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.

UP­DAT­ED: Have a new drug that promis­es to fight Covid-19? The FDA promis­es fast ac­tion but some de­vel­op­ers aren't hap­py

After providing an emergency approval to use malaria drugs against coronavirus with little actual evidence of their efficacy or safety in that setting, the FDA has already proven that it has set aside the gold standard when it comes to the pandemic. And now regulators have spelled out a new approach to speeding development that promises immediate responses in no uncertain terms — promising a program offering the ultimate high-speed pathway to Covid-19 drug approvals.

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In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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Covid 19 roundup: Trump push­es his new fa­vorite, untest­ed drug; CRISPR out­lines crip­pling im­pact of Covid-19

President Trump has a new favorite Covid-19 drug.

After a conversation with Japanese Prime Minister Shinzo Abe, Politico reports, the president is pressuring the FDA to issue emergency use authorization for favipiravir, a flu drug that showed glimpses of success in China but remains unproven and carries a list of worrying side effects. The push comes after a week-plus in which the White House touted a potentially effective but unproven malaria medication despite the concerns of scientific advisors such as NIAID director Anthony Fauci. And Trump ally Rudy Giuliani has been talking up unproven cell therapy efforts on Twitter.

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ITeos nabs $125M as they prep Keytru­da com­bi­na­tion tri­al — if Covid-19 will let them

For iTeos, it turned out, $75 million could only last so long.

Two years after announcing their eye-catching Series B raise, the Belgian biotech is back with an even larger Series B-2: $125 million.

The now $200 million financing illustrates the vast capital available for those with promising new immuno-oncology compounds, particularly those that might be used in combination with existing therapies. In December, iTeos announced a collaboration with Merck to test its lead compound with Keytruda this year. The proceeds will push forward that trial and help fund the ongoing Phase I/II trials for that compound, EOS-850, and a second one, EOS-448.

Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

Back in the BP era — Before Pandemic — the FDA ripped Novartis for its decision to keep the agency in the dark about manipulated data used in its application for Zolgensma while its marketing application for the gene therapy was under review.

Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

You can add Amgen and GSK to the list of deep-pocket drug R&D players who are tailoring their pipeline work to fit a new age of coronavirus.

Following in the footsteps of a lineup of big players like Eli Lilly — which has suspended patient recruitment for drug studies — Amgen and GSK have opted to take a more tailored approach. Amgen is intent on circling the wagons around key studies that are already fully enrolled, and GSK has the red light on new studies while the pandemic plays out.

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Dai­ichi Sankyo sinks $200M in­to new gene ther­a­py tech from Ul­tragenyx

In a leap to the gene therapy space, Daiichi Sankyo has dropped $200 million to access Ultragenyx’s manufacturing technology, providing the rare disease biotech with plenty of cash and a stock boost amid a general cash crunch.

For $125 million in cash and a $75 million equity investment, Daiichi Sankyo has bought a non-exclusive license to the IP around two platforms with which it plans to develop AAV-based gene therapy products. The Japanese pharma is purchasing the stock $RARE at $60 per share, more than a third above its current price of $44.43.

It is 'kind of a proven tech­nol­o­gy': Hep B vac­cine mak­er joins glob­al hunt for coro­n­avirus vac­cine

Using lab-grown proteins that are engineered to mimic the architecture of viruses to induce an immune response, VBI Vaccines is joining the hunt for a coronavirus vaccine — harnessing technology that has initially been proved safe in early trials as a prophylactic for cytomegalovirus (CMV) infection.

Unlike the raft of the companies in the Covid-19 vaccine race — including Moderna, CureVac and J&J — VBI is taking a pan-coronavirus approach, by developing a vaccine that will encompass Covid-19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS).

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As­traZeneca says its block­buster Farx­i­ga proved to be a game-chang­er in CKD — wrap­ping PhI­II ear­ly

If the FDA can still hold up its end of the bargain, AstraZeneca is already on a short path to scooping up a cutting-edge win with a likely approval for their SGLT2 drug Farxiga in cutting the risk of heart failure. Now the pharma giant says it can point to solid evidence that the drug — initially restricted to diabetes — also works for chronic kidney disease, potentially adding a blockbuster indication for the franchise.

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