ASH: As Novartis enters PNH market, AstraZeneca shows longer term effect of its latest contender

The week after Novartis secured a foothold in the paroxysmal nocturnal hemoglobinuria (PNH) market, AstraZeneca has released new data from its own attempt to find fresh ways of tackling this rare blood disease.

AstraZeneca’s danicopan is intended to be used as an add-on to Big Pharma’s established PNH players Ultomiris and Soliris. A readout from the phase 3 ALPHA study back in September 2022 met the primary endpoint of changing hemoglobin levels from baseline at 12 weeks for a specific group of PNH patients who experience extravascular hemolysis (EVH).

Now, AstraZeneca has released long-term follow-up data at the American Society of Hematology annual meeting showing that the improvements in mean hemoglobin levels and absolute reticulocyte count levels were maintained at 48 weeks.

Specifically, there was a 3.17 g/dL change in baseline hemoglobin levels at 24 weeks compared to the 2.94 g/dL change recorded after 12 weeks. Meanwhile, the 83.8 drop in absolute reticulocyte count recorded at 12 weeks was also similar to the 80.2 drop from baseline still being recorded at 24 weeks.

When it came to avoiding the need for a blood transfusion, 83% of patients hadn’t required this procedure after 12 weeks, falling slightly to 78% of patients at the 24-week mark.

“These new data further demonstrate the potential of danicopan as an add-on to Ultomiris or Soliris to address the needs of the small subset of patients with PNH who experience clinically significant EVH,” Trial Investigator Austin Kulasekararaj, M.D., said in the Dec. 11 release.

“Expanding on positive 12-week results, the findings demonstrate sustained improvements in hemoglobin levels for up to 48 weeks, while also maintaining disease control, as measured by lactate dehydrogenase levels,” Kulasekararaj added.

In this morning’s release, AstraZeneca said that “regulatory submissions for danicopan are currently under review with multiple global health authorities.” The company hasn’t yet announced timelines for the U.S. or Europe—where danicopan has been granted breakthrough therapy designation and priority medicine tags, respectively—although a spokesperson told Fierce Biotech that decisions on the submissions that have been made to various regulators are expected in the first half of next year.

The dominance of the C5 inhibitors Ultomiris and Soliris in PNH was one of the reasons AstraZeneca’s $39 billion acquisition of the rare-disease-focused Alexion looked like such a good move in 2020. The rare, acquired, life-threatening disease is characterized by destruction of red blood cells, blood clots and impaired bone marrow function. Soliris became the first FDA approved therapy for the condition in 2007, followed in 2018 by Ultomiris, which requires fewer intravenous infusions.

However, other pharmas are catching up, most notably Novartis, which secured FDA approval for its potential “pipeline in a pill” iptacopan to treat PNH last week. As well as acting upstream of the C5 terminal pathway that is targeted by Ultomiris and Soliris, iptacopan’s oral administration also gives it an edge over the injections or infusions required by C5 inhibitors. Meanwhile, Roche is awaiting an FDA decision on its antibody crovalimab in PNH.

Danicopan formed part of AstraZeneca’s “factor D program,” which aimed to retain the company's PNH crown by inhibiting an enzyme called factor D to help a specific group of PNH patients whose EVH results in anemia, despite being on Ultomiris or Soliris. However, the other half of the program, a molecule vemircopan, had its PNH plans scrapped recently due to a lack of efficacy in a phase 2 trial.