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.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115 mil­lion and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS–CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.