Alexion Pharmaceuticals expects only modest initial sales gains from FDA approval of Soliris (eculizumab) for atypical hemolytic uremic syndrome (aHUS) due to the devastating natural course of the disease and the small quantity of drug used to treat pediatric patients.

FDA granted accelerated approval to Soliris, a terminal complement inhibitor, for adults and children with aHUS on Sept. 23. It is the first drug approved for this condition, in which blood clots in small blood vessels throughout the body can lead to kidney failure, stroke, heart attack and death.

The approval date offered a double dose of good news for Alexion, as the European Union's Committee for Medicinal Products for Human Use issued a positive opinion on an aHUS indication the same day (Also see "Optimer's Fidaxomicin Among Three NMEs Given Positive Review By Europe's Regulators" - Pink Sheet, 23 September, 2011.).

Atypical aHUS accounts for 5% to 10% of all cases of hemolytic uremic syndrome, and the disease disproportionately affects children, FDA said. The current standard of treatment is plasma or fresh frozen plasma infusion.

The indication is Soliris' second in an ultra-orphan population. The drug first received FDA approval in 2007 for treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) (Also see "Alexion Biologic Soliris Is First To Get FDA Nod For Rare Blood Disease" - Pink Sheet, 19 March, 2007.).

The drug is priced at approximately $400,000 a year for treatment in PNH, and has performed well for the company (Also see "Alexion Soars On Strong Q2 Soliris Sales" - Pink Sheet, 21 July, 2011.). However, the additional indication is not likely to have much of a near-term impact on sales.

Ultra-Orphan Population Reflected In Small Study Sizes

The condition's rarity is reflected by the size of the clinical trial database supporting approval in aHUS. Accelerated approval was based on two single-arm trials in a total of 37 adult and adolescent patients, ages 13-68 years old.

In the aHUS studies, patients experienced a reduction in terminal complement activity and an increase in platelet count following initiation of treatment. Renal function was maintained or improved.

The clinical trial data were supported by results from a retrospective study that included 19 pediatric patients ages 2 months to 17 years.

Two ongoing, open-label trials will serve as confirmatory studies, using the same endpoints as the completed clinical trials, Alexion said. One study is targeted to enroll 15 pediatric patients, while the second study is slated to enroll 30 adult patients. Both began in 2010 and are expected to complete in mid-2012, according to ClinicalTrials.gov.

Devastating Disease Course Means No "Pent-Up Demand"

During a Sept. 26 conference call to discuss the aHUS approval, company officials sought to temper any expectations that the new indication would result in a quick, sharp rise in sales.

The prevalence of aHUS appears to be lower than that of PNH, and this is reflected in the clinical trial databases supporting the two indications, company officials said, noting that the PNH indication was premised upon clinical trials encompassing 195 patients. Furthermore, only a small percentage of patients in the aHUS studies were from the U.S.

The devastating natural course of the disease also limits the population eligible for treatment.

Despite current supportive care, more than half of aHUS patients not treated with Soliris die, require dialysis or suffer permanent kidney damage within one year of diagnosis, company officials said.

"We don't see any likelihood or possibility of what others describe as pent-up demand where there's a large number of patients waiting to obtain treatment," Alexion CEO Leonard Bell said. "Given the severity of the disease, that's not an option."

The disease's strong pediatric component also will limit Soliris' sales growth.

Unlike with the PNH indication that primarily affects adults, Alexion expects that a significant proportion of aHUS patients will be children or infants, for whom dosing is weight-based and amounts to a fraction of the adult dose in either indication.

Bell estimated that for the smallest children with aHUS, the dose would be one-quarter to one-fifth of the adult aHUS dose, and one-third to one-quarter of the adult PNH dose. This means that substantially fewer vials of drug will be required to support the youngest patients.

As a result, Alexion management is predicting initial sales growth from the aHUS claim will be gradual, with longer-term growth pegged to obtaining ex-U.S. approvals for the use.

Soliris is Alexion's first and only marketed product. Concurrent with the FDA approval and CHMP positive opinion, Alexion announced it had raised its 2011 revenue projections from the previous range of $745- $755 million to $760-$768 million. The firm also revised its non-GAAP earnings per share guidance upward to $1.15-$1.20 from the previous range of $1.10-$1.15.

Alexion attributed the revisions to stronger growth in PNH sales in the U.S., Western Europe and Japan, rather than to any expectation with regard to aHUS sales.

"The impact of our new aHUS indication is expected to be modest in 2011 and is included in our 2011 guidance," Senior Vice President and Chief Financial Officer Vikas Sinha said.

-Sue Sutter (s.sutter@elsevier.com)

Alexion's Soliris Gains New Orphan Indication But Limited Sales Expectations

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