Eas­ing con­cerns, Fi­bro­Gen, As­traZeneca se­cure FDA date for their ane­mia drug in broad chron­ic kid­ney dis­ease pop­u­la­tion

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

CDC’s Robert Redford, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

'Ex­treme­ly po­lit­i­cal' — Trump neuters FDA's at­tempt to strength­en vac­cine EUA, ques­tions need to length­en process

Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

CEO Markus Warmuth (Monte Rosa)

Monte Rosa rakes in $96M Se­ries B as it pre­pares 'mol­e­c­u­lar glue' plat­form for IND-en­abling stud­ies

About four months after completing an extension to its Series A, Monte Rosa Therapeutics is putting its next foot forward with another heap of cash.

The Boston-based biotech is back with $96 million in Series B financing with a goal to get its lead program ready for IND-enabling studies by the end of the year. Though Monte Rosa is keeping its specific target a secret for now, the company has been researching how to utilize its protein degradation technology in breast cancer and non-small cell lung cancer, among other areas.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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Chair of FDA's vac­cine ad­comm — who's al­so a lead in­ves­ti­ga­tor of Mod­er­na's vac­cine — re­cus­es her­self from Covid-19 talks

When the FDA’s Vaccines and Related Biological Products Advisory Committee meets next month to discuss the development and authorization of Covid-19 vaccines, the chairwoman won’t be there.

Hana El Sahly has recused herself from the expert panel’s review of the topic, citing her role as a lead investigator in Moderna’s Phase III trial, Reuters reported. An associate professor of virology and microbiology at Baylor College of Medicine in Houston, El Sahly was appointed the chairwoman last year.

Jim Roberts and Brian Finrow (Lumen Bioscience)

With a $4M fed­er­al grant, Lu­men jumps in­to the Covid-19 treat­ment race

It’s been less than a month since Lumen Bioscience announced a $16 million Series B to engineer spirulina — a nutrient-packed super food — for diseases like traveler’s diarrhea, norovirus and C. difficile colitis. And now, the biotech has pulled in another $4 million to do the same for Covid-19.

The approach is quite similar to other gastrointestinal targets the company is pursuing, co-founders and Brian Finrow and Jim Roberts said. The Seattle-based company is working on a camelid antibody cocktail to combat GI infection common among Covid-19 patients. In a study published in the American Journal of Gastroenterology, a majority of Covid-19 patients showed GI and respiratory symptoms, and 25% had only GI symptoms.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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