AbbVie has scored another key trial win with its blockbuster-in-waiting JAK1 inhibitor upadacitinib (ABT-494), but a death and pulmonary embolism take some of the shine off the data.
The phase 3 SELECT-MONOTHERAPY study looked at upadacitinib on its own in patients with moderate to severe rheumatoid arthritis (RA) who were not helped by methotrexate, an older, standard drug for the disease.
Results showed that after 14 weeks of treatment, both once-daily doses of upadacitinib (15 mg and 30 mg) met the study's primary endpoints of ACR20 and low disease activity (LDA) versus continuing prior stable methotrexate therapy.
Both doses also achieved “all key secondary endpoints,” the company said in a statement.
The study showed that at week 14, 68/42/23 percent of patients who switched to 15 mg once-daily upadacitinib and 71/52/33 percent of patients who switched to 30 mg once-daily upadacitinib hit an ACR20/50/70 response, compared to 41/15/3 percent of patients continuing on methotrexate.
And low disease activity was achieved by 45% and 53% of patients in the 15 mg and 30 mg groups, respectively, compared to 19% of patients continuing on methotrexate.
Clinical remission, meanwhile, was achieved by 28% and 41% of patients in the 15 mg and 30 mg groups, respectively, compared to just 8% of patients continuing on methotrexate.
But there were some serious adverse events, with one patient, who AbbVie says had “pre-existing cardiovascular risk factors,” dying of a hemorrhagic stroke caused by a ruptured aneurysm while on the lower-dose form of its med.
There was also one event of pulmonary embolism (PE) in the study, which also happened when the patient was taking the lower dose 15 mg dose. Again, AbbVie says the patient had “pre-existing risk factors for PE.”
The company stressed: “Across the SELECT rheumatoid arthritis program, including both the placebo-controlled and extension periods, the rate of deep vein thrombosis and PE remains consistent with the background rate for the RA patient population.”
This year, the experimental drug hit new heights in eczema and has already bested placebo in reducing symptoms of the disease back in the summer.
This med, alongside other JAK inhibitors, are looking to rival injected biologics, which includes Amgen’s Enbrel and AbbVie’s own major $14-billion-a-year Humira. Pfizer's Xeljanz, an oral JAK inhibitor, brought in almost $1 billion in 2016.
Analysts at Jefferies said that its midstage data for eczema, released in the fall, suggest that the orally active drug seems comparable to IL-4 and IL-13 blocker Dupixent (dupilumab)—which is given by injection—although they stress that no head-to-head comparison data is available.
They have previously said the drug could become a $3.5 billion product if it claims approval in other inflammatory conditions, including rheumatoid arthritis and inflammatory bowel disease, which the drug is already in trials for.
“The positive results from the SELECT-MONOTHERAPY study are encouraging, as they are the first evidence to support the potential of upadacitinib as a therapy without the need for background methotrexate,” said Michael Severino, M.D., EVP research and development and chief scientific officer at AbbVie.
“These findings add to the growing body of data showing the potential for upadacitinib as a meaningful treatment option for patients suffering from rheumatoid arthritis. We look forward to sharing additional data from the upadacitinib phase 3 rheumatoid arthritis program with the scientific community in 2018.”
This is the third of six studies in the so-called SELECT rheumatoid arthritis clinical trial program; more detailed data are coming from this test next year.