Aslan turns fo­cus to bil­iary tract can­cer as lead drug flops in PhII gas­tric can­cer study

About a year af­ter se­cur­ing the full rights to de­vel­op and com­mer­cial­ize var­l­i­tinib from Ar­ray Bio­Phar­ma $AR­RY, Aslan Phar­ma $AL­SN said the drug failed to con­fer a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in tu­mors of pa­tients with gas­tric can­cer in a mid-stage study.

Carl Firth

The Sin­ga­pore-based com­pa­ny — which is run by for­mer BD chief for As­traZeneca Carl Firth and went pub­lic in an un­der­whelm­ing IPO last May — has es­sen­tial­ly aban­doned test­ing the ex­per­i­men­tal drug in pa­tients with gas­tric can­cer and will con­cen­trate on stud­ies in bil­iary tract can­cer and oth­er in­di­ca­tions, it said on Mon­day.

Orig­i­nal­ly de­vel­oped by Ar­ray, the drug is al­so known as ASLAN001 and is an oral, small mol­e­cule that in­hibits the ac­tiv­i­ty of epi­der­mal growth fac­tor re­cep­tors HER1, HER2 and HER4 — which are mu­tat­ed or over­ex­pressed in many tu­mors and typ­i­cal­ly cause un­con­trolled growth. Its mech­a­nism of ac­tion is sim­i­lar to that of Roche’s can­cer drug Her­ceptin, which tar­gets HER2.

In the study, var­l­i­tinib was be­ing test­ed as a first-line treat­ment in pa­tients with gas­tric can­cer in ad­di­tion to a stan­dard chemother­a­py reg­i­men. Af­ter 12 weeks of treat­ment, pa­tients giv­en the drug + chemother­a­py ex­pe­ri­enced an av­er­age tu­mor shrink­age of 22%, while those on chemother­a­py alone saw their tu­mors shrink by 12.5% — how­ev­er that dif­fer­ence was not deemed sta­tis­ti­cal­ly sig­nif­i­cant. Aslan’s shares were down 24% be­fore the bell.

In terms of safe­ty, 73.1% of pa­tients on the ex­per­i­men­tal drug reg­i­men ex­pe­ri­enced a grade 3 or high­er ad­verse event, ver­sus 88.5% of pa­tients on chemother­a­py alone, Aslan said.

Ac­cord­ing to clin­i­cal­tri­, about 50 pa­tients were en­rolled in the study, which, if pos­i­tive, was de­signed to evolve in­to a Phase III tri­al eval­u­at­ing the drug in hun­dreds of pa­tients.

Oth­er than di­et, to­bac­co use, gen­der (male) and age (60-80), gas­tric or stom­ach can­cer is al­so linked to in­fec­tion with H. py­lori bac­te­ria. Over time it can lead to pre­can­cer­ous changes to the in­ner lin­ing of the stom­ach, ac­cord­ing to the Amer­i­can Can­cer So­ci­ety (ACS), which es­ti­mates the num­ber of new cas­es of stom­ach can­cer have de­creased about 1.5% each year over the last decade in the Unit­ed States, al­though in the late 1930s, stom­ach can­cer was the lead­ing cause of can­cer death in the re­gion. In oth­er parts of the world, stom­ach can­cer is much more com­mon, par­tic­u­lar­ly in less de­vel­oped coun­tries, the ACS added.

Mark McHale

“First-line gas­tric can­cer is a very chal­leng­ing in­di­ca­tion to treat and the ma­jor­i­ty of pa­tients present with ad­vanced dis­ease at ini­tial di­ag­no­sis,” Aslan’s COO Mark McHale said in a state­ment. “To date, no tar­get­ed ther­a­pies have been ap­proved to treat gas­tric can­cer with low HER-fam­i­ly ex­pres­sion. Whilst we are dis­ap­point­ed by the study find­ings, we are en­cour­aged by the pos­i­tive safe­ty da­ta and re­main con­fi­dent that var­l­i­tinib’s po­tent pan-HER in­hi­bi­tion has the po­ten­tial to yield ben­e­fits in bil­iary tract can­cer where HER fam­i­ly ex­pres­sion is known to be high.”

Da­ta from a first-line bil­iary tract can­cer study will be pre­sent­ed at a med­ical con­fer­ence lat­er this week, while top-line da­ta from a piv­otal study in sec­ond-line bil­iary tract can­cer are ex­pect­ed in the sec­ond half of 2019, the com­pa­ny said.

“While the var­l­i­tinib clin­i­cal da­ta gen­er­at­ed to date…have demon­strat­ed some ac­tiv­i­ty, we con­tin­ue to want to see more clin­i­cal and mech­a­nis­tic val­i­da­tion for var­l­i­tinib giv­en that bil­iary tract can­cer has his­tor­i­cal­ly been a dif­fi­cult space for drug de­vel­op­ment and the mech­a­nis­tic ad­van­tages of var­l­i­tinib be­ing a pan-HER in­hibitor re­main un­clear, giv­en the im­pli­ca­tions of tar­get­ing HER4 re­main poor­ly un­der­stood. Over­all, while we’re pos­i­tive on Aslan’s Asia fo­cused de­vel­op­ment strat­e­gy and the ex­pe­ri­ence of the man­age­ment team, we want to see more clin­i­cal and mech­a­nis­tic val­i­da­tion for var­l­i­tinib in a cat­a­lyst-rich 2019,” Leerink an­a­lysts wrote in a note.

In 2017, Aslan re­port­ed that var­l­i­tinib in­duced a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in tu­mor size in pa­tients with breast can­cer in a Phase II tri­al, but the drug did not con­fer any im­prove­ments in pro­gres­sion-free sur­vival or over­all sur­vival.

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — and they're prep­ping a pitch to the FDA

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company says that a new analysis of an old dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

Vas Narasimhan. Getty Images

Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

Take­da tees up $420M deal for celi­ac an­ti­dote, con­tin­u­ing R&D re­fo­cus

Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

A dysfunctional digestive system, Arataeus concluded – an imbalance he attributed to a “heat” deficiency in a system he and other Greeks regarded as functioning similarly to an oven – and coined a term: coeliac disease, after the Greek word for abdomen.

UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

Photo credit: Jacquelyn Martin

Where are the in­ter­change­able biosim­i­lars?

In June 2017, Leah Christl, former biosimilar lead at FDA, told a conference in Chicago that interchangeable biosimilars were likely coming to the US market within two years.

And although no interchangeable biosimilar has been approved by FDA yet, and Christl has since moved on to Amgen, progress on interchangeable biosimilars has been slow in the intervening years.

Most recently, Boehringer Ingelheim announced that it has completed, as of last April, a switching study necessary for launching an interchangeable biosimilar for Humira (adalimumab), although the company did not offer any further details on the timing of its submission to FDA or whether there will be an advisory committee to review the data. Boehringer already has an adalimumab biosimilar approved by FDA, which it will launch in the US on 1 July 2023.

FDA re­buffs lit­tle As­ser­tio Ther­a­peu­tic­s' long-act­ing ACTH for­mu­la­tion, shares sink

Tiny Assertio Therapeutics’ shares plunged pre-market on Tuesday, after the FDA has spurned its man-made version of the hormone ACTH, which was being reviewed as a diagnostic for patients presumed to have adrenocortical insufficiency.

The Lake Forest, Illinois-based drugmaker said its development partner West Therapeutic Development had received a complete response letter from the US regulator, which indicated that that certain “pharmacodynamic parameters were not adequately achieved” for the product.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 62,600+ biopharma pros reading Endpoints daily — and it's free.

That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.