Armed with a new chief fol­low­ing the un­ex­pect­ed pass­ing of long­time CEO Thomas Neff last year, Fi­bro­Gen is off to the races with its con­tro­ver­sial As­traZeneca-part­nered ane­mia drug. The FDA has ac­cept­ed the com­pa­ny’s ap­pli­ca­tion to mar­ket the oral ther­a­py — which is po­si­tioned to re­place the stan­dard of care — in pa­tients with chron­ic kid­ney dis­ease re­gard­less of dial­y­sis sta­tus.

The drug, rox­adu­s­tat, which is de­signed to stim­u­late the pro­duc­tion of red blood cells by mim­ic­k­ing the ef­fect of high al­ti­tude in hu­mans was ap­proved in Chi­na last year — mark­ing per­haps the first in­stance of a multi­na­tion­al phar­ma­ceu­ti­cal com­pa­ny As­traZeneca paving the way for the sale of a med­i­cine in Chi­na, be­fore the Unit­ed States or Eu­rope.

Fi­bro­Gen and As­traZeneca are locked in a race with Ake­bia, whose ex­per­i­men­tal drug vadadu­s­tat has a sim­i­lar mech­a­nism of ac­tion. But piv­otal vadadu­s­tat da­ta are not ex­pect­ed un­til lat­er in 2020. The dom­i­nant drugs for ane­mia in the Unit­ed States are red-blood-cell boost­ing ery­thro­poiesis-stim­u­lat­ing agents (ESA) from Am­gen. The stan­dard-of-care does, how­ev­er, come with high car­dio risks — but giv­en the steep over­all mor­tal­i­ty rate for this pa­tient pop­u­la­tion, it is a risk reg­u­la­tors con­sid­er ac­cept­able.

Healthy kid­neys pro­duce a hor­mone called ery­thro­poi­etin (EPO), which prompts the bone mar­row to make red blood cells that car­ry oxy­gen through­out the body. If dis­eased or dam­aged, kid­neys are un­able to make enough EPO, re­sult­ing in few­er blood cells, and even­tu­al­ly ane­mia.

Fi­bro­Gen, which orig­i­nal­ly de­vel­oped the drug, has part­nered with As­traZeneca since 2013. On Tues­day, the com­pa­ny — which brought on Lil­ly vet En­rique Con­ter­no to take over the reins last month — said the FDA was ex­pect­ed to make its de­ci­sion by De­cem­ber 20 — trig­ger­ing a $50 mil­lion mile­stone pay­ment from As­traZeneca.

“(R)eas­sur­ing­ly, the FDA si­mul­ta­ne­ous­ly ac­cept­ed the NDA fil­ing for both DD (dial­y­sis-de­pen­dent) and NDD (non-dial­y­sis de­pen­dent) in­di­ca­tions, which should par­tial­ly re­move some of the neg­a­tive over­hang on FGEN’s stock as­so­ci­at­ed with lin­ger­ing skep­ti­cism sur­round­ing the prospects for a suc­cess­ful fil­ing and ap­proval in the more con­tro­ver­sial NDD in­di­ca­tion,” SVB Leerink’s Ge­of­frey Porges wrote in a note.

“Al­though a pri­or­i­ty re­view now ap­pears to be off the ta­ble, the PDU­FA date time­line re­mains con­sis­tent with our ex­pec­ta­tions for an Ad­Com to oc­cur some­time in Q3 2020.”

While rox­adu­s­tat did meet the main goal of en­hanc­ing he­mo­glo­bin lev­els in a pair of piv­otal stud­ies, the drug has a check­ered past.

Last spring, Fi­bro­Gen came un­der fire for mask­ing some un­sa­vory safe­ty da­ta in­di­cat­ing the drug could un­der­whelm in key mar­ket seg­ments — in the top-line mes­sag­ing of ‘pos­i­tive’ pooled safe­ty da­ta on the drug from two sets of re­sults on ma­jor car­dio events (MACE and MACE+) re­quired by US and Eu­ro­pean reg­u­la­tors. The mes­sag­ing in­spired a short at­tack bet­ting that rox­adu­s­tat would come up short when re­searchers un­veil the hard num­bers on the piv­otal safe­ty da­ta on ma­jor car­dio events com­pared to place­bo and EPO.

Then, in No­vem­ber, some con­cerns were as­suaged when As­traZeneca broke out the pooled haz­ard ra­tios on rox­adu­s­tat safe­ty. In­ves­ti­ga­tors as­sessed the drug against place­bo for non-dial­y­sis de­pen­dent CKD pa­tients, and against EPO in dial­y­sis pa­tients, in­clud­ing a pop­u­la­tion of pa­tients new-to-dial­y­sis, or in­ci­dent dial­y­sis. But even at its worst haz­ard ra­tio on the MACE end­point, re­searchers showed rox­adu­s­tat’s safe­ty pro­file was com­pa­ra­ble to EPO — which damp­ened the block­buster ex­pec­ta­tions that would have come with achiev­ing su­pe­ri­or­i­ty.

Mean­while, some crit­ics panned the analy­sis be­cause the com­pa­nies looked at the full in­tent-to-treat pop­u­la­tion. As place­bo pa­tients were switched to EPO, they were more like­ly to ex­pe­ri­ence CV events, swing­ing the pen­du­lum in rox­adu­s­tat’s fa­vor.

“Ma­jor de­bates re­volve around whether it’s go­ing to ac­tu­al­ly be ap­proved and if it’s a broad la­bel in DD and NDD and if they get a black box (we as­sume yes be­cause FDA is su­per con­ser­v­a­tive – and we think Street un­der­stands that’s prob­a­ble so we like the up­side if they do not get a black box),” Jef­feries’ an­a­lyst Michael Yee wrote in a note.

“We think FDA is on board with the sta­tis­tics and da­ta (per FGEN’s FDA meet­ing min­utes, dis­cus­sions, and di­a­log), and part­ners AZN and Astel­las have been pos­i­tive (vo­cal­ly) on the re­sults. AZN wouldn’t have helped file and paid a large $50M mile­stone if they didn’t be­lieve in the drug.”

Ri­val Ake­bia’s da­ta is now in fo­cus.

Yee said he ex­pect­ed the com­pa­ny’s drug, vadadu­s­tat, to hit the end­points of on ef­fi­ca­cy and “non-in­fe­ri­or­i­ty” on CVOT safe­ty ver­sus EPO, like Fi­bro­Gen $FGEN. “But we will look to see if they can hit on “su­pe­ri­or­i­ty” to EPO on in­ci­dent dial­y­sis since this is where FGEN had “su­pe­ri­or” MACE CV da­ta of +30% ben­e­fit in a pooled analy­sis.”

So­cial im­age: Fi­bro­gen

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

US regulators cleared an ultra-rare drug from Pharming Group, by way of Novartis, on Friday afternoon.

The Dutch biotech said the FDA greenlit leniolisib for an immunodeficiency disease known as activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome, or APDS. People 12 years and older can receive the oral drug, to be marketed as Joenja, beginning early next month, Pharming said, five days ahead of the decision deadline set by the FDA as part of a priority review.