AstraZeneca's Ultomiris scores its 3rd FDA approval, setting up market clash with argenx

Replacing a superstar can be difficult, except for the uber talented. Case in point: the Green Bay Packers’ Aaron Rodgers stepping in at quarterback for Brett Favre and not missing a beat.   

In the pharma arena, Alexion’s blossoming rare disease standout Ultomiris is showing it has the right stuff to take the reins from aging mainstay Soliris.

Thursday, Ultomiris continued its rapid ascent with an FDA approval to treat generalized myasthenia gravis (gMG), an autoimmune neuromuscular disorder that causes severe weakness and loss of muscle function.

It is the third FDA nod for Ultomiris, which achieved blockbuster status in just its second full year on the market following green lights in 2018 to treat paroxysmal nocturnal hemoglobinuria (PNH) and 2019 for atypical hemolytic uremic syndrome.

In gMG, Ultomiris will compete with argenx's recently approved Vyvgart. A Spherex survey of U.S. neurologists from February showed that 51% perceived Vyvgart to “offer a substantial advance over other currently available therapies.”

As Ultomiris has added indications—all covered by Soliris—it has enticed users of the forerunner to switch. One edge is convenience as Ultomiris is infused every eight weeks for 45 minutes as opposed to every two weeks for Soliris for two hours per visit.

Another edge is cost as Ultomiris is priced lower—though not by much—than Soliris, which ranked No. 10 last year among the most expensive drugs in the U.S. at more than $678,000 annually, according to GoodRx.

The availability of Ultomiris has led to a conversion rate of more than 70% in major markets for PNH, Alexion CEO Marc Dunoyer said in a preapproval interview this week.

“With all the advantages that Ultomiris has over Soliris, we feel it’s great news for the company,” Dunoyer said of the FDA nod. “We have been the pioneer in the immunology field for the complement inhibitor and we continue to lead the pack.”

The FDA based Ultomiris’ gMG approval on phase 3 data showing sustained improvement for patients over placebo for 26 weeks in accomplishing daily activities, in muscle strength and in overall quality of life.

There are an estimated 90,000 people in the U.S. with gMG. Dunoyer said Ultomiris has the potential to serve a wider range of patients than Soliris because it can be provided at an earlier stage of the disease and to those with a milder form.

“Earlier intervention can preserve function and quality of life," James Howard Jr., M.D., the trial’s lead investigator of the University of North Carolina School of Medicine, said in a release. "This approval offers patients, including those with milder symptoms, a long-acting C5 inhibitor with early onset and reliable efficacy."

Dunoyer also highlighted the ability of Ultomiris as a long-acting drug to keep patients on an even keel. In Alexion's extension study, Ultomiris continued to help patients through 52 weeks. 

“Patients were really fearing the unpredictability of treatment and episodes of crisis,” Dunoyer said. “When you have very stable, robust efficacy over a long period of time, it’s a great benefit for patients.”

As Ultomiris’ revenues have grown, sales of Soliris—which first hit the market in 2007—have continued to hold their own. While Soliris has lost patients to the newer drug, it also has gained others by adding an approval in 2019 for neuromyelitis optica spectrum disorder (NMOSD).

By the time Soliris loses its patent protection in 2027, Ultomiris is likely to have usurped most of its patients, and the hit from generic competition should be minimal.

The prospects of the powerhouse pair of C5 inhibitors helped convince AstraZeneca to purchase Alexion for $39 billion in December of 2020.

As for the future of Ultomiris, AZ expects regulatory decisions on gMG to come in the second half of this year in Europe and Japan.

The only other indication left for Ultomiris to conquer to match Soliris is NMOSD. AZ expects trial results in the first half of this year, with regulatory filings anticipated in the second half of 2022.