Lethal ex­per­i­men­tal can­cer drug from Han­mi, Boehringer killed three pa­tients — re­port

Ko­re­an health of­fi­cials have tied the deaths of three pa­tients to a can­cer drug launched by Han­mi Phar­ma­ceu­ti­cals and part­nered with Boehringer In­gel­heim, ac­cord­ing to a fol­lowup sto­ry in The Ko­rea Her­ald.

Cit­ing a re­port from the coun­try’s Min­istry of Food and Drug Safe­ty, which was re­leased by Rep. Kwon Mi-hyuk to­day, the three were a 75-year-old pa­tient who died in late 2015, a 57-year-old who died in March and a 54-year-old who died in June.

Al­to­geth­er eight pa­tients died in the study, ac­cord­ing to the Her­ald’s re­port­ing of the min­istry re­view, with 29 “se­ri­ous ad­verse events and ad­verse drug re­ac­tions,” though health of­fi­cials have not con­firmed a link with the drug in every case.

Late Fri­day, Boehringer is­sued a tardy re­sponse to End­points News.

“Boehringer In­gel­heim in­formed reg­u­la­to­ry au­thor­i­ties, in­clud­ing the FDA, about rel­e­vant safe­ty da­ta re­lat­ed to ol­mu­tinib, in­clud­ing side ef­fects such as se­vere skin re­ac­tions men­tioned in the drug safe­ty let­ter,” the com­pa­ny said in a state­ment. “At the same time Boehringer In­gel­heim in­formed all in­ves­ti­ga­tors. We al­so made sure pa­tients re­ceived time­ly com­mu­ni­ca­tions and up­dat­ed their con­sents re­gard­ing these find­ings. We are not aware of any ad­di­tion­al of­fi­cial re­port or com­mu­ni­ca­tion is­sued by the South Ko­re­an Au­thor­i­ty.”

Boehringer In­gel­heim abrupt­ly washed its hand of the drug just days ago with­out ini­tial­ly rais­ing any is­sues with deaths or ad­verse events. Queried by End­points News, a spokesper­son for the com­pa­ny pro­vid­ed a state­ment say­ing that Ko­re­an of­fi­cials had is­sued a let­ter re­fer­ring to “two cas­es of tox­ic epi­der­mal necrol­y­sis, one of them fa­tal, and one case of Stevens-John­son-Syn­drome (non-fa­tal).”

The ap­pro­pri­ate reg­u­la­tors, the com­pa­ny added, had been in­formed of “rel­e­vant safe­ty da­ta re­lat­ed to ol­mu­tinib, in­clud­ing side ef­fects such as se­vere skin re­ac­tions.” Boehringer not­ed that the two cas­es of tox­ic epi­der­mal necrol­y­sis oc­curred in two stud­ies: HM-EM­SI-101 and HM-EM­SI-202. The 101 study is list­ed on clin­i­cal­tri­als.gov as spon­sored by Han­mi with Boehringer cit­ed as a col­lab­o­ra­tor.

Not long ago, though, Boehringer — which has paid Han­mi $65 mil­lion of a $730 mil­lion deal — had been ea­ger to see if it could quick­ly put the drug through a mid-stage study and then seek a fast ap­proval.

Back in May, two months af­ter the sec­ond pa­tient death re­port­ed by Ko­re­an of­fi­cials, Boehringer put out a re­lease tout­ing the Ko­re­an ap­proval of the drug, stat­ing:

Ol­mu­tinib (BI 1482694 / HM61713) is a nov­el third-gen­er­a­tion, oral, EGFR mu­ta­tion-spe­cif­ic TKI. It is cur­rent­ly in ac­cel­er­at­ed de­vel­op­ment through the am­bi­tious ELUXA clin­i­cal tri­al pro­gramme with the aim to sub­mit da­ta and ev­i­dence to the US FDA and EU EMA in 2016. The piv­otal Phase II tri­al ELUXA 1 (HM-EM­SI-202 (NCT02485652) is on­go­ing, en­rolling EGFR T790M mu­ta­tion-pos­i­tive lung can­cer pa­tients who have be­come re­sis­tant to pre­vi­ous TKI treat­ment.

“This first ap­proval of ol­mu­tinib is an ex­cit­ing mile­stone for the com­pound and we are work­ing dili­gent­ly to make this nov­el treat­ment op­tion glob­al­ly avail­able to pa­tients and physi­cians as quick­ly as pos­si­ble,” said Boehringer on­col­o­gy chief Jörg Barth, in a state­ment.

Han­mi, mean­while, is now un­der in­ves­ti­ga­tion to see if there was any in­sid­er trad­ing of com­pa­ny stock around the re­port on ad­verse events, which came out just hours af­ter the com­pa­ny com­plet­ed a tie-up with Genen­tech. In the mean­time, Ko­re­an of­fi­cials have re­port­ed­ly de­cid­ed to keep the drug on the mar­ket un­der the con­di­tion­al ap­proval that was hand­ed out ear­li­er in the year. Even though there was one re­port­ed pa­tient death at the time, they said, they had no di­rect link to the drug. Pa­tients would have to be in­formed of the risks, they said, be­fore they were giv­en the drug.

Look­ing to make a big move in­to brand­ed drugs, Han­mi has been rack­ing up a se­ries of part­ner­ships with mar­quee drug de­vel­op­ers. Just yes­ter­day Genen­tech signed on to part­ner on an ear­ly-stage can­cer drug. Last fall, Sanofi paid €400 mil­lion up­front to part­ner with Han­mi on a port­fo­lio of di­a­betes drugs. Be­fore that, there was a pact with Eli Lil­ly worth up to $690 mil­lion on an au­toim­mune drug for a va­ri­ety of dis­eases. And J&J has al­so part­nered with Han­mi, which has been beef­ing up its R&D arm in a con­cert­ed ef­fort to build a port­fo­lio of brand­ed ther­a­pies.

From left to right: Lilian Kim, Associate Director Business Development; John Moller, CEO; Yooni Kim, Executive Director, Asia Operations; Michelle Park, Director South Korea Operations.

Novotech CRO sees 26% growth in Asia tri­al ac­tiv­i­ty from biotechs, but still plen­ty of ca­pac­i­ty

As the Asia-Pacific clinical trials sector continues to grow rapidly, Novotech the Asia-Pacific-based CRO is seeing biotech clinical activity up by 26%. But says there is still plenty of capacity in the region that features advanced medical facilities, supportive regulatory environments, and more than 2.3 billion people, largely treatment naïve, living in urban areas.

China, South Korea and Australia have the most studies registered as recruiting or about to recruit according to ClinicalTrials.Gov.

Pfizer, South San Francisco — Jeff Rumans for Endpoints News

UP­DAT­ED: Pfiz­er takes aim at a flag­ship fran­chise at Sanofi and Re­gen­eron — and scores a few di­rect hits

Count Pfizer in as a top player in the blockbuster game of JAK1 inhibitors.

Over the weekend the pharma giant posted some stellar Phase III efficacy data for their heavyweight contender abrocitinib in atopic dermatitis (eczema) that lines up ahead of a booming Dupixent (dupilumab), a blockbuster in the portfolios of Regeneron and Sanofi. And they put some real distance ahead of Eli Lilly’s trailing Olumiant, which made a delayed initial arrival on the market for rheumatoid arthritis after the FDA hobbled it with some additional hurdles on safety concerns.

JADE-MONO-1 scores well for Pfizer, teeing up what will be an intensely followed breakdown of the JADE MONO-2 data, which the pharma giant recently top-lined as “similar” to the first Phase III when tested against a placebo — a control group that has been easily outclassed by all the drugs in this market niche.

As of now, Pfizer looks to be equipped to run into the review stage — advantaged by a breakthrough therapy designation that is intended to speed up the regulatory process.

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A preda­tor's world? Top an­a­lyst sees the 'haves' and the 'haven't­s' di­verge as biotech bub­bles form — and col­lapse

Josh Schimmer

We’ve all seen the deluge of cash that’s been pouring into biotech from every angle: VCs, IPOs and follow-ons have generated billions in capital for new and emerging drug developers with ready access to some powerful new tech. But Evercore ISI’s Josh Schimmer is asking where we’re headed from here.

His answer is neither apocalyptic nor universally blissful, but if he’s right — and this is a discussion we’re hearing much, much more about at a time of growing economic and industry uncertainty — we may well be at a crossroads that could affect valuations, M&A and the entire global industry that has formed over the past 5 years.

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US mulls tar­iffs on Swiss drug ex­ports, weigh­ing on No­var­tis and Roche –  re­port

The leading Swiss newspaper has reported that the US is considering placing tariffs on pharmaceuticals from Switzerland. Roche and Novartis stock each fell 1% after the news broke.

Neue Zürcher Zeitung reported that US Trade Representative Robert Lighthizer told pharmaceutical representatives the Trump administration was considering the move. Tariffs do not appear to be in the immediate offing, but they would potentially affect Swiss giants Novartis and Roche along with other companies that manufacture in Switzerland, including Merck KGaA and US biotech Biogen, which is currently constructing a new facility in the country.

Neil Kumar, Endpoints

Bridge­Bio drops bid to re­claim Ei­dos af­ter di­rec­tors spurn 3 of­fers

A couple of months ago a newly public BridgeBio turned some heads by disclosing that it had made a bid for subsidiary Eidos Therapeutics in hopes of gobbling up the 34% stake that it doesn’t already own. Two offers later, the parties are calling it off.

A special committee of independent directors at the smaller biotech led by RA Capital’s Rajeev Shah and ex-Portola CEO William Lis first rejected the parent company’s initial offer — which would swap 1.3 BridgeBio shares for each Eidos share — on September 12. In the latest announcement, BridgeBio revealed that it eventually raised the offer to 1.5 shares and made $110 million available for all-cash or mixed consideration options, but Eidos still wasn’t interested.

Mark Foley, Revance

HR vi­o­la­tion push­es Re­vance co-founder out, vault­ing for­mer Zel­tiq chief to the helm

Months after Revance amended the terms of its Botox biosimilar collaboration with Mylan, the Newark, California-based drug developer disclosed its co-founder Dan Browne is stepping down, in what appears to be mysterious circumstances.

The company — which is also developing a rival to Allergan’s formidable Botox franchise — on Monday said Browne is departing “due to misjudgment in handling an employee matter,” that has also culminated in his resignation from Revance’s board of directors.

In-house FDA re­view flags a sus­pi­cious im­bal­ance in deaths as Sh­iono­gi hunts an OK for an­tibi­ot­ic

Shionogi has some big questions to answer if they plan to win an FDA panel’s backing for their new antibiotic.

While investigators have provided positive efficacy data for their new product to treat cases of complex urinary tract infections, an FDA review has flagged an imbalance of deaths between the antibiotic and a control arm. And they want the agency’s outside advisers to take a good hard look at that when they meet on Wednesday.

Cell ther­a­py start­up rais­es $16 mil­lion to fund its quest for the Holy Grail in re­gen­er­a­tive med­i­cine

In 2006, Shinya Yamanaka shook stem cell research with his discovery that mature cells can be converted into stem cells, relieving a longstanding political-ethical blockage and throwing open medical research on everything from curbing eye degeneration to organ printing.

But that process still has pitfalls, including in risk and scalability, and some researchers are exploring another way first hinted at years ago: new technology to convert mature cells directly into other mature cells without the complex and time-consuming process of first making them into stem cells.

Eye­ing $86M, Galera leads a pack of three mod­est biotech IPOs push­ing past high pro­file stum­bles

Exactly one year after kicking off a pivotal Phase III study for its lead drug — a companion for cancer patients receiving radiotherapy — Galera is looking to the Nasdaq for some new cash to complete the clinical work and fuel its commercial drive.

CEO Mel Sorensen has penciled in an $86 million ask, which was filed on the same day as liver disease company 89bio and rare disease diagnostics shop Centogene. The trio marks the first batch of IPO filings in the wake of two highly anticipated but ultimately disappointing public debuts by BioNTech and Vir, signaling dwindling biotech fervor on Wall Street. 89bio and Centogene are seeking $70 million and $69 million, respectively.