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

Andre Kalil, AP Images

A 9/11-era Om­a­ha fa­cil­i­ty, an old Ebo­la drug, and the ubiq­ui­tous Dr. Fau­ci: In­side the first US nov­el coro­n­avirus tri­al

The first 11 coronavirus patients who arrived in Omaha last week, airlifted across the globe after two weeks quarantined on a cruise ship, showed only minor symptoms or none at all. And then one of them — or one of the couple of Americans who arrived later — got worse. He developed pneumonia, a life-threatening complication for coronavirus patients.

In a biocontainment room at the University of Nebraska Medical Center on Friday, doctors infused him with an experimental Gilead drug once developed for Ebola, called remdesivir. Or they gave him a placebo. For the first time in the US, neither he nor the doctors knew.

The first US novel coronavirus trial was underway and with it, a mad dash for an answer. Sponsored by the NIH, the study marked a critical point in the epidemic. Since the start of the outbreak, the agency had helped lead a global effort to contain the virus. Now, as it spread worldwide and the CDC issued warnings the US could see a major internal outbreak, they were looking at home.

“We don’t have too much time,” Andre Kalil, the trial’s lead investigator, told Endpoints News. “Everything’s moving really fast.”

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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

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Dan O'Day (AP Images)

A name emerges out of the Gilead M&A ru­mor mill, and it’s a can­cer biotech

After months of questions and speculation about when and if Gilead will make a major acquisitions, a name has emerged.

The California-based drugmaker has approached Forty Seven Inc, a cancer biotech, with a takeover offer, Bloomberg News reports. With Forty Seven’s market cap at $2.3 billion, an acquisition would likely be Gilead’s largest since they acquired Kite Pharma for $11.9 billion in 2017.

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Biogen head of R&D Al Sandrock, Sangamo CEO Sandy Macrae

UP­DAT­ED: Bio­gen makes an­oth­er bold Alzheimer’s bet, drop­ping $350M up­front to part­ner with genome-edit­ing fo­cused Sang­amo

While the fate of Biogen’s resurrected Alzheimer’s drug aducanumab remains uncertain, the Cambridge, MA-based drugmaker is joining forces with genome editing company Sangamo Therapeutics to develop therapies for neurological conditions.

Sangamo is set to receive a meaty $350 million upfront in cash and stock and is eligible to receive up to $2.37 billion in milestone payments, in addition to royalties. In return, Biogen gets the rights to two Sangamo preclinical compounds: ST-501 (for use in tauopathies including Alzheimer’s disease) and ST-502 (for synucleinopathies including Parkinson’s disease).

“The partnership represents a lower-cost way to expand its work in neurologic disease,” Credit Suisse’s Evan Seigerman said in a note, referring to Biogen.

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Spark los­es an­oth­er top ex­ec in the wake of $4.3B takeover by Roche — re­port

Days after bidding farewell to co-founder Kathy High, Spark Therapeutics — now operating under Roche — has one more opening on its C-suite.

Kathy Reape

Kathy Reape, who joined the Philadelphia-based biotech in 2016 as head of clinical R&D and became chief medical officer in 2018, is reportedly set to leave.

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'The head­lines are the head­lines, but': Bio­Marin talks up po­ten­tial sav­ings as he­mo­phil­ia gene ther­a­py launch looms

BioMarin execs are still staying tight-lipped about their pricing plans for what is poised to be the world’s first hemophilia gene therapy. But as the company enters the final regulatory stretch and approaches a potential launch this summer, they are also dropping more hints to get investors ready.

First thing to know: They really, really don’t expect an advisory committee to be convened for valrox, which is under priority review, to pop up before its PDUFA date on August 21.

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Vlad Coric (Photo Credit: Andrew Venditti)

Bio­haven scores CGRP OK for acute mi­graine — can the com­mer­cial team catch up with Al­ler­gan on its de­but?

Seven years after spinning out of Yale, Biohaven has entered the ranks of commercial-stage biotechs.

The FDA handed down an OK for its CGRP drug, rimegepant, as an acute treatment. Dubbed Nurtec, the orally dissolving pill will join Allergan’s (soon to be AbbVie’s) Ubrelvy and Lilly’s Reyvow on the market amid a new wave of migraine therapies reshaping the disease space.

In a pivotal Phase III trial, Nurtec hit the co-primary endpoints on pain freedom and freedom from most bothersome symptoms at two hours post dose, proving superior to placebo.

Mi­cro­bio­me Q&A: New study maps the vagi­na's 'op­ti­mal mi­cro­bio­ta' — and its im­pli­ca­tions for bio­phar­ma

The widely-held notion that the “optimal” vaginal microbiota is dominated by one strain of lactic-acid producing bacteria has now been challenged in a new paper, published in Nature Communications on Wednesday, which used advanced gene sequencing methods to map out the most comprehensive gene catalog of the human vaginal microbiome.

Things have changed in the more than 50 years since the concept of vaginal microbiota transplants was proposed and subsequently tainted by a Texas-based gynecologist who transplanted the vaginal fluid of women who had bacterial vaginosis into healthy females, suspecting he had isolated the bacteria responsible for the condition.

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