Aptinyx shares crater as lead drug fails in PhII neu­ro­path­ic pain study

Aptinyx’s ap­proach to mod­u­lat­ing the NM­DA re­cep­tor to treat dis­or­ders of the cen­tral ner­vous sys­tem has hit a sig­nif­i­cant snag, as its lead ex­per­i­men­tal drug failed a mid-stage study in pa­tients with di­a­bet­ic pe­riph­er­al neu­ropa­thy (DPN), oblit­er­at­ing the re­cent­ly pub­lic com­pa­ny’s stock on Wednes­day.

Nor­bert Riedel

The drug — dubbed NYX-2925 — was de­vel­oped by the Evanston, IL-based biotech that went pub­lic last Ju­ly bank­ing on its ap­proach to mod­u­late NM­DA re­cep­tors, which are cru­cial to brain and ner­vous sys­tem func­tion. The Phase II tri­al pit­ted three oral dos­es of the drug (10 mg, 50 mg, or 200 mg) ver­sus a place­bo in 300 pa­tients over four weeks. The ex­per­i­men­tal treat­ment failed to con­fer a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in av­er­age dai­ly pain — as mea­sured by a Nu­mer­i­cal Rat­ing Scale (NRS) — at week four, miss­ing the pri­ma­ry end­point of the study.

The com­pa­ny’s shares $AP­TX plum­met­ed about 70% in ear­ly trad­ing.

The com­pa­ny sug­gest­ed its 50mg dose had the most promis­ing im­pact. Pa­tients treat­ed with the dose showed a 1.61-point re­duc­tion in av­er­age dai­ly pain on the NRS — the largest de­crease among the dose lev­els eval­u­at­ed — ver­sus the 1.23-point fall in those giv­en the place­bo, re­sult­ing in a non-sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment (p=0.1586).  Pa­tients on the 50 mg dose al­so showed im­prove­ment on key sec­ondary end­points, in­clud­ing sleep and pain on walk­ing, Aptinyx added.

“While the study did not meet its pri­ma­ry end­point…we be­lieve the to­tal body of clin­i­cal da­ta in­di­cates the po­ten­tial of NYX-2925 to treat chron­ic pain,” Aptinyx chief Nor­bert Riedel said in a state­ment, adding that the com­pa­ny is now in process of find­ing a way for­ward for NYX-2925.

“It seems that at best that path for­ward may con­sist of an­oth­er phase II tri­al in DPN, us­ing the two dos­es that showed a nu­mer­i­cal dif­fer­ence to place­bo (50mg and 200mg) and in­cor­po­rat­ing longer du­ra­tion of treat­ment (8 or 12 weeks). Such a study could be­gin in H2 2019 and pro­duce a re­sult in 2020. How­ev­er, it is not clear yet whether the com­pa­ny’s board, in­ves­ti­ga­tors, ad­vi­sors and in­vestors will en­dorse the in­vest­ment in that (cost­ly) tri­al. In­vestors are like­ly to elim­i­nate all val­ue for this pro­gram from the com­pa­ny’s stock to­day and thus leave the stock re­liant up­on ear­li­er pro­grams tar­get­ing more chal­leng­ing dis­ease in­di­ca­tions in­clud­ing cog­ni­tive im­pair­ment in Parkin­son’s dis­ease (NYX-458) and post-trau­mat­ic stress dis­or­der (PTSD) (NYX-783),” Leerink’s Ge­of­frey Porges wrote in a note.

In a sep­a­rate on­go­ing ex­plorato­ry mid-stage study, NYX-2925 has shown en­cour­ag­ing re­sults in a small group of pa­tients with fi­bromyal­gia, the com­pa­ny not­ed in an in­ter­im analy­sis post­ed last month. The full re­sults of that study are ex­pect­ed in the first half of this year.

“We don’t re­gard the stock as “dead mon­ey” af­ter to­day’s news, but do rec­og­nize that a sig­nif­i­cant part of its pri­or val­u­a­tion is now im­paired. Ear­li­er this month the com­pa­ny pro­vid­ed pos­i­tive bio­mark­er da­ta for NYX-2925 in its oth­er in­di­ca­tion of fi­bromyal­gia; at this stage those bio­mark­er ef­fects are en­cour­ag­ing but in­suf­fi­cient,” Porges added.

Var­i­ous drug de­vel­op­ers are fo­cus­ing on the NM­DA re­cep­tor, de­vel­op­ing com­pounds to ac­ti­vate or in­hib­it it to treat CNS dis­or­ders, but that strat­e­gy has seen a se­ries of set­backs in part due to safe­ty con­cerns. Aptinyx be­lieves its ap­proach — with­out ever ful­ly turn­ing the re­cep­tor “on” or “off” — will al­low it to evade these chal­lenges. Al­ler­gan has bought in­to this Aptinyx phi­los­o­phy, hav­ing li­censed their de­pres­sion drug, which is now called AGN-241751. Aptinyx it­self was was spun out of Al­ler­gan’s $1.7 bil­lion buy­out of Nau­rex which CEO Brent Saun­ders want­ed for its lead NM­DA drug — now dubbed ra­pastinel — for ma­jor de­pres­sion.

In terms of pain, pa­tients have few ef­fec­tive op­tions oth­er than high­ly ad­dic­tive opi­oids, and there­fore drug de­vel­op­ers work­ing on non-opi­oid op­tions are keen­ly watched. This is like­ly one of the rea­sons the FDA grant­ed NYX-2925 fast track sta­tus for neu­ro­path­ic pain as­so­ci­at­ed with DPN.

An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Can an FDA hus­tle up on trastuzum­ab be far be­hind?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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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.

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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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Martin Shkreli [via Getty]

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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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Back in the day, decisions about which drugs and interventions were funded by the National Health Service (NHS) were made at the local level, but this ‘postcode prescribing’ system was fraught with skewed healthcare deployment making the structure unsustainable. A national system was deemed necessary — and NICE was formed to bridge that gap.

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Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

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And now they’re really going for it.

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