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.

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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An NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

'Xeno­trans­plan­ta­tion is com­ing': New NE­JM pa­per gives de­tailed look in­to 2 pig-to-hu­man kid­ney trans­plant cas­es

The thymokidney is a curious organ, if you could call it that. It’s a sort of Frankensteinian creation — a system of pig thymus embedded underneath the outer layer of a pig’s kidney, made for human transplantation.

In the first case of pig-to-human xenotransplantation of a kidney into a brain-dead patient, the thymokidney quietly featured front and center.

In that experiment, which took place in September of last year, NYU researchers led by Robert Montgomery sutured a pig thymokidney onto the leg of a brain-dead 66-year-old woman. That case was widely reported on by a horde of major media outlets, including the New York Times, the BBC, and an in-depth feature by USA Today.

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Vlad Coric, Biohaven CEO

UP­DAT­ED: Fresh off $11.6B sale to Pfiz­er, New Bio­haven hits Phase III set­back just weeks af­ter Vlad Coric chalked up promise

When Pfizer bought up Biohaven’s migraine portfolio in the largest M&A deal of the year earlier this month, Biohaven CEO Vlad Coric promised the rest of the pipeline, which will live on under the umbrella of New Biohaven, still has a lot to offer. But that vision took a dent Monday as the drugmaker revealed it’s once again flopped on troriluzole.

The glutamate regulator failed to meet the primary endpoint on a Phase III study in patients with spinocerebellar ataxia, an inherited disorder that impairs a person’s ability to walk, speak and swallow. SCA can also lead to premature death.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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(Credit: Shutterstock)

Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Saqib Islam, SpringWorks CEO

Pfiz­er spin­out Spring­Works will ship its first drug to the FDA be­fore year’s end with PhI­II win

SpringWorks Therapeutics thinks it has cemented the backbone for its first “pipeline-in-a-product” oncology treatment and will send it to the FDA before the clock strikes 2023 with a Phase III win on Tuesday.

The oral gamma secretase inhibitor, dubbed nirogacestat, beat placebo on the primary goal of progression-free survival in adults with progressing desmoid tumors.

The soft-tissue tumors can lead to long-lasting pain, disfigurement and amputation, and there are currently no approved meds for the rare oncology indication. The tumors typically impact patients aged 20 to 44 years old and disproportionately affect women at rates 2 to 3 times higher, with up to a total of 1,650 new cases diagnosed in the US annually, according to SpringWorks.

Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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