Like two crafty boxers, Albireo and Mirum Pharmaceuticals are bobbing and weaving, answering punches with counterpunches, in their battle to treat a trio of pediatric liver diseases with their respective ileal bile acid transporter (iBAT) drugs.
Two weeks after Albireo reported positive phase 3 results in Alagille syndrome (ALGS) for its drug Bylvay, Mirum has one-upped its rival by turning in positive results in progressive familial intrahepatic cholestasis (PFIC) for its treatment Livmarli.
Making their competition that much more interesting is that while Albireo already owns an approval in PFIC, Mirum has gained one in ALGS. These nods came two months apart last year. Now both drugs are set up for FDA approvals in the diseases they don't already treat.
The hereditary conditions cause a buildup of bile acid in the liver, requiring patients to undergo transplants to stay alive. Life expectancy is shorter with PFIC, with only 50% of patients making it past age 10.
As for Livmarli’s new study results, the phase 3 March trial enrolled 93 PFIC patients under the age of 18. Livmarli delivered statistically significant improvements in the relentless itching (pruritis) that accompanies the condition versus placebo. It also provided more bile acid clearance from the liver.
But the biggest takeaway for Mirum chief scientific officer Pamela Vig, Ph.D., was the effect triggered by higher dosing compared to that in the company’s previous phase 2 trial.
“It has had an incredible effect, where we see a doubling of the serum bile acid reductions,” Vig said in an interview.
In addition, Livmarli delivered a 1.8-point improvement over placebo on a scale that measures a patients' itch symptoms, Vig said. A 1-point improvement and above is "clinically meaningful," she noted
"I don’t think even we were expecting to see that sort of effect," Vig added.
In the study, patients were given 570 micro-grams of treatment per kilogram of body weight twice a day. In the previous study, patients received 266 micro-grams per kilogram of body weight once a day. Then later in that study, patients were given that dose twice daily.
“We knew that if we were to increase the dosing hypothesis, that we may see a greater proportion of responders and that played out,” Vig said.
Pushing the dosage higher has given Livmarli a competitive edge over Bylvay, according to analysts at Evercore ISI. While warning that cross-trial comparisons are far from conclusive—especially for different indications—the analysts point to Livmarli’s advantages over Bylvay in response rate (62% versus 35%), pruritis score (-1.8 versus -1.1) and serum bile acid changes.
In the second quarter, Livmarli generated sales of $17.5 million in treating the larger patient population in ALGS. Bylvay garnered $5.9 million in sales during that period in PFIC. Evercore projects peak sales potential for Livmarli in ALGS alone at $850 million.
Both companies are developing their iBAT inhibitors to treat another pediatric liver disease, biliary atresia (BA), which has the largest patient population. Mirum plans to read out a phase 2 trial in that indication next year, while Albireo’s phase 3 study readout is expected in 2024.
“Mirum continues to remind us of the importance of execution and as such may be able to make more out of PFIC’s unmet need,” the Evercore ISI analysts said. “This will become relevant again as the two companies are gearing up to compete in BA.”