Liv­er tox cas­es force Dai­ichi Sankyo to cur­tail re­cruit­ment for PhI­II tri­al of a ‘break­through’ drug

Mah­moud Ghazzi

Two cas­es of se­ri­ous liv­er tox­i­c­i­ty forced in­ves­ti­ga­tors to sus­pend en­roll­ment on Dai­ichi Sankyo’s Phase III pro­gram for its “break­through” drug pex­i­dar­tinib (PLX3397). But both cas­es were non-fa­tal, a com­pa­ny spokesper­son tells End­points News, and the tri­al is head­ed to com­ple­tion af­ter the com­pa­ny de­cid­ed to wrap en­roll­ment a few sub­jects short of their goal.

Dai­ichi Sankyo is test­ing the drug on rare cas­es of tenosyn­ovial gi­ant cell tu­mor (TGCT) among pa­tients who couldn’t qual­i­fy for sur­gi­cal re­moval of the tu­mor. By the time the liv­er tox is­sues ap­peared, the com­pa­ny had al­ready en­rolled 121 of the planned 126 pa­tients and the da­ta mon­i­tor­ing com­mit­tee sug­gest­ed cut­ting en­roll­ment short and tak­ing mea­sures so they could pre­serve the study as a dou­ble-blind­ed test.

“As a re­sult,” Dai­ichi said in a state­ment to End­points, “EN­LIV­EN will con­tin­ue to com­ple­tion in or­der to eval­u­ate its ef­fi­ca­cy and safe­ty end­points. These mea­sures were re­viewed and agreed on by the U.S. Food and Drug Ad­min­is­tra­tion (FDA), and all reg­u­la­to­ry au­thor­i­ties in­volved in the EN­LIV­EN study have been no­ti­fied. All pa­tients cur­rent­ly en­rolled in EN­LIV­EN are in the process of be­ing in­formed about this up­dat­ed safe­ty in­for­ma­tion and will un­der­go re-con­sent for con­tin­ued par­tic­i­pa­tion in the study.”

Dai­ichi Sankyo won the FDA’s break­through ther­a­py des­ig­na­tion for the oral CSF-1R in­hibitor based on its Phase I re­sults post­ed last sum­mer. The same tri­al per­suad­ed the Japan­ese phar­ma com­pa­ny to move straight in­to Phase III. That’s an in­creas­ing­ly com­mon clin­i­cal tri­al strat­e­gy.

“Surgery is the pri­ma­ry treat­ment for TGCT, but for pa­tients with a dif­fuse form of the con­di­tion, the tu­mor is more dif­fi­cult to re­move and has a high rate of re­cur­rence, re­sult­ing in mul­ti­ple com­pli­cat­ed surg­eries and even am­pu­ta­tion in some pa­tients,” not­ed Mah­moud Ghazzi, Dai­ichi Sankyo’s for­mer R&D chief, last sum­mer. Ghazzi left the com­pa­ny last month.

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.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources. 

Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

As­traZeneca's di­a­betes drug Farx­i­ga helps pa­tients with heart dis­ease and with­out di­a­betes in land­mark tri­al

Months ago, data on J&J’s $JNJ Invokana indicated the diabetes drug conferred cardiovascular (CV) benefit in patients who do and do not have preexisting CV disease. On Tuesday, AstraZeneca’s $AZN rival treatment, Farxiga, was shown to cut the risk of CV death or the worsening of heart failure in patients with heart disease, in a landmark trial.

The treatments, in addition to Jardiance from Eli Lilly $LLY, belong to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination.

Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.

Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
Endpoints News

Basic subscription required

Unlock this story instantly and join 57,700+ biopharma pros reading Endpoints daily — and it's free.