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.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,900+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,900+ biopharma pros reading Endpoints daily — and it's free.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,900+ biopharma pros reading Endpoints daily — and it's free.

We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.

Ver­sant-backed Chi­nook gets a $65M launch round for its dis­cov­ery quest in a resur­gent kid­ney field

Versant is once again stepping off the beaten track in biotech to see if they can blaze a trail of their own in a field that has looked too thorny to many investors for years.

The venture group and their partners at Apple Tree are bringing their latest creation out of stealth mode today. Born in Versant’s Inception Sciences’ Chinook Therapeutics is betting that its preclinical take on kidney disease can get an early lead among the companies starting up in the field.

Sir An­drew Dil­lon, NICE's first — and on­ly — chief ex­ec­u­tive to step down next year

Using a laptop borrowed from his former employer, South London’s St George’s Hospital, Sir Andrew Dillon set about establishing NICE — launched by the then health secretary Frank Dobson — in 1999.  On Thursday, the UK cost-effectiveness watchdog said its first and only chief executive — Dillon — is stepping down in March 2020.

Back in the day, decisions about which drugs and interventions were funded by the National Health Service (NHS) were made at the local level, but this ‘postcode prescribing’ system was fraught with skewed healthcare deployment making the structure unsustainable. A national system was deemed necessary — and NICE was formed to bridge that gap.