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.

Regeneron CEO Leonard Schleifer speaks at a meeting with President Donald Trump, members of the Coronavirus Task Force, and pharmaceutical executives in the Cabinet Room of the White House (AP Photo/Andrew Harnik)

OWS shifts spot­light to drugs to fight Covid-19, hand­ing Re­gen­eron $450M to be­gin large scale man­u­fac­tur­ing in the US

The US government is on a spending spree. And after committing billions to vaccines defense operations are now doling out more of the big bucks through Operation Warp Speed to back a rapid flip of a drug into the market to stop Covid-19 from ravaging patients — possibly inside of 2 months.

The beneficiary this morning is Regeneron, the big biotech engaged in a frenzied race to develop an antibody cocktail called REGN-COV2 that just started a late-stage program to prove its worth in fighting the virus. BARDA and the Department of Defense are awarding Regeneron a $450 million contract to cover bulk delivery of the cocktail starting as early as late summer, with money added for fill/finish and storage activities.

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Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Covid-19 roundup: Squab­bles with gov­ern­ment de­lay Mod­er­na’s PhI­II — re­ports; No­vavax se­cures largest Warp Speed deal yet: $1.6B

A much-anticipated Phase III trial for Moderna’s Covid-19 vaccine is being held up as the company delayed submitting trial protocols and sparred with government scientists on how to run the study and even what the benchmark for success should be, Reuters reported.

Moderna, the first US company to put their vaccine into human testing, was supposed to enter a 30,000-person study this month in partnership with the NIH to determine whether it can prevent infection. STAT reported last week that the trial was facing delays over the protocol, but that a July start was still possible. Neither the NIH nor Moderna ever disclosed a specific date the trial should start, but Reuters reported that the agency had hoped to begin on July 10.

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In­vestors give ail­ing Unum a lease on life and a whole new suite of ex­per­i­men­tal can­cer drugs

Investors, it seems, are willing to give Unum Therapeutics one last shot — or at least one last shot to a company of that name.

The ailing cancer biotech, beset by a series of clinical holds and multiple failed lead programs, announced today that they’ve acquired Kiq LLC and that investors are putting in $104 million to advance Kiq’s pipeline of kinase inhibitors. Unum shareholders will now own only 16.2% of the company and CEO Chuck Wilson indicated that the cell therapies the biotech has worked on since its founding may be on their way out, saying Unum will “explore strategic options” for those products.

RA Cap­i­tal dou­bles down on Sid­dhartha Mukher­jee's vi­sion for a new cell en­gi­neer­ing ap­proach, lead­ing Vor's $110M Se­ries B

Vor Biopharma is muscling up.

CEO Robert Ang, who was reluctant to divulge the headcount when discussing his move from Neon Therapeutics to Vor last August, readily offered that the team has grown from 6 to 50 in less than a year. The biotech is moving to a larger office on Cambridge Parkway Drive in weeks, giving it more space to complete the IND-enabling work and manufacturing scale-up — conducted by a CDMO partner — in preparation for clinical trials planned for the first half of 2021.

Cel­lec­tis slammed af­ter pa­tient dies and FDA slaps a hold on their tri­al for an off-the-shelf CAR-T for mul­ti­ple myelo­ma

Cellectis was slammed after the market close on Monday as the biotech reported that the FDA demanded it hit the brakes on their MELANI-01 trial for their off-the-shelf cell therapy UCARTCS1A after one of the patients in the study died of treatment-related cardiac arrest.

The multiple myeloma patient had previously been treated unsuccessfully with various therapies, noted the biotech, and had been given dose level two (DL2) of their allogeneic CAR-T.

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Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Following a successful Phase III study in April showcasing the safety and potential of its new sleep drug, Idorsia posted some mixed news in the second Phase III study, but that won’t stop a planned filing aimed at regulatory approval.

The drug, a dual orexin receptor antagonist (DORA) called daridorexant, was found to significantly improve sleep maintenance and subjective total sleep time in 25 mg doses, replicating results from the first Phase III study. However, improvements in sleep onset and daytime functioning narrowly missed statistical significance, despite numerical consistency with the April study.

UP­DAT­ED: Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA finally granted an accelerated OK for Immunomedics’ Trodelvy, we already got a very strong hint that their confirmatory Phase III study in metastatic triple-negative breast cancer was a success.

That’s because the independent data safety monitoring committee recommended that the trial be stopped early. But just what pointed them to the conclusion was still unclear.

“We do not know the totality of their decision other than it’s pretty evident that the primary endpoint was met; otherwise they could not request to halt the study,” Behzad Aghazadeh, the executive chairman, told Endpoints News at the time.

Shoshanna Shendelman, Applied Therapeutics CEO (Applied Therapeutics)

A lit­tle biotech slaps back at a 'crim­i­nal' short at­tack, vow­ing to pur­sue a pros­e­cu­tion of their case

As short attacks go, Biotech Research Partners’ assault on Applied Therapeutics’ “cherry picked” data and a variety of so-called red flags didn’t cause a whole lot of damage. Ahead of the July 4 holiday, its shares $APLT were dinged and showed signs of quick recovery.

But that didn’t stop an incendiary response, as the biotech swung into action bright and early Monday morning.

Applied Therapeutics accused the authors of the short report of manipulating graphs and figures, misrepresenting data and included factual misrepresentations — all of which added up, in their view, to fraud.

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