Crohn’s disease can be treated with medications that control inflammation and reduce the frequency of flareups for the intestinal disorder. These treatments include biologic drugs that target certain immune system proteins. However, these therapies are inadequate for some patients. The FDA has approved a currently available AbbVie drug for Crohn’s disease, marking a new first for treatment of the disorder.

The regulatory nod goes to risankizumab, a drug that North Chicago, Illinois-based AbbVie already sells under the name “Skyrizi” for approved uses in plaque psoriasis and psoriatic arthritis. Skyrizi is an antibody designed to bind to interleukin-23 (IL-23). This cytokine, or cell-signaling protein, is associated with one of the ways that inflammation develops in the body. By binding to it and blocking it, Skyrizi stops IL-23 from sparking pro-inflammatory activity. The additional drug approval announced Friday covers use of Skyrizi in adults with moderately to severely active Crohn’s disease. It’s the first drug targeting IL-23 that is approved for this indication.

Skyrizi’s latest approval is based on the results of two pivotal studies that compared the AbbVie drug to a placebo. The drug was dosed as a hourlong 600 mg infusion at the start of the study and then as a 360 mg dose via injection from a prefilled syringe at week 12 and then every eight weeks from then on. The main study goals were to show a reduction in the signs of the disease as observed via endoscopy and to assess clinical remission, which is a reduction of disease symptoms to the point of where they are nearly gone.

AbbVie reported that significantly more patients in the Skyrizi group achieved both study goals compared to those given a placebo. In a 52-week maintenance study, AbbVie reported that significantly more patients achieved both main goals compared with the placebo group. Results from two pivotal Phase 3 tests of the drug in Crohn’s disease were published in May in The Lancet.

“In both the induction and maintenance clinical trials, a significantly greater number of adult patients saw few or no symptoms and a meaningful reduction of visible signs of intestinal inflammation, compared to placebo,” Marla Dubinsky, chief, division of pediatric gastroenterology for the Mount Sinai Health System and co-director of the Susan and Leonard Feinstein IBD Center at Mount Sinai said in a prepared statement. “This approval provides healthcare professionals with a greatly needed additional option for treating the disruptive symptoms of Crohn’s disease.”

Dubinsky is a paid consultant and advisor to AbbVie.

The most common side effects reported from the Crohn’s disease studies include fever, headache, and anemia. The drug does introduce more serious risks. Like other medications that suppress the immune system, Skyrizi increases the risk of infections. Upper respiratory infections are listed among the more common side effects of the drug. Also, one participant who received two doses of Skyrizi in the Crohn’s disease study developed drug-induced liver injury and rash that required hospitalization. The drug’s label cautions clinicians to monitor for signs of liver problems up to at least 12 weeks of treatment.

Since Skyrizi’s initial approval in 2019 for moderate-to-severe plaque psoriasis, sales of the drug have grown steadily. Skyrizi accounted for $2.9 billion in global sales last year, a nearly 85% increase over the prior year. Earlier this year, the FDA approved Skyrizi as a treatment for active psoriatic arthritis, the second approved indication for the product.

AbbVie is developing other treatments for Crohn’s disease. Rinvoq, a small molecule JAK inhibitor, is in late-stage development for the disorder. In February, AbbVie reported the drug met the main goal of the second of two Phase 3 studies in moderate-to-severe Crohn’s disease.

Rhythm Pharmaceuticals obesity drug lands another FDA nod

In other supplemental drug approval developments, Rhythm Pharmaceuticals received good news and bad news regarding its weight management medicine, Imcivree. The FDA on Friday awarded an additional approval for that drug as a treatment for Bardet-Biedl syndrome (BBS), a rare inherited disorder that causes insatiable hunger and in turn, severe obesity. However, the agency turned down the biotech’s application to expand the drug’s approval to a different disorder.

Imcivree is a peptide designed to target melanocortin-4 receptor (MC4R), a protein in the brain that’s key to a pathway that regulates hunger and energy expenditure, which in turn affects weight. The drug was first approved in 2020 for weight management in three rare genetic disorders that lead to obesity: pro-opiomelanocortin deficiency, proprotein subtilisin/kexin type 1 deficiency, and leptin receptor deficiency.

In BBS, Imcivree is intended to restore the function of the MC4R pathway to reduce hunger and weight. Phase 3 results in BBS showed that the drug met the weight and hunger reduction clinical trial goals. In patients age 6 and older with obesity caused by BBS, the Rhythm drug led to an average 7.9% reduction in body mass index without diet or exercise. By comparison, the average BMI reduction was 4.5% in the placebo group. In patients 12 and older, Rhythm also reported a statistically significant change in score according to a scale used to assess hunger.

The ultra-rare nature of Imcivree’s approved indications means that the drug is not yet a big seller. Rhythm reported $3.1 million in 2021 revenue from the drug. But Imcivree represents a “pipeline in a product.” The company is running mid-stage clinical trials testing the drug in 10 other genes that are related to the MC4R pathway. However, Rhythm has missed out on adding another rare disease to Imcivree’s list of approvals. The FDA rejection announced Friday was for Alström syndrome, yet another genetic disorder that can lead to hunger and obesity. Rhythm said it plans to review potential paths forward for Imcivree in that indication.

Photo by AbbVie