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.

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Sen­ate Fi­nance Com­mit­tee lobs more bi­par­ti­san pres­sure on­to PBMs

Congress is honing in on how it wants to overhaul the rules of the road for pharmacy benefit managers, with a Senate Finance Committee hearing Thursday serving as the latest example of the Hill’s readiness to make changes to how pharma middlemen operate.

While pledging to ensure patients and pharmacies “don’t get a raw deal,” Finance Committee Chair Ron Wyden (D-OR) laid out the beginning of what looks like a major bipartisan effort — moves the PBM industry is likely to challenge vigorously.

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Nicklas Westerholm, Egetis Therapeutics CEO

Ac­qui­si­tion talks on­go­ing for Swedish rare dis­ease biotech Egetis, shares up al­most 40%

Shares of the Sweden-based rare disease biotech Egetis Therapeutics skyrocketed on Thursday afternoon as the company said it’s engaged in “ongoing discussion” with external parties regarding a “potential acquisition.”

Egetis confirmed rumors with a statement on Thursday while noting that there is no certainty that a takeover offer will be made.

Nonetheless, the possibility of an acquisition has shot up Egetis’ share price. By the afternoon on Thursday, its stock price was {$EGTX.ST} up over 38%. An Egetis spokesperson told Endpoints News in an email that it has no further comments.

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Lu­pus drug de­vel­op­ment mar­ket heat­ing up, while FDA links with ad­vo­ca­cy group to fur­ther ac­cel­er­ate re­search

The long-underserved systemic lupus erythematosus (SLE) market is suddenly buzzing with treatment possibilities. Less than two years after AstraZeneca’s approval for Saphnelo — the first new SLE drug in a decade and joining just one other approved in GSK’s Benlysta – the pipeline of potential drugs numbers in the dozens.

Although most are very early stage — Spherix Global Insights estimates five in Phase II/III — the pharma R&D enthusiasm is catching on among doctors, patients and advocacy groups. On Wednesday, the Lupus Research Alliance and the FDA formed a novel private-public partnership called Lupus Accelerating Breakthroughs Consortium (Lupus ABC) to help advance lupus clinical trial success.

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Stéphane Bancel, Moderna CEO (AP Photo/Markus Schreiber)

Mod­er­na so­lid­i­fies deal with Kenya to build mR­NA man­u­fac­tur­ing fa­cil­i­ty

The mRNA player Moderna is further cementing its presence on the African continent.

Moderna announced on Thursday that it has finalized an agreement with Kenya’s government to partner up and bring an mRNA manufacturing facility to the east African nation. The new facility aims to manufacture up to 500 million doses of vaccines annually. Moderna also said the new facility will have the ability to spike its production capabilities to respond to public health emergencies on the continent or globally.

Luke Miels, GSK chief commercial officer

GSK picks up Scynex­is' FDA-ap­proved an­ti­fun­gal drug for $90M up­front

GSK is dishing out $90 million cash to add an antifungal drug to its commercial portfolio, in a deal spotlighting the pharma giant’s growing focus on infectious diseases.

The upfront will lock in an exclusive license to Scynexis’ Brexafemme, which was approved in 2021 to treat a yeast infection known as vulvovaginal candidiasis, except in China and certain other countries where Scynexis already out-licensed the drug.

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J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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Deborah Waterhouse, ViiV Healthcare CEO

MPP re­cruits three gener­ic man­u­fac­tur­ers to ex­pand use of Vi­iV's in­jectable PrEP drug

ViiV Healthcare has teamed up with the UN-backed Medicines Patent Pool and three generic manufacturers to expand access to medicine that can prevent HIV.

ViiV and the Medicines Patent Pool jointly announced Thursday that the MPP signed sub-licensing agreements with Aurobindo, Cipla and Viatris to manufacture generics of a long-acting form of cabotegravir for HIV pre-exposure prophylaxis (PrEP). As a result of the agreement, the manufacturers will be able to develop, manufacture and supply generic versions of cabotegravir LA in 90 countries — subject to regulatory approvals.