FDA or­ders Karyopharm to halt en­roll­ment for all se­linex­or tri­als, cit­ing in­com­plete safe­ty warn­ing

Late Fri­day night Karyopharm Ther­a­peu­tics $KPT alert­ed in­vestors that the FDA has slapped a par­tial hold on all stud­ies in­volv­ing its lead can­cer drug se­linex­or, halt­ing en­roll­ment for work on a drug that was re­cent­ly tapped for a 2018 fil­ing with the FDA.

Reg­u­la­tors or­dered the par­tial hold af­ter cit­ing, in writ­ing, in­com­plete in­for­ma­tion in a brochure on the drug which in­clud­ed an in­com­plete list of the ad­verse events as­so­ci­at­ed with the drug. The state­ment does not say when the agency first in­formed the com­pa­ny of the par­tial hold, but Karyopharm says that as of Fri­day the com­pa­ny has sup­plied the in­for­ma­tion re­quest­ed to get the hold lift­ed.

Say­ing you’ve re­spond­ed to the FDA at the same time you’re an­nounc­ing a par­tial hold rais­es some ques­tions on tim­ing. How long did the com­pa­ny know about the hold be­fore the alert late Fri­day?

“Karyopharm Ther­a­peu­tics re­ceived the let­ter no­ti­fy­ing the com­pa­ny of the par­tial clin­i­cal hold with­in the past week,” a com­pa­ny spokesper­son said in re­sponse to a query from me. The spokesper­son did not an­swer my query on how many days ago the no­tice ar­rived or whether reg­u­la­tors had told them ver­bal­ly ear­li­er, which is rou­tine.

The sus­pen­sions were flagged on Twit­ter Fri­day, well ahead of the news, af­ter the biotech’s shares slid 10% ahead of the close.

The New­ton, MA-based biotech added that it be­lieves the halt won’t af­fect the de­vel­op­ment time­lines al­ready of­fered. Karyopharm, led by CEO Michael Kauff­man, lists 8 dif­fer­ent clin­i­cal pro­grams for se­linex­or on its web site.

Bri­an Abra­hams at Jef­feries was hap­py to write it off as “just an ad­min­is­tra­tive blun­der.”

Af­ter speak­ing with man­age­ment, our un­der­stand­ing is that this is due to an AE (ad­verse event) ta­ble that had in­ad­ver­tent­ly been re­moved from the in­ves­ti­ga­tor’s brochure and in­formed con­sent forms used in the tri­als in a re­cent ver­sion. FDA re­quest­ed that the ta­ble be up­dat­ed and re-in­sert­ed, and KP­TI has pro­vid­ed that up­dat­ed in­for­ma­tion. Our un­der­stand­ing is that this is pure­ly an ad­min­is­tra­tive blun­der, and that there have been no new safe­ty is­sues or deaths from the drug. While this is not fa­vor­able for their cred­i­bil­i­ty re­gard­ing tri­al con­duct, we be­lieve the com­pa­ny has tak­en ac­tion to im­prove their process­es such that go­ing for­ward hu­man er­ror should not cause an­oth­er mi­nor set­back in their de­vel­op­ment pro­gram.

Karyopharm tout­ed da­ta from a sin­gle-arm study last fall demon­strat­ing a par­tial re­sponse in rough­ly 1 in 5 pa­tients out of 78 evalu­able pa­tients suf­fer­ing from drug-re­sis­tant mul­ti­ple myelo­ma. And they gained a spike in the stock price by com­par­ing that fa­vor­ably to his­tor­i­cal da­ta. The biotech planned to add an­oth­er 120 pa­tients to that study and take the da­ta to the FDA in search of an ac­cel­er­at­ed ap­proval.

Just a few days ago, though, the biotech al­so con­ced­ed that the drug failed a mid-stage study for acute myeloid leukemia. Se­linex­or works by in­hibit­ing the nu­clear ex­port pro­tein XPO1 (al­so called CRM1), trig­ger­ing cell apop­to­sis.

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Turn­ing the cor­ner on treat­ing the root cause of sick­le cell dis­ease

Early in my career, as a medical resident, I saw first-hand the enormous challenges faced by children and adults with sickle cell disease (SCD), a genetic blood disorder that historically has lacked adequate treatment options. People living with this life-long disease are mainly those with ancestors from sub-Saharan Africa, as well as people of Hispanic, South Asian, Southern European and Middle Eastern descent. These patients suffer from devastating physical symptoms, including progressive, eventually fatal, organ damage and excruciating pain. In addition, they encounter emotional, mental and social burdens – non-physical aspects of living with SCD that also take a serious toll on patients and their caregivers.

Rev­o­lu­tion Med shoots for $100M+ IPO — and di­vulges some se­crets about that Warp Dri­ve buy­out

Biotech investors who like to wager on the race to the front of the KRAS market now have a new team to consider.

Revolution Medicines, which extended its reach on RAS with a deal to acquire Warp Drive Bio about 18 months ago, filed their S-1 in search of $100 million-plus. And they gave up a few secrets in the process.

The main clinical claim to fame that Revolution has centers on the SHP2 inhibitor RMC-4630, partnered with Sanofi back in the summer of 2018 — just after John Reed was named the incoming R&D chief. We already knew that the pharma giant handed over $50 million in cash plus a commitment of hundreds of millions more to align itself with Revolution as it makes a fresh foray into oncology. Now we know that Sanofi is also footing 80% of Revolution’s R&D bill on the program, while setting up a smorgasbord of $235 million in development milestones and $285 million in commercial bonuses.

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Olivier Brandicourt, AP Images

#JPM20 ex­clu­sive: Olivi­er Brandi­court fol­lows the Big Phar­ma CEO path to pri­vate eq­ui­ty, join­ing Black­stone ahead of a mam­moth fund de­but

Nick Galakatos Blackstone

Seven months after Olivier Brandicourt’s surprise “early retirement” from Sanofi, he’s back in the game, this time taking meetings at JP Morgan to discuss his new role at Blackstone, where he’s quietly begun work with Nick Galakatos and the life sciences crew.

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Video Re­play: End­points at #JPM20 — news­mak­ers on deal­mak­ing, pric­ing and man­u­fac­tur­ing

On Monday, we held our fourth annual #JPM event — and the team hit a key milestone that I’d like to share with the entire Endpoints News audience: We live-streamed the conversation and had nearly triple the number of executives watching online than we had in the sold-out crowd of 320.

For a media company on a mission to connect the biopharma world in bigger and better ways, we’re proud of how we were able to extend the reach of our franchise event. Paid subscribers were given access to the stream in real time, and now, two days later, we’re opening it up to everyone in this post.

Endpoints@JPM: (left to right) Steve Pearson, Nick Leschly, Bari Talente, Stephen Ubl, John Carroll

#JPM20: 'The NPV is al­ways wrong.' Take­da preps an­oth­er spin­out — this time on psych

Editor’s Note: Endpoints News is reporting live from #JPM20 after kicking things off with an action-packed event, which you can replay here. What follows is a stream of tidbits we have collected while wandering around Union Square in San Francisco. Check back in throughout the week for updates by John Carroll and Jason Mast.

SAN FRANCISCO — A year ago Takeda CEO Christophe Weber and R&D chief Andy Plump arrived at JP Morgan right on the heels of closing their big Shire buyout. Now they’re back after shaking up the portfolio, boosting R&D spending by about 50% to $4.5 billion and adjusting the pipeline — a task which isn’t quite finished yet.

Nick Leschly at Endpoints News' panel at the 2020 JP Morgan Healthcare Conference. Credit: Jeff Rumans

At #JPM20, two CEOs, two rad­i­cal­ly dif­fer­ent ther­a­pies, and a fight to chase down sick­le cell

SAN FRANCISCO – Few CEOs tell a story better than bluebird’s Nick Leschly.

He cuts a Jeff Bezos figure on stage at the Colonial Room, the JP Morgan presentation hall for A-list biotechs: lean and bald, fast-talking and vest-wearing. He explains in simple language, apologizing when he has to brush on the data. It helps that he has a good story to tell.

“We treated them one time,” Leschly tells a packed crowd, gesturing to the slide behind him. “Look what happened.”

The slide shows 9 horizontal bars studded with diamonds. Each bar, he explained, represented a sickle cell patient, and each diamond represented a severe medical event, such as a pain crisis. The diamonds stud one side – before the therapy – and vanish on the other, afterward.

“A 99% reduction in these events — this is a functional cure for sickle cell disease,” Leschly says. “This is unprecedented data.”

Upstairs and an hour later, Ted Love stands before a narrow conference room in his suit and polka-dot tie. Love, the CEO of Global Blood Therapeutics, is a 60-year-old physician. His voice trails off at the end of sentences, and the story he tells is less compelling. There are no cured patients.

“This is the first drug that addresses the root cause of sickle cell disease,” Love says, speaking in front of a slide showing a white pill bottle for GBT’s new drug Oxbryta. “Right in the label, it says that this drug inhibits polymerization.”

In the 60 years after scientists discovered the cause of sickle cell, almost no treatments emerged, even as the condition debilitated hundreds of thousands of Americans, most of them black or Hispanic. But the last few years have seen a resurgence of interest as new technologies have made the disease seem newly beatable.

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Neon Ther­a­peu­tics makes one last re­treat, sell­ing it­self cheap in a bar­gain base­ment M&A deal

Crushed by weak data for what had been their lead drug, Neon Therapeutics is being bought for parts this morning.

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Mark Pruzanski

#JPM20: Af­ter a year of NASH col­laps­es, all eyes on two biotechs

SAN FRANCISCO – It’s not quite Dewey defeats Truman, but Goldman Sachs calling 2019 “The Year of NASH” may well go down in the annals of worst biotech predictions.

Goldman Sachs slapped the label on weeks before 2019’s JP Morgan conference, projecting that long-discussed treatments for the obesity-driven condition suspected to lurk in millions of Americans would begin to bear fruit and investors would move accordingly. That did not quite happen.

“If you look at 2019, it was just a string of disappointing news,” Pascal Prigent, CEO of NASH-focused biotech Genfit, told Endpoints News in an interview.

The Year of NASH, or nonalcoholic steatohepatitis, became a year of NASH failures. Gilead failed two large Phase III trials. CymaBay went from a $1 billion company to a $100 million company after they found their drug was killing patients’ liver cells. Cirius withdrew an $86 million IPO bid after a disastrous readout. Industry-wide, there were few acqusitions in a market often projected to be worth $35 billion.

Gilead, after dominating the NASH discussion at the 2019 JPM, gave one quick mention to the program in their 2020 presentation before pivoting to other drugs.

“As promising as some of the mechanisms looked in earlier stages, when push comes to shove in large study settings, they just haven’t proven out,” Mark Pruzanski, CEO of the NASH-focused biotech Intercept, told Endpoints in an interview.

As biotech turns from 2019, the failures have refocused eyes away from Gilead and back toward two startups, both facing key events in the coming months: Intercept, which first alerted investors to NASH at JPM 2014, and the France-based Genfit.

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