Alex­ion touts new PhI­II da­ta of Soliris suc­ces­sor as planned As­traZeneca takeover looms

A lit­tle less than a week be­fore As­traZeneca’s takeover of Alex­ion is ex­pect­ed to be com­plet­ed, the rare dis­ease biotech  of­fered up a cut of da­ta for its Soliris suc­ces­sor.

In a Phase III study for Ul­tomiris look­ing at adults with gen­er­al­ized myas­the­nia gravis, the drug met its pri­ma­ry end­point of sig­nif­i­cant­ly im­prov­ing scores on a pa­tient-re­port­ed as­sess­ment com­pared to place­bo af­ter 26 weeks, Alex­ion an­nounced Thurs­day af­ter­noon. Alex­ion hopes the topline re­sults rep­re­sent what could be Ul­tomiris’ third ap­proval, af­ter it notched OKs for a rare blood dis­or­der called PNH and an ul­tra-rare chron­ic dis­ease that dam­ages the kid­neys.

John Orloff

Should the FDA give Ul­tomiris the go-ahead, the drug would be avail­able for a broad­er dis­ease pop­u­la­tion than Soliris, as the old­er med­i­cine is on­ly ap­proved for those with se­vere symp­toms and com­pli­ca­tions, Alex­ion R&D chief John Orloff said in a state­ment.

The hope is to be able to treat pa­tients “with milder symp­toms or ear­li­er in their treat­ment jour­ney, while still of­fer­ing clin­i­cal­ly mean­ing­ful ben­e­fits that were seen as ear­ly as Week 1 and main­tained up to 52 weeks,” Orloff said.

Gen­er­al­ized myas­the­nia gravis is a rare au­toim­mune dis­or­der caused by in­flam­ma­tion that dam­ages the con­nec­tion point be­tween nerve cells and mus­cles. The dam­age leads to a “break­down in com­mu­ni­ca­tion” be­tween the brain and mus­cles, Alex­ion said, caus­ing loss of mus­cle func­tion and se­vere weak­ness. It can oc­cur at any age, but be­gins most com­mon­ly for women un­der 40 and men over 60.

Alex­ion en­rolled 175 in­di­vid­u­als in the Phase III study who were ran­dom­ized 1-to-1. Pa­tients in the drug arm re­ceived a “weight-based load­ing dose” on day 1, fol­lowed two weeks lat­er by a main­te­nance dose. Sub­se­quent dos­ing took place every eight weeks af­ter that un­til the study was com­plet­ed.

The pri­ma­ry end­point, a pa­tient-re­port­ed test on dai­ly liv­ing, showed those tak­ing the drug saw av­er­age scores -1.6 points be­low base­line com­pared to place­bo, good for a sparkling p-val­ue of p<0.001. Some sec­ondary end­points al­so reached sta­tis­ti­cal sig­nif­i­cance, in­clud­ing a clin­i­cian as­sess­ment of sever­i­ty (p<0.001) and to­tal num­ber of pa­tients reach­ing at least 5 points of im­prove­ment in that score rel­a­tive to the con­trol (p=0.005).

Oth­er sec­ondary goals look­ing at qual­i­ty of life, how­ev­er, did not reach the mag­ic p=0.05 num­ber. One rat­ing scale ex­am­in­ing qual­i­ty of life just bare­ly missed with a p=val­ue of p=0.064, while an­oth­er mea­sur­ing fa­tigue whiffed bad­ly, com­ing in at p=0.373.

Alex­ion said side ef­fects were com­pa­ra­ble be­tween the two groups, with the most com­mon­ly re­port­ed event of headache oc­cur­ring more fre­quent­ly in the place­bo arm. Di­ar­rhea and nau­sea were the next most com­mon side ef­fects. Se­ri­ous ad­verse events such as myas­the­nia gravis cri­sis were ob­served in 1.2% of pa­tients in the drug arm, while more pa­tients saw dis­ease wors­en­ing in the place­bo group at 3.4%.

An open-la­bel ex­ten­sion pe­ri­od of an ad­di­tion­al 26 weeks showed an­oth­er 75 pa­tients from the drug arm main­tain­ing their dis­ease, Alex­ion added.

The topline re­sults re­leased Thurs­day could bring good tid­ings to Alex­ion’s new part­ners at As­traZeneca, where the biotech is ex­pect­ed to be­come the com­pa­ny’s en­tire rare dis­ease unit. In ad­di­tion to Soliris, which pulled in more than $4 bil­lion in sales last year, Ul­tomiris will like­ly play a key role in As­traZeneca’s sta­ble of drugs. Alex­ion has po­si­tioned Ul­tomiris to soak up most of the old­er drug’s sales, de­spite fac­ing new com­pe­ti­tion from Apel­lis’ Em­paveli.

As­traZeneca’s planned $39 bil­lion ac­qui­si­tion cleared its fi­nal reg­u­la­to­ry hur­dle ear­li­er this week, when the UK’s fi­nan­cial watch­dog gave the deal the thumbs-up. The trans­ac­tion is ex­pect­ed to close on Ju­ly 21, with Alex­ion shares $ALXN be­ing con­vert­ed to As­traZeneca stock $AZN and re­moved from Nas­daq trad­ing the next day.

Adap­tive De­sign Meth­ods Of­fer Rapid, Seam­less Tran­si­tion Be­tween Study Phas­es in Rare Can­cer Tri­als

Rare cancers account for 22 percent of cancer diagnoses worldwide, yet there is no universally accepted definition for a “rare” cancer. Moreover, with the evolution of genomics and associated changes in categorizing tumors, some common cancers are now characterized into groups of rare cancers, each with a unique implication for patient management and therapy.

Adaptive designs, which allow for prospectively planned modifications to study design based on accumulating data from subjects in the trial, can be used to optimize rare oncology trials (see Figure 1). Adaptive design studies may include multiple cohorts and multiple tumor types. In addition, numerous adaptation methods may be used in a single trial and may facilitate a more rapid, seamless transition between study phases.

Matt Gline (L) and Pete Salzmann

UP­DAT­ED: Roivant bumps stake in Im­muno­vant with a $200M deal. But with M&A off the ta­ble, shares crater

Roivant has worked out a deal to pick up a chunk of stock in its majority-owned sub Immunovant $IMVT, but the stock buy falls far short of its much-discussed thoughts about buying out all of the 43% of shares it doesn’t already own.

Roivant, which recently inked a SPAC move to the market at a $7 billion-plus valuation, has forged a deal to boost its ownership in Immunovant by 6.3 points, ending with 63.8% of the biotech’s stock following a $200 million injection. That cash will bolster Immunovant’s cash reserves, giving it a $600 million war chest to fund a slate of late-stage studies for its big drug: the anti-FcRn antibody IMVT-1401.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Sanofi preps a multi­bil­lion-dol­lar buy­out of an mR­NA pi­o­neer af­ter falling be­hind in the race for a Covid-19 jab — re­port

It looks like Sanofi CEO Paul Hudson is dead serious about his intention to vault directly into contention for the future of mRNA vaccines.

A year after paying Translate Bio a whopping $425 million in an upfront and equity payment to help guide the pharma giant to the promised land of mRNA vaccines for Covid-19, Sanofi is reportedly ready to close the deal with a buyout.

Translate’s stock $TBIO soared 78% after the market closed Monday. A spokesperson for Sanofi declined to comment on the report, telling Endpoints News that the company doesn’t comment on market rumors.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Alan Hirzel, Abcam

Drug sup­pli­er Ab­cam brings a long­time col­lab­o­ra­tor in house as part of $340M buy­out pact

BioVision has supplied Abcam with research tools since 1999, and now the two are making it official as part of a merger unveiled Monday.

Abcam will buyout BioVision as part of a $340 million acquisition deal to bring aboard the supplier’s biochemical and cell-based assays for biological research, as well as recombinant proteins, antibodies and enzymes.

The deal will give Abcam control of BioVision’s portfolio and allow for both the expansion of research existing areas of focus such as oncology, neuroscience and epigenetics and preparation to expand into new products. As a part of the deal, Abcam will develop and supply products and services to NKY, the previous owner of BioVision and receive support for ongoing development and commercialization of in vitro diagnostic products.

Tib­so­vo clears an­oth­er hur­dle for Servi­er, but can it make Agios' old drug prof­itable?

When European regulators saw the data Agios used to win US approval for their AML drug Tibsovo, they sent the more than decade-old biotech back to the drawing board. A single, single-armed trial was not going to cut it.

On Monday, though, the drug’s new owners announced it had cleared a more rigorous study. In a randomized, Phase III trial of certain newly diagnosed patients, those who received a combination of Tibsovo and chemotherapy lived longer than those who received a combination of placebo and chemotherapy. Those patients also had higher response rates and complete remission rates.

UP­DAT­ED: Watch out Glax­o­SmithK­line: As­traZeneca's once-failed lu­pus drug is now ap­proved

Capping a roller coaster journey, AstraZeneca has steered its lupus drug anifrolumab across the finish line.

Saphnelo, as the antibody will be marketed, is the only treatment that’s been approved for systemic lupus erythematosus since GlaxoSmithKline’s Benlysta clinched an OK in 2011. The British drugmaker notes it’s also the first to target the type I interferon receptor.

Mirroring the population that the drug was tested on in late-stage trials, regulators sanctioned it for patients with moderate to severe cases who are already receiving standard therapy — setting up a launch planned for the end of August, according to Ruud Dobber, who’s in charge of AstraZeneca’s biopharmaceuticals business unit.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Not all mR­NA vac­cines are cre­at­ed equal. Does it mat­ter?; Neu­ro is back; Pri­vate M&A af­fair; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As part of our broader and deeper drive, Endpoints has been pairing webinars with our special reports to cover more angles on a given topic. In conjunction with Max Gelman’s neuroscience feature, Kyle Blankenship moderated an insightful panel to discuss where the field is headed. You can register to watch it on demand here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 113,300+ biopharma pros reading Endpoints daily — and it's free.

Bris­tol My­ers pulls lym­phoma in­di­ca­tion for Is­to­dax af­ter con­fir­ma­to­ry tri­al falls flat

Amid an industrywide review of cancer drugs with accelerated approval, Bristol Myers Squibb had to make the tough call last month to yank an approval for leading I/O drug Opdivo after flopping a confirmatory study. Now, a second Bristol Myers drug is on the chopping block.

Bristol Myers has pulled aging HDAC inhibitor Istodax’s indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint, the drugmaker said Monday.

Rick Pazdur (via AACR)

FDA's on­col­o­gy head Rick Paz­dur de­fends the ac­cel­er­at­ed ap­proval path­way, claim­ing it is 'un­der at­tack'

The FDA is sounding the alarm over its accelerated approval pathway as backlash continues over the recent nod in favor of Biogen’s Alzheimer’s drug Aduhelm, and an ODAC meeting on six such approvals that could potentially be pulled from the market — two of which already have.

“Do you think accelerated approval is under attack? I do,” Rick Pazdur, head of FDA’s Oncology Center of Excellence, said at a Friends of Cancer Research webinar on Thursday.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.