FDA Warns Merck & Co., AstraZeneca PLC and Boehringer Ingelheim About Joint Pain With Diabetes Drugs
Published: Sep 02, 2015
September 1, 2015
By Mark Terry, BioSpace.com Breaking News Staff
The U.S. Food and Drug Administration (FDA) published a warning on Friday for several type 2 diabetes medication in a drug class dipeptidyl peptidase-4 (DPP-4) inhibitors. The specific drugs are sitagliptin, saxagliptin, linagliptin and alogliptin.
Drugs included in this class include Merck & Co. ’s Januvia, AstraZeneca PLC ’s Onglyza, and Eli Lilly and Company /Boehringer Ingelheim’s Tradjenta, and others.
The warning indicated patients should not stop taking the drug, but should discuss any severe and persistent joint pain with their physicians. “In a search of the FDA Adverse Event Reporting System (FAERS) database and the medical literature, we identified several cases of severe joint pain associated with the use of DPP-4 inhibitors. Patients started having symptoms from 1 day to years after they started taking a DPP-4 inhibitor. After the patients discontinued the DPP-4 inhibitor medicine, their symptoms were relieved, usually in less than a month. Some patients developed severe joint pain again when they restarted the same medicine or another DPP-4 inhibitor.”
Analysts note that this is potentially very bad news for Merck, whose Januvia/Janumet has been hit with significant generic and biosimilar competition. Apparently 28 of the 36 cases of joint pain associated with DPP-4 inhibitors were related to Januvia. Five were linked to Onglyza, two to Tradjenta and one to Takeda Pharmaceuticals ’s Nesina (alogliptin).
In a statement, Merck noted that Januvia had been on the market longer than any of the other DPP-4 medications. It also accounts for about 80 percent of all DPP-4 prescriptions in the U.S. The company pointed out that the increase in incidents of joint pain is associated with the large number of prescriptions and that it is “confident in the safety profile of sitagliptin.”
Emily Geary, a spokeswoman with Boehringer Intelheim states that clinical trials of Tradjenta “do not show an imbalance between Linagliptin and placebo in musculoskeletal and connective tissue disorders or, more specifically, in joint disorders.”
An AstraZeneca spokesman, Andrew Davis, said it “works with health authorities and scientific experts to help ensure patients and physicians have a clear understanding of the risk benefit profile of our medications.”
Merck recently reported data from clinical trials that evaluated the cardiac safety of Januvia, along with a study of Vytorin. The data met the primary endpoint of not increasing the risk of cardiovascular events in diabetic patients compared to placebo. The company hopes the data will show the long-term benefit of Januvia, particularly in light of competition from a new class of diabetes drugs called SGLT-2 inhibitors.
In February, the FDA approved Glyxambi (empagliflozin/linagliptin) for type 2 diabetes. The drug is an SGLT-2 inhibitor manufactured by Eli Lily and Company and Boehringer Ingelheim.
“Today’s medical community recognizes the need to treat type 2 diabetes from multiple fronts to help patients improve glycemic control,” said Paul Fonteyne, president and chief executive officer of Boehringer Ingelheim in a statement at the time. “With Glyxambi, the dual inhibition of DPP-4 and SGLT2 — two proven targets in the treatment of type 2 diabetes — now provides U.S. physicians and patients with an option to simultaneously address multiple pathways to improve glycemic control.”
Merck and other companies cited in the FDA warning may find sales dropping as a result, even though the incidence of joint pain is quite minuscule compared to the number of people taking the drugs. Analysts in particular seem concerned as to whether Merck’s Januvia will be impacted, even though it seems likely that a bigger effect will be a competitive, more effective class of medications.