Min­er­va claims 'pos­i­tive' PhII da­ta on de­pres­sion drug while skep­tics push stock down

It might have come in a bit of an un­ortho­dox shape, but Min­er­va Neu­ro­sciences says it has a Phase II win in its hands.

When mea­sured against the bar of a 2-sided type I er­ror lev­el of 0.1, the biotech said, one of three test­ed dos­es of its de­pres­sion drug sel­torex­ant pass­es muster for a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment over place­bo. In their words:

The least squares mean (LS mean) dif­fer­ence from place­bo of the change in [Mont­gomery-As­berg De­pres­sion Rat­ing Scale] to­tal score at the end of week 6 was 3.1 for the 20 mg dose of sel­torex­ant, and the 2-sided p-val­ue was 0.083, which is be­low the pre-spec­i­fied 2-sided type I er­ror lev­el of 0.1.

Re­my Luthringer

The 20mg dose is the on­ly arm that Min­er­va was pre­pared to re­port on. In­ves­ti­ga­tors halt­ed en­roll­ment in the 40 mg group ear­li­er, while the 10 mg arm had too few pa­tients to be in­for­ma­tive.

That sounds like cher­ry pick­ing for some in­vestors, send­ing shares $NERV down 7% to $6.42.

Jef­feries an­a­lysts, on the oth­er hand, en­dorsed the rosy view: “We think con­fu­sion on ef­fi­ca­cy da­ta caused the ini­tial stock re­ac­tion, how­ev­er, the da­ta sug­gests a path for­ward w/ PI­II start­ing ear­ly ’20.”

In the tri­al, the oral pill was giv­en to adult pa­tients with ma­jor de­pres­sive dis­or­der along­side stan­dard an­ti­de­pres­sant ther­a­pies, in­clud­ing sero­tonin re­up­take in­hibitors (SS­RIs) and sero­tonin-nor­ep­i­neph­rine re­up­take in­hibitors (SNRIs), to which they have not re­spond­ed ad­e­quate­ly.

Min­er­va want­ed to boost the re­sponse rates (on­ly 30% to 40% by its count) by tin­ker­ing with the orex­in sys­tem, which is as­so­ci­at­ed with feed­ing, home­osta­sis, arousal, mod­u­la­tion of sleep-wake cy­cles and mo­ti­va­tion. Janssen signed on as a part­ner to sel­torex­ant, an ORX2 in­hibitor, on two in­di­ca­tions in 2014, but re­turned the rights for in­som­nia three years lat­er.

The amend­ed deal left Min­er­va sole­ly in charge of de­vel­op­ing sel­torex­ant as an in­som­nia treat­ment. It took the op­por­tu­ni­ty to high­light the con­nec­tion be­tween the two con­di­tions by sin­gling out one of 19 sec­ondary analy­ses: a sub­group with clin­i­cal­ly sig­nif­i­cant in­som­nia. Those pa­tients, who strug­gle to sleep, saw an LS mean dif­fer­ence ver­sus place­bo of 4.9 on the MADRS score with a 2-sided p-val­ue of 0.050.

Ac­cord­ing to the Jef­feries note, around 105 pa­tients be­tween the drug and place­bo arms be­longed in that group.

“While the 3.1 point dif­fer­ence in the over­all pop­u­la­tion does not ap­pear to dif­fer­en­ti­ate from oth­er an­ti­de­pres­sants ap­proved for ad­junc­tive use (2.8 point dif­fer­ence from pbo ob­served on avg), the 4.9 point dif­fer­ence in the pts with sig­nif­i­cant in­som­nia ap­pears clin­i­cal­ly mean­ing­ful,” the an­a­lysts wrote.

A sep­a­rate Phase IIb tri­al for in­som­nia has com­plet­ed en­roll­ment, CEO Re­my Luthringer added with topline re­sults ex­pect­ed lat­er this quar­ter.

Im­age: Shut­ter­stock

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology

ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development

CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources.