Fol­low­ing lethal tox re­port, Boehringer scraps plans for high-speed de­vel­op­ment, kills $730M Han­mi deal

Boehringer-In­gel­heim de­cid­ed to abrupt­ly wash its hands of a $730 mil­lion can­cer drug col­lab­o­ra­tion with Han­mi af­ter a South Ko­re­an min­istry linked the ther­a­py to sev­er­al cas­es of se­vere tox­i­c­i­ty — one of which left a pa­tient dead. Boehringer con­firmed the re­port in a re­ply to End­points News ear­ly Fri­day af­ter­noon, say­ing Ko­re­an of­fi­cials had tracked three cas­es of tox­ic epi­der­mal necrol­y­sis, which can spur he­m­or­rhag­ing and res­pi­ra­to­ry fail­ure.

Ko­re­an of­fi­cials ap­proved ol­mu­tinib (HM61713)  — an oral, EGFR mu­ta­tion-spe­cif­ic TKI — in May af­ter a rapid Phase I/II pro­gram. And Boehringer used the Ko­re­an ap­proval to tout its own plans to hus­tle along an FDA and EMA ap­pli­ca­tion lat­er this year af­ter com­plet­ing a Phase II tri­al. The FDA fol­lowed up with a break­through drug des­ig­na­tion de­signed to speed de­vel­op­ment ef­forts.

“The South Ko­re­an Au­thor­i­ty is­sued a drug safe­ty let­ter to­day, avail­able here (in Ko­re­an),” a Boehringer spokesper­son said in an email. “The let­ter refers to two cas­es of tox­ic epi­der­mal necrol­y­sis, one of them fa­tal, and one case of Stevens-John­son-Syn­drome (non-fa­tal). Pa­tient safe­ty is our high­est pri­or­i­ty. We pre­vi­ous­ly in­formed reg­u­la­to­ry au­thor­i­ties, in­clud­ing the FDA, about rel­e­vant safe­ty da­ta re­lat­ed to ol­mu­tinib, in­clud­ing side ef­fects such as se­vere skin re­ac­tions. For stud­ies for which Boehringer In­gel­heim is re­spon­si­ble all in­ves­ti­ga­tors re­ceived time­ly com­mu­ni­ca­tions re­gard­ing these find­ings and were in­struct­ed to in­form their pa­tients ac­cord­ing­ly. A com­pre­hen­sive re-eval­u­a­tion of all avail­able clin­i­cal da­ta and re­cent ad­vances in the treat­ment of EGFR mu­ta­tion-pos­i­tive lung can­cer con­tributed to the de­ci­sion to re­turn the com­mer­cial rights of ol­mu­tinib to Han­mi.”

In a fol­lowup, 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.

Boehringer en­rolled treat­ment-re­sis­tant EGFR T790M mu­ta­tion-pos­i­tive lung can­cer pa­tients in its study. But it didn’t men­tion any of the safe­ty is­sues in its state­ment to­day, say­ing on­ly that it de­cid­ed to ex­it the deal af­ter a “re-eval­u­a­tion of all avail­able clin­i­cal da­ta on ol­mu­tinib and re­cent treat­ment ad­vances made in the treat­ment of EGFR mu­ta­tion-pos­i­tive lung can­cer.”

Han­mi said it was keep­ing the $65 mil­lion in cash it had re­ceived so far.

Quot­ing the health min­istry, The Ko­rea Her­ald re­port­ed that two pa­tients died (Boehringer says that the sto­ry is in­cor­rect) af­ter ex­pe­ri­enc­ing se­ri­ous ad­verse skin events in the Boehringer study. Then they cit­ed a lo­cal on­col­o­gy pro­fes­sor who said that the tri­als were ter­mi­nat­ed af­ter in­ves­ti­ga­tors tried re­duc­ing the dosage, but found that the ef­fi­ca­cy had di­min­ished sub­stan­tial­ly. While some of the de­tails of their sto­ry are be­ing dis­put­ed by a Boehringer rep­re­sen­ta­tive, who in­sist­ed re­peat­ed­ly on hav­ing them re­moved from this ar­ti­cle, the Her­ald al­so post­ed their piece on the safe­ty prob­lems well be­fore the com­pa­ny is­sued a state­ment to us clar­i­fy­ing what had hap­pened with the drug, of­fer­ing in­for­ma­tion that was clear­ly miss­ing from Boehringer’s orig­i­nal re­lease.

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.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.

Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.

UP­DAT­ED: Gilead keeps push­ing trove of Trodelvy da­ta as it seeks to be­come new stan­dard of care in TNBC

Gilead is continuing to churn out results for its newly approved drug Trodelvy, and #ESMO21 is the latest stop on the data train.

The biopharma put out new quality of life data in second-line patients with metastatic triple-negative breast cancer, saying that a sub-analysis from their Phase III study showed significant and clinically meaningful improvements in health-related quality of life over standard of care.