For Rigel, a sur­pris­ing place­bo re­sponse spurs a PhI­II fail, stock beat­ing. But it's been here be­fore

A Cal­i­for­nia biotech fa­mil­iar with speed bumps ran in­to an­oth­er ear­ly Wednes­day as it tries to push its on­ly ap­proved drug in­to an­oth­er in­di­ca­tion.

Rigel Phar­ma­ceu­ti­cals re­port­ed a Phase III fail for its bleed­ing dis­or­der drug fos­ta­ma­tinib, say­ing the pri­ma­ry end­point did not achieve sta­tis­ti­cal sig­nif­i­cance when com­pared to place­bo. The biotech at­tempt­ed to in­duce a durable he­mo­glo­bin re­sponse in pa­tients with warm au­toim­mune he­molyt­ic ane­mia, or wAI­HA, but came up short due to what ex­ecs said were “ge­o­graph­i­cal dif­fer­ences” be­tween the drug and place­bo co­horts.

Wolf­gang Dum­mer

In par­tic­u­lar, Rigel ob­served place­bo arm pa­tients in east­ern Eu­ro­pean coun­tries achieve high­er rates of durable re­sponse than those in the ac­tive co­hort. A post-hoc analy­sis showed a sta­tis­ti­cal­ly sig­nif­i­cant drug re­sponse for Amer­i­can, Cana­di­an, Aus­tralian and west­ern Eu­ro­pean pa­tients, but it’s not yet clear what caused the dis­crep­an­cy, CMO Wolf­gang Dum­mer said on an in­vestor call Wednes­day morn­ing.

What­ev­er the rea­son, in­vestors were not thrilled with the fi­nal out­come. Rigel shares $RIGL were slashed in half in ear­ly Wednes­day trad­ing, falling be­low $1 apiece for the first time.

The biotech is at­tempt­ing to ex­pand fos­ta­ma­tinib’s foot­print in­to oth­er bleed­ing dis­or­ders af­ter it was ap­proved in 2018 to treat adults with chron­ic im­mune throm­bo­cy­tope­nia who failed on pre­vi­ous treat­ments. Brand­ed as Tavalisse, the drug was be­ing stud­ied in 90 wAI­HA pa­tients across the globe.

Over­all, re­searchers ran­dom­ized the pa­tients 1-to-1 to the drug and place­bo groups. Of the 45 in­di­vid­u­als tak­ing fos­ta­ma­tinib, 16 saw durable he­mo­glo­bin re­spons­es, com­pared to 12 of 45 in the place­bo group. Those re­spec­tive rates, 35.6% and 26.7%, trans­lat­ed to a p-val­ue of p=0.398.

But Rigel ex­ecs in­sist­ed the place­bo re­sponse from east­ern Eu­ro­pean pa­tients spurred on the Phase III miss. Ac­cord­ing to Rigel’s analy­sis, nine of the 12 place­bo re­spon­ders came from this part of the world.

Asked on Wednes­day’s call whether the com­pa­ny found such a place­bo re­sponse sur­pris­ing, Dum­mer an­swered in the af­fir­ma­tive and blamed the rel­a­tive lack of oth­er avail­able ther­a­pies.

“In east­ern Eu­rope, drugs like rit­ux­imab are less reg­u­lar­ly avail­able, so the pa­tients that are out there are ap­par­ent­ly less treat­ment-ex­pe­ri­enced, and the sites found the pa­tients that were more re­cent­ly di­ag­nosed with AI­HA,” Dum­mer said. “Now is that a sur­prise? I don’t know how any­body would be able to pre­dict what pre­cise pa­tients would en­roll in the study, oth­er than say­ing bi­o­log­ics are less avail­able in east­ern Eu­ro­pean coun­tries.”

Dum­mer added in re­sponse to a fol­low-up ques­tion that the Russ­ian in­va­sion of Ukraine did not af­fect the study’s re­sults, say­ing “not one” place­bo re­spon­der came from ei­ther coun­try. Most of the place­bo re­spon­ders came from Bul­gar­ia and the Czech Re­pub­lic, Dum­mer said.

Raul Ro­driguez

De­spite the miss in this study, CEO Raul Ro­driguez said Rigel is hope­ful it can come to an agree­ment with the FDA on the best path for­ward for ap­proval. The meet­ing will like­ly take place ei­ther in the third or fourth quar­ter this year, he said.

Rigel is no stranger to head­winds, par­tic­u­lar­ly with fos­ta­ma­tinib, as the drug’s ear­li­er road to ap­proval was lit­tered with set­backs. In 2016, a Phase III study for im­mune throm­bo­cy­tope­nia missed the pri­ma­ry af­ter a pa­tient in the place­bo group achieved a re­sponse in ad­di­tion to those tak­ing the drug.

While Rigel’s first Phase III came in sta­tis­ti­cal­ly sig­nif­i­cant with a p-val­ue of p=0.03, the oth­er’s sin­gle place­bo re­sponse in­duced a p=0.26 p-val­ue. But the FDA went ahead with the throm­bo­cy­tope­nia ap­proval, with reg­u­la­tors will­ing to over­look the miss and make the drug avail­able to pa­tients with­out an ad­vi­so­ry com­mit­tee.

With Wednes­day’s tri­al harken­ing back to the 2018 sit­u­a­tion, Ro­driguez pro­ject­ed con­fi­dence that this next FDA go-around would be no dif­fer­ent.

“Those pa­tients got a prod­uct that was im­mense­ly help­ful and we be­lieve these [wAI­HA] pa­tients de­serve no less,” Ro­driguez said.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

Endpoints Premium

Premium subscription required

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

Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

Dutch biotech starts liq­ui­da­tion af­ter end­ing PhI­II in GVHD

A 13-year-old Dutch biotech is going through a liquidation process after an unexpected end to its Phase III trial testing whether its combination of two monoclonal antibodies was superior to Incyte’s Jakafi.

Xenikos had hoped to prove its investigational therapy, named T-Guard, was better than Jakafi at garnering a complete response in patients experiencing life-threatening complications in which new cells from a hematopoietic stem cell transplant begin to fight the body. Jakafi was approved for the indication, steroid-refractory acute graft-versus-host disease, in May 2019.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.

Eliot Forster, F-star CEO (Rachel Kiki for Endpoints News)

F-star gets down to the wire with $161M sale to Chi­nese buy­er as na­tion­al se­cu­ri­ty con­cerns linger

With the clock ticking on F-star Therapeutics’ takeover by a Chinese buyer, the companies are still scrambling to remove a hold on the deal from the US government’s Committee on Foreign Investment in the United States.

F-star and invoX Pharma said they are “actively negotiating” with CFIUS “about the terms of a mitigation agreement to address CFIUS’s concerns regarding potential national security risks posed by the transaction.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 157,500+ biopharma pros reading Endpoints daily — and it's free.