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.”

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

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Janet Woodcock and Joshua Sharfstein (AP, Images)

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Andrew Allen (Gritstone)

As coro­n­avirus vari­ants trig­ger new alarms, the NIH is putting an un­der-the-radar ‘next-gen’ vac­cine in­to PhI

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The IPO queue adds 5 more biotechs hop­ing to ring in 2021 by blitz­ing Nas­daq

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