FDA ex­perts turn thumbs down on Karyopharm’s trou­bled pitch for an ac­cel­er­at­ed OK — but not all of them

The Karyopharm team $KP­TI took on a tough chal­lenge on Tues­day, try­ing to over­come an over­whelm­ing­ly crit­i­cal re­view by FDA reg­u­la­tors in win­ning over a pan­el of out­side ex­perts brought in to re­view their pitch for an ac­cel­er­at­ed ap­proval of se­linex­or for mul­ti­ple myelo­ma.

They lost, but nev­er­the­less found con­sid­er­able sup­port for this drug among the pan­elists.

The pan­el vot­ed 8 to 5 against an ap­proval, say­ing af­fir­ma­tive­ly that the FDA should take a wait-and-see at­ti­tude un­til the ran­dom­ized piv­otal study wraps to­ward the end of the year.

Karyopharm’s stock — bat­tered last Fri­day — took an­oth­er tum­ble af­ter the bell, drop­ping 19%.

FDA rep­re­sen­ta­tives were po­lite about it, but out­lined mul­ti­ple prob­lems with the da­ta that Karyopharm pre­sent­ed: Miss­ing da­ta due to dropouts, un­ac­cept­able re­al world ev­i­dence, an ab­sence of ev­i­dence of pos­i­tive sin­gle agent ac­tiv­i­ty (there are neg­a­tive re­sults), most­ly par­tial re­spons­es and much, much more — all in­for­ma­tion that the biotech failed to spot­light in the lead-up to the NDA. In one study the FDA cit­ed, the over­all sur­vival rate was worse in the se­linex­or arm.

Then there was the tox­i­c­i­ty pro­file, with a high fre­quen­cy of treat­ment emer­gent ad­verse events among pa­tients tak­ing the drug. The agency cit­ed a 94% rate of grade 3 or grade 4 ad­verse event. 10 deaths were due to a fa­tal ad­verse event in the main sin­gle arm study used for the ac­cel­er­at­ed ap­proval. And 9 in 10 pa­tients re­quired a dose mod­i­fi­ca­tion, with a ma­jor­i­ty re­quir­ing 2 mod­i­fi­ca­tions.

Giv­en the lim­it­ed ef­fi­ca­cy and tox­i­c­i­ty, the FDA as­sert­ed, “it is un­clear whether the ben­e­fit out­weighs the risk.” 

That’s not some­thing you want to hear in a pan­el re­view.

Mean­while, a piv­otal tri­al is un­der­way, and if a pa­tient de­mand­ed it, there are av­enues that pa­tients could use to get the drug with­out an ac­cel­er­at­ed ap­proval.

The FDA’s on­col­o­gy pan­el is not a tough group, on av­er­age, to win over. There’s a big ap­petite for new drugs to treat can­cer pa­tients who have failed mul­ti­ple ther­a­pies, and a low bar on safe­ty. Not get­ting past that at this stage will like­ly set the bar high­er for when Karyopharm comes back with their piv­otal da­ta — pro­vid­ed that the agency goes ahead and re­jects it, as they have clear­ly in­di­cat­ed that they plan to.

The sig­nif­i­cant num­ber of votes in Karyopharm’s fa­vor, de­spite the FDA’s po­si­tion, does un­der­score just how anx­ious many of these ex­perts are about of­fer­ing ear­ly ap­provals, even when mul­ti­ple drugs are ap­proved for the same in­di­ca­tion. The bias is in fa­vor of more op­tions, which was clear­ly on dis­play here.

Dana Far­ber’s David Har­ring­ton joined the mi­nor­i­ty in fa­vor of pro­vid­ing an ac­cel­er­at­ed ap­proval. “The da­ta are not con­clu­sive in ei­ther di­rec­tion,” he said, but…”I think we do pa­tients some po­ten­tial ben­e­fit if this is used con­struc­tive­ly.”

Just a slight nudge in its fa­vor from reg­u­la­tors may well have been enough to win an ap­proval, de­spite the tri­al is­sues. And that once again gets back to whether the de­vel­op­ers have a close work­ing re­la­tion­ship with the agency.

The biotech’s case wasn’t good enough, though, with the ma­jor­i­ty sid­ing with the reg­u­la­tors who have the fi­nal say now. Tox­i­c­i­ty was a ma­jor is­sue with the ex­perts who sided against a quick OK.

At best, Karyopharm like­ly faces a lengthy de­lay re­fil­ing an NDA. And that is if the Phase III da­ta are pos­i­tive.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Pfiz­er, Sarep­ta and two oth­ers sug­gest Duchenne drug safe­ty is­sues tied to "class ef­fect"

Since the first experimental Duchenne gene therapy programs came about, the space has proven rife with safety issues and patient deaths in clinical trials. Pfizer and three biotechs now think they’ve found a reason why.

The four companies suggested there may be a “class effect” causing the adverse events in Duchenne gene therapies, they wrote in a new study. They specifically highlighted how side effects in five patients across three trials, who all showed muscle weakness with cardiac involvement, were “strikingly similar.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,400+ biopharma pros reading Endpoints daily — and it's free.

Pre­sent­ing a live End­points News event: Man­ag­ing a biotech in tur­bu­lent times

Biotech is one of the smartest, best educated industries on the planet. PhDs abound. We’ve had a long enough track record to see a new generation of savvy, experienced execs coming together to run startups.

And in these times, they are being tested as never before.

Biotech is going through quite a rough patch right now. For 2 years, practically anyone with a decent resume and some half-baked ideas on biotech could start a company and get it funded. The pandemic made it easy in many ways to pull off an IPO, with traditional road shows shut down in exchange for a series of quick Zoom meetings. Generalist investors flocked as the numbers raised soared into the stratosphere.

De­spite fed­er­al ef­forts to di­ver­si­fy clin­i­cal tri­als, progress re­mains 'stag­nan­t' — re­port

While calls to diversify clinical trials have grown louder in recent years — gaining support from federal agencies such as the FDA and NIH — progress has largely stalled, according to a new report from the National Academies of Sciences, Engineering and Medicine.

Swaths of patients in racial and ethnic minority groups, as well as LGBTQIA+, pregnant and older adult populations continue to be left out of clinical trials. While some advances have been made in the last 30 years — women now account for roughly half of clinical trial participants — growth in other areas remains stagnant, according to the report, which was mandated by Congress and sponsored by the NIH.

Paul Chaplin, Bavarian Nordic president and CEO

Bavar­i­an Nordic se­cures BAR­DA con­tract for small­pox vac­cine

It seems that smallpox vaccination production is weighing on the mind of the US government. And manufacturer Bavarian Nordic is the latest company to benefit.

Just a few days after Emergent, a company that has made government contracts its lifeblood, acquired the exclusive rights to Tembexa from Chimerix, with a $225 million cash payment and an expected BARDA contract, the agency has offered a contract for smallpox vaccine production.

Lina Khan, FTC chair (Saul Loeb/Pool via AP)

New FTC com­mis­sion­er could turn the tide for an in­ves­ti­ga­tion in­to PBMs

The Senate last week voted along party lines, 51-50, with Vice President Kamala Harris casting the tie-breaker, to make President Biden appointee Alvaro Bedoya the deciding vote on a split 2-2 Federal Trade Commission.

The addition of Bedoya to the FTC could not only spell more trouble for biopharma M&A activity, as he may align with his Democrat partners to break the FTC ties, but it may also mean that FTC Chair Lina Khan has what she needs to move forward on a study around the pharma middlemen known as pharmacy benefit managers.

Patty Murray (D-WA) (Graeme Sloan/Sipa USA)(Sipa via AP Images)

Sen­ate user fee reau­tho­riza­tion bill omits ac­cel­er­at­ed ap­proval re­forms, shows wide gaps with House ver­sion

The Senate health committee on Tuesday released its first version of the bill to reauthorize all the different FDA user fees. But unlike the House version, there are only a few controversial items in the Senate’s version, which does not address either accelerated approval reforms or clinical trial diversity (as the House did).

While it’s still relatively early in the process of finalizing this legislation (the ultimate statutory deadline is the end of September), the House and Senate, at least initially, appear to be starting off in different corners on what should be included.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,400+ biopharma pros reading Endpoints daily — and it's free.

Warren Buffett, Berkshire Hathaway CEO

Berk­shire Hath­away pulls out of Ab­b­Vie, Bris­tol My­ers Squibb in­vest­ments

It looks like Warren Buffett is sticking to ice cream and railroads for the moment.

The billionaire CEO of Berkshire Hathaway backed out of two major holdings in the pharma industry, Forexlive first reported, including a $410 million investment in AbbVie and a $324.4 million stake in Bristol Myers Squibb.

The move comes after Berkshire abandoned its Teva shares just last quarter, Bloomberg reported.

Long-ex­pect­ed UK lay­offs im­mi­nent for No­var­tis fol­low­ing sale

Nearly a year ago, more than 200 workers at Novartis’ Grimsby, UK, facility were able to hang on to their jobs after the pharma closed a Switzerland site as a part of its workforce restructuring plan. Now, it looks like those employees’ time is up, as the site has been sold, Grimsby Telegraph reported today.

The manufacturing site has been sold to Humber Industrials, a subsidiary of International Process Plants. None of the current staff members will be working with the new owners, however.