Fu­til­i­ty analy­sis au­gurs de­feat in piv­otal tri­al test­ing of Nu­Cana's lead drug in metasta­t­ic pan­cre­at­ic can­cer

Near­ly two years af­ter mak­ing its pub­lic de­but, UK-based Nu­Cana’s mis­sion to make chemother­a­pies more po­tent and safer was dealt a blow, af­ter a piv­otal study test­ing its lead ex­per­i­men­tal drug halt­ed en­roll­ment in a hard-to-treat ad­vanced form of can­cer, fol­low­ing a fu­til­i­ty analy­sis.

The drug, Ace­lar­in, is be­ing eval­u­at­ed for use in metasta­t­ic pan­cre­at­ic can­cer pa­tients who were not con­sid­ered suit­able for com­bi­na­tion chemother­a­py. In the late-stage ACE­LARATE study — which com­pared the ex­per­i­men­tal drug against the chemother­a­py gem­c­itabine — 200 pa­tients had been en­rolled by the spon­sor, Clat­ter­bridge Can­cer Cen­tre, be­fore an analy­sis from an in­de­pen­dent safe­ty and da­ta mon­i­tor­ing pan­el sug­gest­ed the study’s main goal would not be met.

Nu­Cana’s Pro-Tides tech­nol­o­gy — which emerged out of a Cardiff Uni­ver­si­ty lab­o­ra­to­ry led by the com­pa­ny’s late chief sci­en­tif­ic of­fi­cer, Christo­pher McGuigan, is de­signed to su­per­charge chemother­a­py —specif­i­cal­ly nu­cle­o­side analogs (mol­e­cules that mim­ic the struc­ture of com­po­nents of nu­cle­ic acids, but are de­signed to in­ter­rupt the repli­ca­tion of ge­net­ic ma­te­r­i­al and there­by cause can­cer cell death). The tech­nol­o­gy is en­gi­neered to im­prove the ef­fi­ca­cy of these chemother­a­peu­tic agents by cur­tail­ing the re­sis­tance put up by can­cer cells and op­ti­miz­ing their side-ef­fect pro­file by di­min­ish­ing the tox­i­c­i­ty they typ­i­cal­ly bran­dish.

In the case of Ace­lar­in — a pur­port­ed gem­c­itabine up­grade — the Pro­Tide’s chem­i­cal struc­ture is de­signed to en­able its en­try in­to the can­cer cell in­de­pen­dent of mem­brane trans­porters and pro­tect­ing it from both ex­tra­cel­lu­lar and in­tra­cel­lu­lar degra­da­tion, there­by en­hanc­ing its po­ten­cy.

The pri­ma­ry end­point of the tri­al was to achieve at least a 42% re­duc­tion in risk of death com­pared to gem­c­itabine. Af­ter re­view­ing the analy­sis, the spon­sor de­cid­ed to sus­pend study re­cruit­ment — but al­low the 25 pa­tients who are see­ing some ben­e­fit to con­tin­ue with the drug.

Daniel Palmer Clat­ter­bridge Can­cer Cen­tre

“There were im­bal­ances in un­fa­vor­able prog­nos­tic fac­tors for the pa­tients in the Ace­lar­in arm which may have im­pact­ed the fu­til­i­ty analy­sis. In par­tic­u­lar, 54% of the pa­tients in the Ace­lar­in arm were di­ag­nosed at the most ad­vanced stage T4, com­pared to 36% of pa­tients in the gem­c­itabine arm,” Daniel Palmer, the tri­al’s chief in­ves­ti­ga­tor, said on Tues­day. “We need to al­low the da­ta to ma­ture and con­duct ad­di­tion­al analy­ses, in­clud­ing bio­mark­er as­sess­ment, in or­der to de­ter­mine the most ap­pro­pri­ate course of ac­tion.”

Cor­rect­ing for such vari­able fac­tors, the com­pa­ny has as­sert­ed it is see­ing pos­i­tive sur­vival trends for Acler­arin (ver­sus gem­c­itabine) in the dif­fi­cult-to-treat pop­u­la­tion, al­though the da­ta is not yet ma­ture enough to be quan­ti­fied. These num­bers can be ex­pect­ed in the first quar­ter of next year, Jef­feries an­a­lyst Eun Yang wrote in a note.

The drug is al­so be­ing test­ed in both plat­inum-re­sis­tant and plat­inum-sen­si­tive ovar­i­an can­cer as well as a first-line treat­ment in bil­iary can­cer, for which there are no ap­proved treat­ments.

Though pan­cre­at­ic can­cer “ac­count­ed for a third of our val­u­a­tion giv­en its most ad­vanced stage, key val­ue dri­vers are chemo com­bo with Ace­lar­in in bil­iary can­cer (Ph3) & NUC-3373 in col­orec­tal can­cer (Ph1 ef­fi­ca­cy da­ta in 2020),” Yang wrote in a note en­ti­tled “Clin­i­cal Set­back for Ace­lar­in, but Com­bo Ther­a­py & Pipeline Po­ten­tial Re­main.”

Shares of Nu­Cana $NC­NA tum­bled more than 20% on Tues­day af­ter the an­nounce­ment but pared some of those loss­es in Wednes­day pre­mar­ket trad­ing. The stock was up about 3% at 7.55 be­fore the bell. In Sep­tem­ber 2017, the com­pa­ny went pub­lic at $15/share. The much-ma­ligned Wood­ford In­vest­ment Man­age­ment, which sus­pend­ed fund re­demp­tions ear­li­er this year, is one of Nu­Cana‘s largest share­hold­ers own­ing a 10% stake.

So­cial im­age: Shut­ter­stock

Scott Gottlieb, AP Images

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Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

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Bright and early European time Monday morning the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation of a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month. In a followup call, Dunsire also noted that the company will likely need 200 to 250 reps for this marketing task on both sides of the Atlantic. And analysts were quick to note that the dealmaking at Lundbeck isn’t done, with another $2 billion to $3 billion available for more deals to beef up the pipeline.

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Warts for the win: Aclar­is' lead drug clears piv­otal study

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The company — which earlier this month decided to focus on its arsenal of kinase inhibitors — on Monday unveiled positive data from a pivotal study testing its lead experimental drug for use in common warts.

The drug, A-101, was tested in a 502-patient study called THWART-2 — patients enrolled had one to six warts before qualifying for the trial. Patients either self-administered A-101 topical solution or a vehicle twice a week over a two-month period. A higher proportion of patients on the drug (a potent hydrogen peroxide topical solution) saw their warts disappear at day 60, versus the vehicle (p<0.0001) — meeting the main goal of the study.  Each secondary endpoint also emerged in favor of A-101, the company said.

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Gone is the ACE-083 project in patients with facioscapulohumeral muscular dystrophy. Their drug hit the primary endpoint on building muscle but flopped on key secondaries for functional improvements in patients, which execs felt was vital to the drug’s success.