- A large safety study has found that patients given Xeljanz, a Pfizer drug approved for various inflammatory diseases, had health issues like major heart complications and cancer at a higher incidence than those who got a different kind of anti-inflammation drug. The results could spell trouble for Xeljanz and other drugs that work in a similar way, according to analysts.
- Pfizer's study enrolled nearly 4,400 rheumatoid arthritis patients who were at least 50 years old and had at least one other cardiovascular risk factor. The main goal was to analyze malignancies as well as major adverse cardiovascular events, and see whether Xeljanz was as safe as a TNF inhibitor — the class of drugs which includes AbbVie's Humira and Amgen's Enbrel.
- Results show that among Xeljanz-treated patients, 98, or 3.37%, had a major cardiovascular event sometime between when they started treatment to 60 days after they stopped. In the TNF group, 37, or 2.55%, experienced such an event. Malignancies, excluding non-melanoma skin cancer, were seen in 122, or 4.19%, of patients given Xeljanz and 42, or 2.89%, of patients given a TNF inhibitor. With regard to Xeljanz, Pfizer said heart attack and lung cancer were the most frequently reported major cardiovascular events and malignancies, again excluding non-melanoma skin cancer.
First approved in 2012, Xeljanz has become the backbone of Pfizer's inflammation and immunology business. Revenue from the drug totaled $1.74 billion across the first nine months of 2020, a 6% increase from the same period from the year prior.
Yet, the sales growth has been met with rising concerns about safety.
Xeljanz works by blocking JAKs, or Janus kinases, a kind of enzyme that regulates immune cells. While this effect has made JAK drugs useful tools in the fight against inflammatory diseases like rheumatoid arthritis and ulcerative colitis, the fear is that they might also impair the body's ability to defend itself against harmful microbes or cancer.
Regulators like the Food and Drug Administration have taken these fears seriously. When Xeljanz was first approved, the FDA mandated a black box warning on the drug's label, flagging the potential for serious infections and malignancy. Then in 2019, the agency expanded that boxed warning to include increased risk of blood clots and death for the higher, 10 mg twice daily dose of Xeljanz.
The safety troubles have expanded beyond Xeljanz too. Newer JAK drugs such as Eli Lilly's Olumiant and AbbVie's Rinvoq also carry warnings of serious infection, malignancy and thrombosis.
For Pfizer, the large study comparing Xeljanz to a TNF inhibitor — which was required by the FDA — was one path toward easing these worries. The initial results released Wednesday, however, suggest that could now be a more challenging task.
Brian Abrahams, an analyst with RBC Capital Markets, notes that Pfizer's readout could make the FDA "even more risk-averse" when it comes to labeling decisions on JAK drugs, which could then benefit rival drug companies working on different approaches to curbing inflammation.
Abrahams detailed in a note to clients that Pfizer's results could weigh on an experimental drug from the Belgian biotech company Galapagos, as well as Incyte, which is working to get a topical version of its JAK drug Jakafi approved. At the same time, the results could open the door for non-JAK programs in development at Galapagos and Gilead, Abrahams argues.
"We believe that extensive additional analyses of these study data, and communicating them as soon as possible, will further clarify the benefit and risk profile of [Xeljanz] to help inform medical decision making and patient care," said Tamas Koncz, Pfizer's chief medical officer for inflammation and immunology, in a Jan. 27 statement.
Pfizer shares were down 2% in late morning trading Wednesday.