Daiichi suspends enrollment in rare tumor trial after two patients develop liver side effects

Daiichi Sankyo

Daiichi Sankyo's ambition to build a pipeline of new oncology drugs may have just taken another big hit. The Japanese drugmaker has been forced to stop recruiting patients into a late-stage trial of pexidartinib after "serious liver toxicity" was seen in two patients.

The trial involved patients with tenosynovial giant cell tumor (TGCT), a rare, nonmalignant tumor also known as pigmented villonodular synovitis that affects the joint or tendon sheath and currently has no FDA-approved drug treatment. 

No new patients will be enrolled into the ENLIVEN study, but the subjects recruited to date will continue on therapy--given as capsules twice a day--with careful monitoring of their liver function.  

If the liver toxicity emerges as a serious problem, it could raise a question mark over pexidartinib's chances of getting approval for TGCT, which according to analysts at Credit Suisse could be a $350 million market for the drug. 

The overall impact on Daiichi Sankyo could be much greater, however. The first-in-class colony stimulating factor-1 receptor (CSF1R) inhibitor is also in clinical trials for a host of cancer applications, including bigger indications such as glioblastoma, malignant melanoma, prostate cancer and breast cancer. It is also being investigated in combination with Merck & Co.'s anti-PD-1 immunotherapy Keytruda (pembrolizumab) for advanced melanoma and other solid tumors.

"Upon completion of the study with currently enrolled patients, Daiichi Sankyo will conduct and report a thorough evaluation of the results and consider any and all appropriate next steps," said Dr. Antoine Yver, EVP and global head of oncology R&D, in a statement

Daiichi Sankyo has made no secret of its ambition to build an industry-leading cancer portfolio, setting aside a $4.4 billion war chest earlier this year to buy up new candidates. The company needs new drugs to plug the hole due to arrive next year when it loses patent protection for big-selling high blood pressure drug Benicar (olmesartan medoxomil and hydrochlorothiazide) in fiscal 2017.

The latest knockback also comes shortly after it suffered another pipeline disappointment. HER3 inhibitor patritumab failed to show efficacy in a Phase III trial in non-small cell lung cancer (NSCLC) patients reported in June, but remains in development for head and neck cancer in combination with Eli Lilly's EGFR inhibitor Erbitux (cetuximab) and platinum-based chemotherapy.

Originally developed by Daiichi Sankyo's Plexxikon subsidiary, pexidartinib is currently leading the field among CSF1R inhibitors but has some pretty big competitors on its heels. Five Prime Therapeutics and partner Bristol-Myers Squibb have their candidate cabiralizumab in Phase II trials for TGCT, while Roche has emactuzumab in midstage testing for ovarian, fallopian tube and peritoneal cancer and Amgen has AMG 820 in Phase I/II cancer trials.

Roche's drug was in trials for TGCT but was discontinued in that indication earlier this year. Thus far, the company hasn't given a reason for that decision. 

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