Rare Diseases, Results

After securing quick OK for PNH patients, Alexion’s Ultomiris succeeds in aHUS pivotal study

About a month after the FDA gave Alexion a Christmas present in the form of an early approval for its rare blood disorder drug, Ultomiris, for patients with PNH, the drugmaker has reported positive pivotal data evaluating the monoclonal antibody in a single-arm study involving atypical hemolytic uremic syndrome (aHUS) patients.

The Boston-based biotech is now prepping regulatory submissions in the United States, EU and Japan for Ultomiris. The drug is Alexion’s shot at protecting its blockbuster blood disorder franchise that is currently centered around its flagship drug, Soliris, which is a complement inhibitor typically administered every two weeks. Ultomiris has a similar mechanism of action but requires less-frequent dosing — every eight weeks.

aHUS is a chronic, progressive ultra-rare disease that can lead to potentially irreversible damage to kidneys and other vital organs and can be fatal. It is characterized by inflammation and the formation of blood clots in small blood vessels throughout the body, or thrombotic microangiopathy (TMA).

In the 56-patient late-stage study involving adults who had not been previously treated with a complement inhibitor, 53.6% of patients (95% CI [39.6%, 67.5%]) demonstrated complete thrombotic microangiopathy (TMA) response after treatment with Ultomiris in the initial 26-week treatment period — meeting the main goal of the study.

Soliris’ label indicates the drug achieved a 56% and 64% TMA response rate in adult and pediatric aHUS patients.

This data is “broadly comparable to existing Soliris data in similar patient populations, but with added convenience of every 8 week dosing. Alexion still has another Ultomiris phase III study outstanding in pediatric and adolescent aHUS, which is expected in the next few months,” Leerink’s Geoffrey Porges wrote in a note.

The news “essentially de-risks the near term clinical aspects of Alexion’s life cycle management strategy for their $3.5 billion complement franchise. We expect adoption of UItomiris to be even faster in aHUS than PNH given the substantial administrative benefit of Ultomiris (Q8 vs Q2 week dosing) and the cost savings for payers from Ultomiris’ price (~$475,000 vs ~$700,000) compared to Soliris.”

In December, Alexion said it would price Ultomiris at a discount to Soliris, which has long been one of the most expensive therapies on the block. In an SEC filing last month, the drugmaker disclosed Ultomiris would carry a list price of $6,404 per vial, versus Soliris that is priced at $6,543 per vial. The FDA has imposed a black box warning — the agency’s most severe — on both drugs.

The company’s shares $ALXN inched about 3% lower in early Monday trading. “If investors react negatively to the apparent similarity of the Ultomiris result (54% response) to the Soliris result in a much earlier trial (65% response) or to the safety events in this study, we would recommend taking advantage of that weakness given the growing tail value of the company’s future cash flows,” Porges added.

Credit Suisse’s Martin Auster, in a note ahead of the Phase III results, said he expected a bulk of Soliris patients would switch to Ultomiris in the coming years.

He modelled a roughly “80% conversion from Soliris to Ultomiris for the PNH/aHUS franchise in 3-4 years in the US/ex-US, respectively.”

Other drug developers are also developing treatments for the blood disorders that could potentially eat into sales. But Auster noted that aHUS is “a more challenging indication for competitors to enroll clinical trials, considering the disease severity, importance for early treatment to avoid organ damage, and well-established efficacy with Soliris. ALXN benefits from orphan drug protection in the EU until 2023 possibly pushing a biosimilar launch in the indication into 2024/2025. The company also has composition of matter patents in the US/JP out to 2027.”


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Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

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