Actos, known generically as pioglitazone, is a medication used to treat patients with Type 2 diabetes. Takeda Pharmaceutical and Eli Lilly gained approval to sell the drug in the United States in 1999, although the drug is now solely manufactured by Takeda in the US. Actos is part of the thiazolidinedione drug class, which also includes the medication Avandia (rosiglitazone). Actos gained more popularity when Avandia was linked to heart attacks, but research linking it to bladder cancer has sparked safety concerns as well as thousands of lawsuits.
There is an ever-growing body of research showing that Actos is associated with an increased risk of bladder cancer. In fact, the drug was suspended in France and Germany at the request of those countries regulators because of its cancer risks. The U.S. Food and Drug Administration (FDA) has also addressed the potential dangers of Actos by updating its safety label to warn that it may increase the risk of bladder cancer after only one year of use.
Amidst mounting safety concerns, thousands of Actos lawsuits have been filed around the country. Some have been filed in state court but most have been filed in federal court as part of the multidistrict litigation entitled In Re: Actos (Pioglitazone) Products Liability Litigation. The MDL is centralized to the U.S. District Court for the Western District of Louisiana. Jerrold S. Parker, founding partner of Parker Waichman LLP, serves on the Plaintiffs’ Steering Committee in the litigation.
See below for a comprehensive timeline that includes the history of Actos, dates of label changes and updates on lawsuits and potential settlements.
Actos Timeline: Side Effects, Liability, Warnings, and Litigations
1781: 32-year-old Chobei Takeda started a business selling traditional Japanese and Chinese medicines in Doshomachi, Osaka.
1871: Takeda began transacting with foreign trading companies and purchasing Western medicines.
1895: Takeda acquired Uchibayashi Drug Works to establish its own factory in Osaka and became a pharmaceutical manufacturer.
1914: Research activities began with the establishment of a research division. Takeda expanded its pharmaceutical business and began exports to the U.S., Russia and China.
1925: The Company was incorporated as Chobei Takeda & Co., Ltd. The Company changed its name to Takeda Pharmaceutical Industries Limited in 1943.
1980: Upjohn Company, a pharmaceutical manufacturer and seller, signs a research agreement with Japan’s Takeda Pharmaceutical Co. Ltd. on pioglitazone, a drug class that is specifically used to target diabetes.
1993: Upjohn Company ended their research agreement with Japan’s Takeda Pharmaceutical Co. Ltd. According to a court documents, the collaboration ended due to Upjohn Management concerns about litigation over Actos and “concerns about some of the results from longer term toxicity studies on pioglitazone.”
1997: Takeda America Research & Development Center Inc. was established in the U.S. and Takeda American Holdings, Inc., a holding company for Takeda’s U.S. pharmaceutical business, was established
Jul. 1999: The U.S. Food and Drug Administration (FDA) approves Actos to treat patients diagnosed with type 2 diabetes mellitus. Takeda and Eli Lilly enter into a joint marketing agreement for Actos. 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
2003: Takeda Global Research & Development Center, Inc. is established in the U.S.
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, this information was not included in the original published study. It wasn’t published until 2009 and more clearly, in October 2011 in The Lancet.
Apr. 20, 2006: Takeda and Eli Lilly end their joint marketing agreement for Actos in the United States. Eli Lilly retained the marketing rights to sell Actos in parts of Asia and Europe, as well as Canada and Mexico.
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 worldwide in 2008 ($3.4 billion in 2009).
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.” This Whistleblower complaint was filed in the United States District Court, Court of Massachussets.
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. 1, 2011: Whistleblower, Dr. Helen Ge, files an additional whistleblower complaint in the United States District Court, District of Massachussets.
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.
April 22, 2011:The American Diabetes Association (ADA) published report, “Assessing the Association of Pioglitazone Use and Bladder Cancer Through Drug Adverse Event Reporting”. It was an analysis of the association of the use of Actos and bladder cancer. The ADA analyzed the U.S. Food and Drug Administration’s (FDA) Adverse Event Reporting System (AERS) between 2004 and 2009 and analyzed by the reporting odds ratio (ROR). The analysis showed an association of the reports involving bladder cancer with Actos.
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 (marketed as Actos, Actoplus Met, and Duetact) previously announced on June 15, 2011.
Sept. 30, 2011: Whistleblower Dr. Helen Ge files a first amended Whistleblower complaint in the United States District Court, District of Massachussets.
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. 5, 2012: Whistleblower Dr. Helen Ge files a first amended Whistleblower complaint in the United States Court, District of Massachussets.
Apr. 16, 2012: Health Canada updates label on Actos, warning about the potential risk of bladder cancer.
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.
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.
Jan. 28, 2013: Diabetic Medicine publishes a study showing that Actos is associated with an increased risk of bladder cancer. Researchers conducted a meta-analysis by looking at data from six different studies and 215,142 patients taking Actos. The median follow-up period was 44 months. Overall, the researchers found that “The hazard of developing bladder cancer was significantly higher in patients using pioglitazone”, with a hazard ratio of 1.23 compared to control groups.
Feb. 19, 2013: The first Actos trial begins in Los Angeles in Cooper v. Takeda Pharmaceuticals America Inc., CGC-12-518535, California Superior Court (Los Angeles). Plaintiff Jack Cooper was diagnosed with bladder cancer after taking Actos for more than four years. His lawsuit is one of thousands alleging that the diabetes drug caused cancer and also alleges that Takeda failed to warn about these risks.
Apr. 26, 2012:
Takeda Pharmaceuticals U.SA. announces that the first Actos trial concluded with a Los Angeles jury awarding $6.5 million to the plaintiff, Jack Cooper. The case was Jack Cooper et al. v. Takeda Pharmaceuticals America Inc., et al. (Cooper v. Takeda Pharmaceuticals America Inc., CGC-12-518535, California Superior Court Los Angeles). The trial was held in Los Angeles before Judge Kenneth R. Freeman.
January 27, 2014: First Federal Actos Bladder Cancer bellwether trial begins In Re: Actos (Pioglitazone) Products Liability Litigation (MDL No. 2299); the federal litigation is taking place in the U.S. District Court for the Western District of Louisiana, with the Honorable Rebecca F. Doherty, presiding. The plaintiffs are Terrence Allen and his wife, Susan. Mr. Allen alleges he developed bladder cancer after taking Actos from 2004 until 2011 and that Takeda hid these risks from consumers.