FDA Action Alert: BMS, GSK, Ironwood, Ipsen/Albireo

FDA Action Alert

Pictured: FDA Action Alert logo/@Nicole Bean for BioSpace

The FDA has four target action dates on its schedule this week, including ones in cardiomyopathy, functional constipation, myelofibrosis and Alagille syndrome.

Ironwood Pushes Gut Drug to Pediatric Setting

On June 14, the FDA is set to release its verdict on Ironwood Pharmaceuticals’ supplemental New Drug Application (sNDA), in which the company proposes to use Linzess (linaclotide) for the treatment of functional constipation in kids and teens aged 6–17 years.

Ironwood is developing and commercializing Linzess in collaboration with AbbVie, following a 2015 agreement with Allergan. AbbVie acquired Allergan in 2019.

Linzess is a guanylate cyclase-C (GC-C) agonist that works by binding to the GC-C receptor within the intestinal epithelium, which in turn increases fluid secretion, faster transit and lower pain-sensing in the intestine. The drug won the FDA’s approval in August 2012 to treat patients with chronic idiopathic constipation and irritable bowel syndrome with constipation in adults.

Linzess’s label bears a boxed warning for risk of serious dehydration when used in children under two years of age.

Ironwood supported Linzess’ sNDA with data from a large Phase III study assessing the drug in pediatric patients. With 330 participants, the trial found that 12 weeks of Linzess treatment led to statistically significant and clinically meaningful improvements in spontaneous bowel movement, as compared with placebo.

Moreover, patients in the Linzess arm also saw better stool consistency at the 12-week follow-up. Ironwood’s drug was also safe, with the most common side effect being diarrhea.

When it accepted Ironwood’s sNDA, the FDA granted Linzess Priority Review, shortening its review time by four months.

Ipsen/Albireo Look to Add Rare Genetic Disease to Bylvay’s Label

In February 2023, the FDA accepted an sNDA submitted by Albireo, seeking to add the rare genetic disease Alagille syndrome to Bylvay (odevixibat)’s label. The target action date is June 15. Albireo entered into an agreement in January to be acquired by Ipsen

Alagille syndrome is a heritable condition characterized by the lack of bile ducts that drain the liver, leading to the accumulation of bile, which ultimately causes organ damage. The disease can also affect the heart, skeleton, eyes, kidneys and central nervous system. Common symptoms include yellow skin or eyes, stunted growth and severe pruritus.

Bylvay’s Alagille bid is supported by data from the Phase III ASSERT study, a double-blinded, randomized and placebo-controlled trial that enrolled more than 50 participants across 32 trial sites in North America, the Middle East, Europe and the Asia-Pacific region.

In the study’s main analysis, Bylvay significantly reduced pruritus after 6 months of treatment as compared with placebo, thereby meeting ASSERT’s primary endpoint. The drug also significantly lowered serum bile acid levels and improved sleep parameters, according to Albireo.

As for safety, ASSERT found Bylvay to be well-tolerated, with a side effect profile that was comparable to placebo. None of the patients dropped out due to toxicities.

The FDA also granted Bylvay’s sNDA its Priority Review designation.

BMS Seeks Another Indication for Camzyos

The FDA will release its verdict on June 16 regarding Bristol Myers Squibb‘s sNDA proposing to use its heart drug Camzyos (mavacamten) to lower the need for septal reduction therapy (SRT) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

Currently, many patients suffering from HCM need to undergo SRT, Roland Chen, senior vice president and head of cardiovascular development, Global Drug Development at BMS, said in a statement upon the FDA’s acceptance of the sNDA. SRT is either an open-heart surgical procedure or a catheter-based operation.

BMS supported Camzyos’ sNDA with data from the Phase III VALOR-HCM study, a randomized, double-blinded and placebo-controlled trial that enrolled 112 patients with symptomatic obstructive HCM. All participants were qualified for SRT and had been referred for the operation.

VALOR-HCM’s primary endpoint was a composite between the number of patients who decided to push through with SRT by week 16 and the number of patients who remain eligible for SRT as determined by their left ventricular outflow tract (LVOT) gradient and New York Heart Association classification.

Key secondary endpoints included exercise gradient LVOT and serum biomarkers after 16 weeks of treatment. Camzyos cleared all primary and secondary endpoints “with a high degree of statistical significance,” according to BMS’s announcement.

GSK Awaits Approval for Myelofibrosis Hopeful

The FDA’s final action date this week is for GSK’s investigational drug, momelotinib, which the company is proposing to treat myelofibrosis patients with anemia. The decision is set to be released by June 16.

According to GSK, momelotinib works through a differentiated mechanism of action that involves the inhibition of three signaling pathways: the JAK1 and JAK2 cascades, as well as the activin receptor type I (ACVR1) pathway. By disrupting JAK1 and JAK2 signaling, momelotinib induces improvements in patient constitution and symptoms of splenomegaly. Meanwhile, its ACVR1 activity could decrease levels of hepcidin, which contribute to anemia in myelofibrosis.

Data from the pivotal Phase III MOMENTUM trial supported momelotinib’s FDA bid. In December 2022, GSK reported 48-week results from MOMENTUM at the 64th American Society of Hematology (ASH) Annual Meeting. Momelotinib achieved its primary efficacy endpoint of an at-least 50% reduction in Total Symptom Score after 24 weeks.

GSK’s myelofibrosis candidate also met key secondary endpoints including transfusion independence and splenic response rate, both likewise measured at 24 weeks.

MOMENTUM is a randomized and double-blinded clinical trial that randomized nearly 200 patients, at a 2:1 ratio, to receive either momelotinib or danazol, a common treatment used in myelofibrosis. At 24 weeks, patients on danazol were allowed to switch to momelotinib.

Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com

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