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.

Microcap biotech Seelos Therapeutics is halting enrollment of its study in spinocerebellar ataxia type 3 (also known as Machado-Joseph disease) because of “financial considerations,” and in order to focus on other studies, the company said today, adding that the pause would be temporary.

The study will continue with the patients who have already enrolled, and the data from them will be used to decide whether to continue enrolling others in the future.

DC District Court Judge Christopher Cooper today granted Vanda Pharma’s request to require the FDA to disclose more info on the complete response letter for its sleep disorder drug Hetlioz.

The melatonin receptor agonist is approved by the FDA to treat non-24-hour sleep-wake disorder, a circadian rhythm disorder. But in 2018 Vanda filed a supplemental application to market Hetlioz as a treatment for jet lag, which the FDA rejected in August 2019, with few details on what Vanda needed to correct course, according to the company.