Alex­ion's suc­ces­sor to Soliris hits co-pri­ma­ry end­points in a piv­otal, but can't sur­pass the big block­buster

With a group of ri­vals press­ing in from every side, look­ing to cap­ture a piece of Alex­ion’s $ALXN block­buster mar­ket for the rare dis­ease trend­set­ter Soliris, re­searchers for the biotech say the first of two piv­otal stud­ies for PNH came through with non-in­fe­ri­or da­ta on their next-gen drug dubbed ALXN1210. That should leave the com­pa­ny on track for a bad­ly need­ed reg­u­la­to­ry fil­ing lat­er this year.

John Orloff

But, the parox­ys­mal noc­tur­nal he­mo­glo­bin­uria drug al­so failed a key mea­sure of su­pe­ri­or­i­ty, leav­ing Alex­ion tout­ing the sim­i­lar­i­ties of the two ther­a­pies and an eas­i­er dos­ing sched­ule that may leave quite a few sup­port­ers a wee bit dis­sat­is­fied.

The co-pri­ma­ry end­points in the study were trans­fu­sion avoid­ance and lac­tate de­hy­dro­ge­nase (LDH) nor­mal­iza­tion, stacked along­side four key sec­ondary end­points. The analy­sis on su­pe­ri­or­i­ty quick­ly broke down on the ex­am­i­na­tion of break­through he­mo­lo­y­sis: 4% of pa­tients giv­en and 10.7% for pa­tients treat­ed with Soliris. That de­liv­ered a failed p val­ue of 0.074, halt­ing the su­pe­ri­or­i­ty re­view and leav­ing some an­a­lysts a bit frus­trat­ed.

Un­der new man­age­ment af­ter CEO Lud­wig Hantson swept the old crew out, the biotech has con­cen­trat­ed heav­i­ly on ALXN1210 to save the com­pa­ny’s on­ly big fran­chise. At $542,640 a year, Soliris re­mains one of the 10 most ex­pen­sive ther­a­pies on the plan­et and Alex­ion’s cash cow.

The stock spiked on the news, pick­ing up a 9% gain mid-morn­ing as in­vestors ab­sorbed the da­ta.

Ge­of­frey Porges, Leerink

Leerink’s Ge­of­frey Porges led the cheer­ing sec­tion this morn­ing, but al­so not­ed that the tri­al fell well short of a com­plete suc­cess.

This con­sis­tent pic­ture of pos­i­tive trends in fa­vor of ALXN1210 should re­as­sure in­vestors that Alex­ion’s 2nd gen­er­a­tion prod­uct is in­deed bet­ter than Soliris; we ex­pect the stock to re­act pos­i­tive­ly to this dis­clo­sure, al­though con­tro­ver­sy will still ex­ist about whether 1210 could have shown su­pe­ri­or­i­ty in a larg­er tri­al, and whether the up­com­ing switch study could still meet the high­er hur­dle.

R&D chief John Orloff said:

Soliris has es­tab­lished a high bar for ef­fi­ca­cy. Achiev­ing non-in­fe­ri­or­i­ty on both co-pri­ma­ry and all key sec­ondary end­points, as well as see­ing nu­mer­ic re­sults in fa­vor of ALXN1210, in such a rig­or­ous study met a very high hur­dle. We look for­ward to reg­u­la­to­ry sub­mis­sions of ALXN1210 in PNH in the U.S., EU, and Japan in the sec­ond half of 2018.

Porges and al­lies be­lieve the da­ta sets up 1210 for a near cer­tain ap­proval, guard­ing the com­pa­ny’s fran­chise for many more years. But Alex­ion isn’t op­er­at­ing alone here any­more. Sev­er­al ri­vals are well along with new PNH drugs that they be­lieve can out­per­form Soliris, and now 1210.

One of those ri­vals is Apel­lis $APLS, which com­plet­ed a $150 mil­lion IPO last No­vem­ber. In 3 pa­tients nev­er treat­ed with Soliris, in­ves­ti­ga­tors re­port­ed that all of them ex­pe­ri­enced a quick cor­rec­tion on a key bio­mark­er for lac­tate de­hy­dro­ge­nase, or LDH, af­ter be­ing treat­ed with the biotech’s drug. In 6 pa­tients not re­spond­ing well to Soliris, the av­er­age he­mo­glo­bin lev­el was brought up an av­er­age of 36%, LDH was cor­rect­ed and trans­fu­sions dropped from 3.4/month on eculizum­ab monother­a­py to 0.3/month when APL-2 was added to eculizum­ab. And the biotech raised no un­usu­al red flags on the safe­ty side. Now it’s aim­ing at a piv­otal of its own.

The big ques­tion at Alex­ion re­mains open. What will Hantson do with the pipeline now? He has sought to stream­line de­vel­op­ment ef­forts and quite a few an­a­lysts are press­ing hard to make them di­ver­si­fy be­yond PNH.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

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The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

Pal­la­dio bags $20 mil­lion Se­ries B to top­ple a prob­lem­at­ic kid­ney dis­ease drug

Palladio Biosciences just took one step further in its quest to topple Otsuka’s Samsca with its own — it hopes safer — autosomal dominant polycystic kidney disease (ADPKD) drug.

The Pennsylvania-based biotech announced a $20 million Series B on Friday, which will fund a 10-person Phase III trial of its vasopressin V2 receptor agonist, lixivaptan. CEO Alex Martin expects to read out data in the first half of next year, then launch straight into a larger pivotal Phase III study with about 1,200 participants.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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