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.”

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Fangliang Zhang (Imaginechina via AP Images)

The big mon­ey: Poised to make drug R&D his­to­ry, a Chi­na biotech un­veils uni­corn rac­ing am­bi­tions in a bid to raise $350M-plus on Nas­daq

Almost exactly three years after Shanghai-based Legend came out of nowhere to steal the show at ASCO with jaw-dropping data on their BCMA-targeted CAR-T for multiple myeloma, the little player with Big Pharma connections is taking a giant step toward making it big on Wall Street. And this time they want to seal the deal on a global rep after staking out a unicorn valuation in what’s turned out to be a bull market for biotech IPOs — in the middle of a pandemic.

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Len Schleifer (left) and George Yancopoulos, Regeneron (Vimeo)

Eyes on he­mo­phil­ia prize, Re­gen­eron adds a $100M wa­ger on joint de­vel­op­ment cam­paign with In­tel­lia

When George Yancopoulos first signed up Intellia to be its CRISPR/Cas9 partner on gene editing projects 4 years ago, the upstart smartly ramped up its IPO at the same time. Today, Regeneron $REGN is coming back in, adding $100 million in an upfront fee and equity to significantly boot up a whole roster of new development projects.

And they’re highlighting some clinical hemophilia research plans in the process.

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Jean-Jacques Bienaimé, BioMarin chairman and CEO

Bio­Marin holds the line on bleeds with 4-year val­rox up­date on he­mo­phil­ia A — but what's this about an­oth­er de­cline in Fac­tor 8 lev­els?

BioMarin has posted some top-line results for their 4-year followup on the most advanced gene therapy for hemophilia A — extending its streak on keeping a handful of patients free of bleeds and off Factor VIII therapy, but likely stirring fresh worries over a continued drop in Factor VIII levels.

We just don’t know how big a drop.

We’ll see more data when the results are presented at the World Federation of Hemophilia in a couple of weeks. But in a statement out Sunday night, BioMarin $BMRN reported that none of the patients required Factor VIII treatment, adding:

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As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Iterum's fu­ture looks un­cer­tain, af­ter lead an­tibi­ot­ic fails con­sec­u­tive piv­otal stud­ies

While the market for antibiotics remains in tatters — unlike many of its bankrupt (or at the brink of bankruptcy) peers — Iterum is suffering not because its antibiotic isn’t selling, but because the compound has now failed back-to-back late-stage studies.

The experimental drug, sulopenem, was designed to tackle drug-resistant infections with an outpatient focus (in addition to hospitals), to avert those reimbursement challenges that incentivize hospitals to prescribe cheaper, generic broad-spectrum antibiotics.

Covid-19 roundup: Did in­sid­ers cash in on pos­i­tive news re­port about Gilead be­fore pub­li­ca­tion?

A series of bullish trades on Gilead options just before the release of a favorable news story is raising questions among regulatory experts, Reuters reported.

On April 16, just hours before STAT published anecdotes from a Chicago hospital that served as one of the clinical sites to test Gilead’s remdesivir in Covid-19 patients, the California-based company’s shares were trading at around $75. Four large blocks of options were purchased for about $1.5 million each, betting that the stock would rise beyond that to as much as $87.5 by mid-August.

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Roche nabs front­line OK for Avastin/Tecen­triq in com­mon liv­er can­cer, best­ing an old Bay­er drug

For the first time in 12 years, the FDA has approved a new frontline treatment for the most common form of liver cancer.

The agency okayed a combination of Roche’s anti-VEGF antibody Avastin and their immunotherapy Tecentriq for patients with unresectable or metastatic hepatocellular carcinoma (HCC). The approval comes two weeks after Roche and their big biotech sub Genentech published Phase III results showing the combo improved both progression-free survival and, crucially, helped patients live longer than the long-running standard-of-care, Bayer’s Nexavar.