Newron's Mer­ck KGaA-in li­censed com­pound fails Rett Syn­drome study, shares wilt

Mu­ta­tions in a gene called MECP2 were iden­ti­fied as the cause of Rett Syn­drome in 1999 in­side a lab­o­ra­to­ry at the Bay­lor Col­lege of Med­i­cine — the same year, Ital­ian drug de­vel­op­er Newron Phar­ma­ceu­ti­cals was born. On Mon­day, the com­pa­ny’s ex­per­i­men­tal drug, sari­zotan, failed a Phase II/III study in pa­tients with the se­vere neu­rode­vel­op­men­tal dis­or­der that has no ap­proved ther­a­pies.

In-li­censed from Mer­ck KGaA, the com­pound is de­signed to mod­u­late the ac­tiv­i­ty of neu­ro­trans­mit­ters and was aban­doned by the Ger­man drug­mak­er in 2006 af­ter a pair of failed piv­otal stud­ies in Parkin­son’s dis­ease. Now, Newron is al­so ter­mi­nat­ing its de­vel­op­men­tal pro­gram in Rett syn­drome.

The tri­al test­ed two dos­es of sari­zotan (10 mg and 20 mg) against a place­bo in 129 pa­tients with the dis­ease that al­most ex­clu­sive­ly af­fects fe­males, and is char­ac­ter­ized by a loss of ac­quired fine and gross mo­tor skills as well as neu­ro­log­i­cal, cog­ni­tive and au­to­nom­ic dys­func­tion, which leads to loss of abil­i­ty to con­duct dai­ly life ac­tiv­i­ties, walk or com­mu­ni­cate.

The main goal of the study — to in­duce a re­duc­tion in episodes of ap­nea dur­ing wak­ing time com­pared with place­bo — was not met, nei­ther were any sec­ondary goals. De­tailed da­ta will be pre­sent­ed at a lat­er date, Newron said.

Ravi Anand, Newron

“The re­sults of this well de­signed and ex­e­cut­ed study, based on high­ly promis­ing da­ta from a ge­net­ic mod­el of Rett syn­drome in mice, in­di­cate the dif­fi­cul­ties in­her­ent in trans­lat­ing ef­fects in an­i­mal mod­els to hu­man clin­i­cal stud­ies,” the com­pa­ny’s CMO Ravi Anand said in a state­ment.

The com­pa­ny’s shares cratered more than 68% on the Swiss stock ex­change to CHF 1.98.

“This high-risk pro­gramme was a key fo­cus for the stock, with sari­zotan un­der­pin­ning c.70% of our CHF40/share PT (price tar­get),” Jef­feries an­a­lysts wrote in a note.

New York biotech Anavex is an­oth­er com­pa­ny eval­u­at­ing its lead ex­per­i­men­tal drug, blar­came­sine, in pa­tients with Rett Syn­drome — in Feb­ru­ary, the FDA grant­ed the drug fast track sta­tus for the in­di­ca­tion. Aca­dia Phar­ma­ceu­ti­cals, the mak­er of the Parkin­son’s dis­ease drug Nu­plazid, has an ex­per­i­men­tal Rett syn­drome drug in late-stage de­vel­op­ment. GW Phar­ma, the first-ever com­pa­ny to get a nat­ur­al cannabis-de­rived ther­a­py ap­proved by the FDA, al­so has a CBD drug-in-de­vel­op­ment for Rett, while the cat tran­quil­iz­er ke­t­a­mine is al­so be­ing eval­u­at­ed by an aca­d­e­m­ic group for the con­di­tion.

Newron, mean­while, is now left with two eggs in its bas­ket. It gets roy­al­ty in­come from its Parkin­son’s dis­ease drug, Xada­go, which is sold by its part­ners in dif­fer­ent parts of the world. The oth­er drug in the com­pa­ny’s pipeline, eve­namide, is be­ing de­vel­oped for schiz­o­phre­nia, al­though Covid-19 has de­layed late-stage en­abling tri­als.

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.