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.”

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.

FDA asks why No­var­tis took two months to launch for­mal in­ter­nal probe, af­ter AveX­is flagged da­ta ma­nip­u­la­tion

And the plot thickens. Novartis $NVS officials are reportedly now scrambling to explain to the FDA why it took them two months to open an internal investigation into data discrepancies for their $2.1 million gene-therapy for spinal muscular dystrophy — the world’s most expensive drug.

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Build­ing on suc­cess­ful PD-1 pact, Eli Lil­ly li­cens­es di­a­betes drug to Chi­nese part­ners at In­novent

Eli Lilly is expanding its partnership with China’s Innovent in a deal involving a diabetes drug sitting in its Phase I reserves.

The two companies had jointly developed one of China’s first homegrown PD-1 agents, scoring an approval for Tyvyt (sintilimab) late last year for relapsed/refractory classical Hodgkin’s lymphoma. This time around, Lilly is out-licensing a piece of its diabetes pipeline, a leading franchise that has historically produced the top-selling Trulicity and Humalog.

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.