Pumped by an ear­ly glimpse of ef­fi­ca­cy, Newron charts a piv­otal course for schiz­o­phre­nia drug

Ravi Anand, Newron

Just a few days af­ter Newron fi­nal­ly land­ed an FDA ap­proval for Parkin­son’s add-on ther­a­py Xada­go af­ter a 4-year reg­u­la­to­ry odyssey, the biotech is back with a snap­shot of ear­ly da­ta on a new treat­ment for schiz­o­phre­nia. And while they were able to pull out pos­i­tive da­ta from the Phase IIa study of eve­namide, in­ves­ti­ga­tors plan to make some sig­nif­i­cant changes to the next study that could pro­vide more plain­ly promis­ing piv­otal re­sults.

Pre­sent­ing at the 16th Con­gress on Schiz­o­phre­nia Re­search in San Diego over the week­end, Newron con­clud­ed that their drug eve­namide did help a large group of pa­tients.

The mean change for the Pos­i­tive and Neg­a­tive Syn­drome Scale (PANSS) score over­all was -5.1 for the add-on com­pared to -3.7 for the place­bo, which Newron Chief Med­ical Of­fi­cer Ravi Anand de­scribed as “very close” to sta­tis­ti­cal sig­nif­i­cance. If you just looked at the pos­i­tive side of the scale, he added, the re­sults were sta­tis­ti­cal­ly sig­nif­i­cant.

It’s im­por­tant to note that Newron and Anand de­cid­ed to amp up the study so they could go be­yond the safe­ty da­ta they were orig­i­nal­ly look­ing for — the drug proved tol­er­a­ble, they say — and start to see how this ther­a­py could work as an add-on.

The com­pa­ny re­cruit­ed 89 schiz­o­phre­nia pa­tients with break­through psy­chot­ic symp­toms while be­ing treat­ed with risperi­done or arip­ipra­zole.

“Com­pound A or B have the same char­ac­ter­is­tics,” says Anand. “All of them work to a cer­tain ex­tent.”

The two main ther­a­pies in use for schiz­o­phre­nia do es­sen­tial­ly the same thing, Anand tells me. And the re­sults are fre­quent­ly the same as well. Pa­tients of­ten re­spond ini­tial­ly and then switch af­ter the re­sponse winds down. And then the re­sponse winds down again.

In a wide range of an­i­mal tests, he adds, eve­namide ap­peared lim­it­ed to sodi­um chan­nel block­age and glu­ta­mate re­lease, which is what they were look­ing for as a sign of its on-tar­get speci­fici­ty, re­duc­ing the odds of an off-tar­get hit.

While the place­bo re­sponse may look large to the unini­ti­at­ed, Anand says it’s ac­tu­al­ly low. That’s be­cause re­searchers specif­i­cal­ly looked for pa­tients with a con­strained lev­el of symp­toms. In the piv­otal tri­als to come, he says, they’ll be look­ing for pa­tients ex­pe­ri­enc­ing el­e­vat­ed symp­toms of schiz­o­phre­nia, where the drug’s im­pact could be more clear­ly dis­tin­guished from a place­bo. And if it works in the next tri­al in­volv­ing about 360 pa­tients, to get start­ed next year, he be­lieves it will be straight­for­ward to repli­cate the re­sults in a sec­ond con­fir­ma­to­ry tri­al re­quired by the FDA.

Anand adds that the drug’s “ef­fect ap­pears much bet­ter in younger pa­tients.” That’s be­cause “old­er pa­tients have lost the ca­pac­i­ty to re­spond. The dis­ease de­stroys cog­ni­tion” and as pa­tients age, there are neu­ro­chem­i­cal changes in the brain due to their long run­ning use of an­ti-psy­chotics that make their re­sponse to an add-on like eve­namide less like­ly.

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

Bi­cy­cle Ther­a­peu­tics takes Roche's Genen­tech on an up to $2B im­muno-on­col­o­gy ride

Bicycle Therapeutics — which is developing a new class of chemically synthesized drugs designed to be pharmacologically as active as biologics, yet manufactured as small molecules —  has scored another big partner: Roche’s Genentech.

The transatlantic biotech, which was created in 2009 and made its public debut a decade later, gets $30 million upfront and a meaty $1.7 billion in potential milestone payments in an early discovery immuno-oncology collaboration with Genentech.

When drug val­ue as­sess­ment meets re­al-world ev­i­dence: ICER en­lists Ae­tion in pric­ing eval­u­a­tion

In a union of two of the hottest trends in the US biopharma world, ICER is teaming up with a high-profile company to integrate real-world evidence in their assessment of treatment value.

The drug pricing watchdog — formally the Institute for Clinical and Economic Review — said it will utilize Aetion’s evidence platform in “select upcoming assessments” and their new 24-month re-evaluations of drugs granted accelerated approval by the FDA.

First US Covid-19 tri­als set to get un­der­way in Ne­bras­ka and Wash­ing­ton, backed by NIH

The first US clinical trials on the novel coronavirus are scheduled to get underway next month at the University of Nebraska Medical Center, where American passengers were taken after being evacuated from the Diamond Princess cruise ship, and at the Kaiser Permanente Washington Health Research Institute. Both trials are sponsored by the NIH’s National Institute for Allergy and Infectious Diseases, which has led the US’s medical response to the outbreak.

Anthony Fauci (AP Images)

UP­DAT­ED: NIH-part­nered Mod­er­na ships off its PhI-ready coro­n­avirus vac­cine can­di­date to a sea of un­cer­tain­ty

Off it goes.

Moderna has shipped the first batch of its mRNA vaccine against SARS-CoV-2 from its manufacturing facility in Norwood, Massachusetts, to the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, for a pioneering Phase I study.

It’s a hectic race against time. In the 42 days since Moderna selected the sequence they would use to develop their vaccine — a record time, no less — the number of confirmed cases around the world has surged astronomically from a few dozen to over 80,000, per WHO and Johns Hopkins estimates.

The candidate that they came up with, mRNA-1273, encodes for a prefusion stabilized form of the spike protein, which gives the virus its crown shape and plays a key role in transmission. The Coalition for Epidemic Preparedness Innovations, the Oslo-based group better known as CEPI, funded the manufacture of this batch.

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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.

Mallinck­rodt, once the na­tion’s largest oxy­codone pro­duc­er, an­nounces ten­ta­tive $1.6B set­tle­ment

Three years after it first paid out fines for its role in the US opioid abuse epidemic, Mallinckrodt has announced an agreement-in-principle that will see the company pay out $1.6 billion and place its generics unit in bankruptcy.

The tentative deal would settle hundreds of lawsuits from state and local governments over Mallinckrodt’s role in the epidemic, while also helping address the company’s increasingly mountainous debt. Although Purdue Pharma has drawn the bulk of both public and legal acrimony for opioid sales, documents made public earlier this year showed that Mallinckrodt subsidiary SpecGx, along with the generic subsidiaries of Teva and Endo Pharmaceuticals, accounted for the vast majority of the 76 billion opioid pills distributed from 2006 to 2012. Mallinckrodt was at the top of that list.

FDA launch­es search­able Pur­ple Book

The FDA on Monday unveiled the first version of its searchable online database of biological product information, known as the Purple Book.

Building off the previous PDF lists of biological products, the database now allows for easier searches and includes information on product names (proprietary and proper), the type of biologics license application (BLA) that was submitted, strength of the biologic, dosage form, product presentation, license status, BLA number and approval date.

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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