Apellis Rare Blood Disease Drug Tops Alexion’s in Head-to-Head Test

Xconomy Boston — 

Apellis Pharmaceuticals wants to offer patients who have an ultra-rare blood disease another treatment option. The drug developer Tuesday revealed late-stage clinical trial data suggesting its experimental therapy works better than a blockbuster Alexion Pharmaceuticals medicine that is currently the standard of care.

The Apellis (NASDAQ: APLS) drug, pegcetacoplan, is in testing as a treatment for paroxysmal nocturnal hemoglobinuria (PNH), a disease in which a part of the immune system destroys red blood cells, leading to blood clots and organ failure. Patients who have the disease require frequent blood transfusions to boost their red blood cell levels.

Apellis reported that its drug met the Phase 3 study’s main goal, which was to beat Alexion (NASDAQ: ALXN) drug eculizumab (Soliris) as measured by improvement in levels of hemoglobin, the oxygen-carrying protein in the blood. The company, which is based in Crestwood, KY, and has additional operations in Waltham, MA, also reported that patients treated with its drug required fewer blood transfusions during the study compared to those who received the Alexion drug.

Shares of Apellis jumped more than 21 percent to $36.59 apiece after the preliminary Phase 3 results were released Tuesday morning.

PNH is a disease caused by dysfunction within the complement system, a family of proteins that complement other parts of the immune system. The Alexion drug, an antibody, was developed to target and block a complement system protein called C5. This approach is intended to stop the complement system from rupturing red blood cells. Carrying a price tag of more than $500,000 a year, the Alexion drug is one of the most expensive medicines on the market. The drug, which is also approved for other rare disorders, generated more than $3.5 billion in total sales in 2018.

Speaking Tuesday on a conference call to discuss the pegcetacoplan clinical trial results, Apellis CEO Cedric Francois said that his company’s drug can halt the same complement system process that the Alexion drug does, as well as another one in which immune cells in the liver and spleen destroy red blood cells. The Apellis drug achieves this by targeting C3, a protein that’s upstream of C5 in the cascade of complement system proteins.

The Phase 3 study of pegcetacoplan enrolled 80 patients who had been treated with Alexion’s drug for at least three months. Patients were randomly assigned to receive the Apellis drug twice weekly, or the Alexion drug at their current dose. Apellis reported that patients given its drug showed a hemoglobin level increase of 2.4 grams per deciliter (g/dL) after 16 weeks. In the group given the Alexion drug, the change in hemoglobin was -1.5 g/dL. Francois added that 85 percent of patients in the pegcetacoplan group remained transfusion-free during the 16-week study, compared to 15 percent of patients in the eculizumab group.

“There is room for improvement in the quality of life for these patients and that is what we intend to do,” Francois said.

No patient deaths were reported in either group. The most common side effects for the Apellis drug were injection site reactions, diarrhea, headache, and fatigue. Francois said that full data from the pegcetacoplan PNH study will be published and presented later this year. The company plans to meet with the FDA in the first half of this year to discuss the drug’s path forward.

Meanwhile, a Phase 3 study of the drug in PNH patients who have not been treated with eculizumab is ongoing. Francois added that the company hopes the drug can become a platform for treating other complement system conditions. Pegcetacoplan is being tested in Phase 3 for geographic atrophy, a progressive degenerative eye disorder; in a Phase 1b/2 study in cold agglutinin disease, another rare disorder in which the immune system destroys the body’s own red blood cells; and in Phase 1b/2 for the rare kidney disease complement 3 glomerulopathy.

Despite the encouraging pegcetacoplan data, SVB Leerink analyst Dae Gon Ha sees a tough path for the Apellis drug to break into the market. In a Tuesday research note he wrote that eculizmumab is firmly established as a PNH treatment and Alexion is working to move patients treated with that drug to its successor, the antibody drug ravulizumab (Ultomiris). Ha added that the problems with eculizumab (anemia and transfusion dependence) that would cause patients to seek an alternative are less severe in PNH patients today, according to SVB Leerink’s checks with the medical community.

Alexion is also spreading its bets in the PNH space. In October, the company agreed to pay $930 million to buy Achillion Pharmaceuticals, which developed a PNH drug that works in a different way. That deal gives the company another drug to offer patients as an alternative to eculizumab.

Looking ahead, Ha sees challenges for Apellis’s ambitions to apply its drug to other disorders. Sanofi (NYSE: SNY) drug sutimlimab has positive Phase 3 data in cold agglutinin disease, and the drug could be submitted to the FDA for review later this year. That would leave the Apellis drug in an uphill battle for a second-to-market product, Ha wrote. He sees similar competitive pressures for the Apellis drug in other disorders as well.

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