actos from the market. The EMA does not make any definitive claims at this point, but states that ongoing reviews will continue.

Jun 10, 2011: Use of Actos is banned in France and Germany. The French Medicines Agency removed the drug from the market after analyzing the data collected from 2006 to 2009.

Jun. 15, 2011: FDA announces “that use of the diabetes medication Actos (pioglitazone) for more than one year may be associated with an increased risk of bladder cancer.” Warning labels are to be updated subsequently. The agency warns healthcare professionals against prescribing Actos in patients who have bladder cancer or have a history of bladder cancer.

Jul. 2011: The EMA states that Actos should include the risk of bladder cancer on its warning label, according to Reuters.

Aug, 4, 2011– The FDA approves the label change for product containing pioglitazone, previously announced on June 15, 2011.

Dec. 2011: Takeda may face over 10,000 lawsuits, according Bloomberg Businessweek

Mar 12, 2012: Jerrold Parker, co-founder of Parker Waichman LLP, is named to the Plantiffs’ Steering Committee, in the multidistrict litigation (MDL) No. 2299.

Apr. 16, 2012: Health Canada updates label on Actos, warning about the potential risk of bladder cancer.

Apr. 27, 2012: Parker Waichman LLP files a lawsuit on behalf of a West Virginia man who allegedly developed bladder cancer as a result of long-term Actos use.

May 31, 2012: A study published in the British Medical Journal (BMJ) finds that the risk of bladder cancer is doubled in patients who take Actos for at least two years and have a cumulative dose greater than 28,000 mg.

Jun. 11, 2012: The Archives of Internal Medicine publishes a study linking thiazolidinedones, specifically Actos and Avandia, to diabetic macular edema, a condition that causes swelling in the eye. Researchers found a macular edema in 1.3 percent of Actos and Avandia users versus 0.2 percent among non-users.

Jun. 14, 2012: Parker Waichman LLP files a lawsuit on behalf of 10 plaintiffs who took Actos and developed bladder cancer, alleging that the diabetes drug caused the cancer and other subsequent complications. The suit was filed in the U.S. District Court for the Western District of Louisiana to be centralized in the Actos multidistrict litigation.

Jun. 15, 2012: Parker Waichman LLP files a wrongful death lawsuit on behalf of the estates of a Louisiana man and a Kentucky man; both men developed bladder cancer and died after taking the drug. The complaint was filed on June 15th in the U.S. District Court for the Western District of Louisiana, where it is one of many cases pending in the Actos multidistrict litigation. Takeda Pharmaceuticals America, Inc., Takeda Pharmaceuticals USA, Inc., Takeda Pharmaceuticals North America, Inc., Takeda Pharmaceutical Company Limited and Eli Lilly and Co. are named as Defendants.

Jul. 3, 2012: The Canadian Medical Association Journal (CMAJ) published a meta-analysis looking at thiazolidinediones and bladder cancer that incorporates 10 studies and over 2.6 million patients. Overall, researched found that Actos was linked to an overall increased risk of 22 percent.

Jul. 13, 2012: A court order sets the first federal Actos bladder cancer trial for November 3, 2014, and the second trial for July 8, 2015. The cases are part of the Actos multidistrict litigation as part of the In re: Actos (Pioglitazone) Products Liability Litigation.

Aug. 9, 2012: The Journal of the National Cancer Institute publishes a study suggesting an increasing risk of bladder cancer when using Actos and other TZDs for more than five years.

Aug. 17, 2012: The FDA approves generic versions of Actos. The drug is to be manufactured by Mylan Pharmaceuticals in 15 mg, 30 mg and 45 mg doses.