Karyopharm shares tank af­ter FDA in­sid­ers slam their case on the ef­fi­ca­cy of a can­cer drug with “sig­nif­i­cant tox­i­c­i­ty”

Karyopharm’s at­tempt to gain an ac­cel­er­at­ed ap­proved for se­linex­or as a treat­ment for drug-re­sis­tant cas­es of mul­ti­ple myelo­ma is in se­ri­ous jeop­ardy. And in­vestors know it.

Their stock $KP­TI plum­met­ed 46% as an­a­lysts ab­sorbed a high­ly crit­i­cal as­sess­ment of their drug — an oral XPO1 in­hibitor — ahead of next Tues­day’s ex­pert pan­el re­view.

Giv­en the his­to­ry of the FDA with these kinds of re­views, Tues­day’s as­sess­ment will like­ly be harsh.

Bat­ting back the op­ti­mistic as­sess­ment the biotech gave se­linex­or, the in­ter­nal FDA re­view con­cludes that there’s pre­cious lit­tle ev­i­dence that the drug has any sig­nif­i­cant val­ue on its own. Just as bad, the drug has been tied to high rates of tox­i­c­i­ty and a high­er death rate when it was test­ed in a ran­dom­ized con­trolled study for acute myeloid leukemia.

“Treat­ment with se­linex­or is as­so­ci­at­ed with sig­nif­i­cant tox­i­c­i­ty,” the re­view states un­am­bigu­ous­ly. The sin­gle arm study that is be­ing used to seek ac­cel­er­at­ed ap­proval demon­strat­ed a 60% rate of se­ri­ous ad­verse events. Al­most 9 out of 10 pa­tients re­quired a dose mod­i­fi­ca­tion due to serous drug re­ac­tions. And a quar­ter of the pa­tients bowed out of the study.

The com­bi­na­tion drug that was used in their pro­posed piv­otal — dex­am­etha­sone — has a his­tor­i­cal re­sponse rate of 10-27% at high dos­es, says the FDA. They could see no re­sponse for the drug when used as a monother­a­py, and even as a com­bo they could see on­ly “lim­it­ed ef­fi­ca­cy.” 

As for the claimed over­all re­sponse rate of 25%, most of those were on­ly par­tial re­spons­es.

An­oth­er chal­lenge: There are 9 drugs ap­proved for treat­ing mul­ti­ple myelo­ma — 4 in the last 4 years. The im­plic­it ques­tion there is, why should the agency ap­prove this drug as num­ber 10?

Giv­en the lim­it­ed ef­fi­ca­cy and sig­nif­i­cant tox­i­c­i­ty demon­strat­ed in this pop­u­la­tion, it is un­clear whether treat­ment with se­linex­or-dex­am­etha­sone pro­vides a clin­i­cal­ly mean­ing­ful ben­e­fit that out­weighs the risks of treat­ment. The lim­i­ta­tions of in­ter­pret­ing safe­ty and ef­fi­ca­cy from a sin­gle arm tri­al, and lack of sin­gle agent ac­tiv­i­ty of se­linex­or cou­pled with his­tor­i­cal da­ta show­ing ac­tiv­i­ty of dex­am­etha­sone in RRMM, add to the chal­lenges in in­ter­pret­ing the re­sults of the piv­otal study in sup­port of the pro­posed in­di­ca­tion.

That’s not good.

An­oth­er black eye was earned for the com­pa­ny’s at­tempt to sup­ply some re­al world ev­i­dence to back up their pitch — which the FDA es­sen­tial­ly re­ject­ed. And an­a­lysts didn’t over­look the vot­ing ques­tion: Should the agency wait for the piv­otal Phase III da­ta from the BOSTON study be­fore the drug hits the mar­ket?

It doesn’t take a ge­nius to fill in the blank on that one.

Jonathan Chang at SVB Leerink notes:

While we were ful­ly ex­pect­ing the tox­i­c­i­ties of se­linex­or to be a key dis­cus­sion point, we view ques­tion­ing the in­ter­pretabil­i­ty of se­linex­or’s ef­fi­ca­cy da­ta as a neg­a­tive sur­prise. Our MEDA­Corp KOL checks have in­di­cat­ed that ef­fi­ca­cy da­ta from the STORM study sug­gest that se­linex­or is an ac­tive drug. No­tably, some of the ef­fi­ca­cy da­ta cit­ed by the FDA for dex alone are gen­er­at­ed in an ear­li­er-line pa­tient pop­u­la­tion (our da­ta ta­bles at­tached). The draft vot­ing ques­tion for the pan­el is “Should ap­proval of se­linex­or be de­layed un­til re­sults of the ran­dom­ized phase 3 tri­al, BOSTON, are avail­able?”. Re­call the Phase III BOSTON study is eval­u­at­ing se­linex­or + Vel­cade + dex (SVd) vs. Vel­cade + dex (Vd) in re­lapsed/re­frac­to­ry mul­ti­ple myelo­ma with da­ta ex­pect­ed by YE19. Ul­ti­mate­ly, po­ten­tial de­lay of ap­proval un­til the BOSTON re­sults are avail­able would be a neg­a­tive up­date vs. our as­sump­tions.

Janet Woodcock (Greg Nash/Pool via AP Images)

'I re­al­ly don’t look back': Janet Wood­cock on her tran­si­tion away from drugs

Janet Woodcock may have one of the most historically long and drug-intense tenures in FDA history, but her new role is outside of all things pharma and the once-acting FDA commissioner isn’t looking back.

“No I really don’t look back,” Woodcock told Endpoints News via email on Monday morning. “Yes I will be transitioning. Longer discussion on infrastructure needed.”

Co­pay coupons gone wrong, again: Pfiz­er pays al­most $300K to set­tle com­plaints in four states

Pfizer has agreed to pay $290,000 to settle allegations of questionable copay coupon practices in Arizona, Colorado, Kansas, and Vermont from 2014 to 2018.

While the company has not admitted any wrongdoing as part of the settlement, Pfizer has agreed to issue restitution checks to about 5,000 consumers.

A Pfizer spokesperson said the company has “enhanced its co-pay coupons to alleviate the concerns raised by states and agreed to a $30,000 payment to each.”

Delaware court rules against Gilead and Astel­las in years-long patent case

A judge in Delaware has ruled against Astellas Pharma and Gilead in a long-running patent case over Pfizer-onwed Hospira’s generic version of Lexiscan.

The case kicked off in 2018, after Hospira submitted an Abbreviated New Drug Application (ANDA) for approval to market a generic version of Gilead’s Lexiscan. The drug is used in myocardial perfusion imaging (MPI), a type of nuclear stress test.

Taye Diggs (courtesy Idorsia)

Idor­sia inks an­oth­er celebri­ty en­dors­er deal with ac­tor and dad Taye Dig­gs as Qu­viviq in­som­nia am­bas­sador

Idorsia’s latest Quviviq insomnia campaign details the relatable dad story of a well-known celebrity — actor and Broadway star Taye Diggs.

Diggs stopped sleeping well after the birth of his son, now more than 10 years ago. Switching mom-and-dad nightly shifts to take care of a baby interrupted his sleep patterns and led to insomnia.

“When you’re lucky enough to be living out your dream and doing what you want, but because of something as simple as a lack of sleep, you’re unable to do that, it felt absolutely — it was treacherous,” he says in an interview-style video on the Quviviq website.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.

Belén Garijo, Merck KGaA CEO (Kevin Wolf/AP Images for EMD Serono)

Mer­ck KGaA pumps €440M in­to ex­pand­ing and con­struct­ing Irish man­u­fac­tur­ing fa­cil­i­ties

The area of Ireland famous for Blarney Castle and its cliffsides along the Atlantic Ocean is seeing Merck KGaA expand its commitment there.

The German drug manufacturer is expanding its membrane and filtration manufacturing capabilities in Ireland. The company will invest approximately €440 million ($470 million) to increase membrane manufacturing capacity in Carrigtwohill, Ireland, and build a new manufacturing facility at Blarney Business Park, in County Cork, Ireland.

Rep. Katie Porter (D-CA) (Michael Brochstein/Sipa USA/Sipa via AP Images)

House Dems to Sen­ate lead­er­ship: Quick­ly move a rec­on­cil­i­a­tion bill with drug price ne­go­ti­a­tion re­forms

Twenty House Democrats, including Reps. Katie Porter of California and Susan Wild of Pennsylvania, are calling on Senate leaders to move quickly with a reconciliation bill (meaning they only need a simple majority for passage) with prescription drug pricing reforms, and to include adding new authority for Medicare to negotiate drug prices.

They also called on the Senate to specifically follow suit with the House passage of a $35 per month insulin cap (as Senate Majority Leader Chuck Schumer’s deadline for a vote on that provision has come and gone), and to cap Medicare Part D costs at $2,000 per year for seniors.

An NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

'Xeno­trans­plan­ta­tion is com­ing': New NE­JM pa­per gives de­tailed look in­to 2 pig-to-hu­man kid­ney trans­plant cas­es

The thymokidney is a curious organ, if you could call it that. It’s a sort of Frankensteinian creation — a system of pig thymus embedded underneath the outer layer of a pig’s kidney, made for human transplantation.

In the first case of pig-to-human xenotransplantation of a kidney into a brain-dead patient, the thymokidney quietly featured front and center.

In that experiment, which took place in September of last year, NYU researchers led by Robert Montgomery sutured a pig thymokidney onto the leg of a brain-dead 66-year-old woman. That case was widely reported on by a horde of major media outlets, including the New York Times, the BBC, and an in-depth feature by USA Today.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.

Phillip Gomez, SIGA CEO

UP­DAT­ED: On the back of SIGA Tech­nolo­gies' win with the FDA, the mon­key­pox virus sees the com­pa­ny spring­ing to fur­ther ac­tion

As the cases of monkeypox now sit at well over 100 worldwide and have spread to multiple continents, the orders for any type of vaccine against monkeypox are seeing nations and medical bodies looking to get their hands on anything and everything. And now SIGA Technologies seems to be getting in on the action.

According to Euronews, SIGA Technologies, a pharmaceutical company that is focused on providing medical countermeasures to biological and chemical attacks, is now in talks with several European authorities looking to stockpile its antiviral that can counter monkeypox. The drug known as tecovirimat or Tpoxx was approved by the FDA in 2018 as a vaccine for smallpox but was approved by the European Medicines Agency to also act against monkeypox, cowpox and complications from immunization with vaccinia.

Vlad Coric, Biohaven CEO

UP­DAT­ED: Fresh off $11.6B sale to Pfiz­er, New Bio­haven hits Phase III set­back just weeks af­ter Vlad Coric chalked up promise

When Pfizer bought up Biohaven’s migraine portfolio in the largest M&A deal of the year earlier this month, Biohaven CEO Vlad Coric promised the rest of the pipeline, which will live on under the umbrella of New Biohaven, still has a lot to offer. But that vision took a dent Monday as the drugmaker revealed it’s once again flopped on troriluzole.

The glutamate regulator failed to meet the primary endpoint on a Phase III study in patients with spinocerebellar ataxia, an inherited disorder that impairs a person’s ability to walk, speak and swallow. SCA can also lead to premature death.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.