UPDATED: After patient fatality, Hanmi loses Boehringer, gains Roche in $800M-plus cancer-partner shuffle

It was a case of win one, lose one this week for South Korea's Hanmi Pharmaceutical. It picked up a lucrative licensing deal with Roche ($RHHBY), only to be swiftly hit by news that another big-name partner--Boehringer Ingelheim--was handing back rights to a lung cancer drug after severe side effects cropped up in a trial.

Investors took a dim view of the latest development, and Hanmi shares were on the slide Friday, falling around 18% as the news of Boehringer's decision sank in. According to an Endpoints report, Boehringer took the decision after “a comprehensive re-evaluation of all available clinical data and recent advances in the treatment of EGFR mutation-positive lung cancer.” The drug has however been linked to several cases of severe toxicity which left one patient dead. 

The $773 million deal with Boehringer for third-generation EGFR inhibitor olmutinib (HM61713) was seen as an endorsement of Hanmi's R&D expertise when it was signed last year. It also appeared to signal that the Korean firm was on course in its bid to push beyond generics and into branded pharmaceuticals.

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The seriousness of the side effects--said to include two cases of toxic epidermal necrolysis (one of which caused the fatality) and one case of Stevens-Johnson syndrome--dealt a fatal blow to the project as far as Boehringer is concerned. Hanmi can, however, keep the $65 million it received so far in upfront and milestone payments. 

HM61713 had been billed as a possible competitor to AstraZeneca's ($AZN) third-generation EGFR inhibitor Tagrisso, which is used when other drugs in the class--Roche/Astellas' market-leading Tarceva, AZ's Iressa and Boehringer's second-generation drug Giotrif--stop working. 

Despite the setback, Hanmi will draw comfort from a new deal with Roche's Genentech unit that, in terms of top-line value, more than compensates for the loss of the Boehringer contract. 

Genentech has stumped up $80 million upfront for worldwide rights to HM95573, a pan-RAF inhibitor currently in Phase I testing, with another $830 million in milestone payments on offer. 

The drug is designed to target the mitogen-activated protein kinase (MAPK) signaling pathway, which was one of the first pathways discovered to be important for cancer. It plays a pivotal role in how cells grow and divide, critical features for cancer progression.

The deal is a welcome endorsement of Hanmi's work, as it comes from a company with a 25-year history of research into MAPK signaling. Roche has already brought two drugs to market that target the pathway, MEK inhibitor Cotellic and BRAF inhibitor Zelboraf. 

Hanmi's drug slots in alongside these two products as it blocks other proteins in the pathway--RAS and KRAS--that, like MEK and BRAF, are involved in the activation of genes that spur cell division.

Genentech's director of oncology business development, Kinney Horn, told FiercePharma that the company intends to evaluate HM95573 in multiple tumors that harbor RAS or BRAF mutations, both alone and in combination with other drugs.

"RAS is mutated in approximately 30% of all cancers and KRAS is mutated in approximately 22% of cancers, including in pancreatic, colorectal and NSCLC tumors," said Kinney. "This makes it a potential target and major unmet need in oncology."

Hanmi will carry out initial clinical trials of HM95573, while Genentech will provide clinical development and biomarker support. The drug is expected to start a Phase Ib clinical trial next year. 

In addition to Boehringer and Roche, Hanmi has also signed a €400 million licensing deal with Sanofi ($SNY) for diabetes drugs and a $690 million partnership with Eli Lilly ($LLY) for the development of autoimmune treatments, as well as a wide-ranging R&D collaboration with Johnson & Johnson ($JNJ).

Related Articles:
Hanmi's $200M China plant likely to make branded drugs versus generics
Boehringer bets up to $730M on a new lung cancer drug
Sanofi inks a $4.2B diabetes deal, playing pipeline catch-up with Novo and Lilly
Janssen the latest Big Pharma to join Hanmi's South Korea deal machine
South Korea's Hanmi eyes branded drugs, fast-paced R&D and China push to grow

Editor's note: This story was updated with information about the side effects and patient death that arose in the Boehringer-Hanmi trial.

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