Fa­tal sep­sis at­tacks blight Acor­da’s PhI­II, trig­ger­ing new safe­ty mea­sures and tor­pe­do­ing shares

Af­ter track­ing 7 cas­es of sep­sis — with 5 deaths — in stud­ies of its late-stage Parkin­son’s drug tozadenant, Acor­da is in­creas­ing pa­tient sur­veil­lance while paus­ing en­roll­ment in its long-term safe­ty stud­ies to get a han­dle on the is­sue.

Acor­da’s shares plunged 40% on the news.

The safe­ty is­sue arose af­ter re­searchers be­came aware of the cas­es of agran­u­lo­cy­to­sis, wip­ing out the white blood cells need­ed to fight off an in­fec­tion. Now they say they will check those cell counts on a week­ly ba­sis as they study the po­ten­tial drug prob­lem with the FDA and the mon­i­tor­ing com­mit­tee.

Ron Co­hen

Acor­da CEO Ron Co­hen says they still ex­pect to re­port out Phase III safe­ty and ef­fi­ca­cy da­ta in Q1 com­ing up, but any threat to its num­ber two de­vel­op­ment pro­gram — be­hind CVT-301 — is like­ly to rat­tle its back­ers.

Leerink’s Paul Mat­teis says the sur­pris­ing news of a ma­jor safe­ty is­sue at Acor­da leaves the drug un­der a cloud.

The need for fre­quent white blood cell mon­i­tor­ing is not un­heard of for ap­proved neu­rol­o­gy prod­ucts: agran­u­lo­cy­to­sis risk is a known lim­i­ta­tion for cloza­p­ine, an ap­proved, and very ef­fec­tive atyp­i­cal an­tipsy­chot­ic. But the risk/ben­e­fit for Toz, in the con­text of an ap­par­ent mor­tal­i­ty sig­nal – and what is al­ready a crowd­ed cat­e­go­ry – is now sig­nif­i­cant­ly com­pro­mised, giv­en that the drug is not dis­ease-mod­i­fy­ing and will be tar­get­ed to­ward an al­ready frag­ile el­der­ly pop­u­la­tion.

Then, lat­er on Wednes­day, Mat­teis vir­tu­al­ly wrote it off as a los­er.

We are now very con­cerned re­gard­ing the ap­prov­abil­i­ty of Toz – even if it does work – giv­en its po­si­tion­ing as a symp­to­matic ther­a­py with a mod­er­ate lev­el of ben­e­fit. We have sig­nif­i­cant ques­tions re­gard­ing the com­mer­cial vi­a­bil­i­ty of a new symp­to­matic Parkin­son’s ther­a­py with such sig­nif­i­cant safe­ty risks.

Acor­da swooped in to buy Fin­land’s Bi­otie in ear­ly 2016 for $363 mil­lion in cash to bag the Phase III Parkin­son’s drug and add a bad­ly need­ed late-stage drug to the pipeline. Tozadenant is an oral adeno­sine A2a re­cep­tor an­tag­o­nist that’s reg­is­tered proof of con­cept da­ta for re­duc­ing “off” times among Parkin­son’s pa­tients tak­ing the stan­dard lev­odopa/car­bidopa rem­e­dy.

There’s lit­tle mar­gin for er­ror at Acor­da.

With its patents on the com­pa­ny’s cash cow Ampyra un­der at­tack, pos­si­bly open­ing the road to a gener­ic ri­val next sum­mer, the biotech has had to re-file its ap­pli­ca­tion for CVT-301. The FDA had is­sued a refuse-to-file the ap­pli­ca­tion for the drug, de­lay­ing a ther­a­py which will be need­ed to res­cue the com­pa­ny from gener­ic com­pe­ti­tion for Ampyra.

The biotech, mean­while, has moved to re­struc­ture, block a po­ten­tial hos­tile takeover at­tempt and de­flect crit­i­cism for leav­ing it­self vul­ner­a­ble to the cri­sis it’s in. If its safe­ty is­sue with tozadenant spins out of con­trol, Acor­da’s ex­ec­u­tive team will be un­der twice as much pres­sure to per­form on CVT-301.

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

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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.”

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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.

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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.

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