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.

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’ 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.

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.

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.