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.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; 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.

The slate of products we’re offering here at Endpoints is continuing to grow, and it’s not just limited to editorial. If you haven’t, do visit your reader profile to see if there are any other weekly newsletters you’re interested in — as each comes with its own exclusive content. And don’t miss the publisher’s note from Arsalan Arif on Endpoints Studio, our latest avenue for advertising on Endpoints.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.

Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.

Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Vas Narasimhan, Novartis CEO (Thibault Camus/Pool via AP Images)

With gener­ic com­pe­ti­tion heat­ing up, Vas Narasimhan out­lines No­var­tis' growth plans at R&D day

Thursday marks Novartis’ annual R&D day, and with it comes CEO Vas Narasimhan’s attempt to spotlight the company’s pipeline strategy and emerging stars.

The biggest question entering Thursday’s presentation dealt with how the big biopharma will make up revenues from upcoming generic competition — Novartis says within the next five years, generics will eat away roughly $9 billion in sales. To offset this, Narasimhan outlined a strategy for 4% growth or higher until 2026, focusing on six key medicines he believes will see multibillion dollar profits during this time.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 124,600+ biopharma pros reading Endpoints daily — and it's free.