Still reel­ing from re­jec­tion, Bio­Marin re­ports a glimpse of those 2-year val­rox da­ta FDA was look­ing for — but is it enough to change reg­u­la­tors' minds?

Bio­Marin now has the Phase III da­ta it needs to re­file val­rox, its gene ther­a­py for he­mo­phil­ia A, at the EMA — and pos­si­bly con­vince the FDA to re­con­sid­er its re­quire­ment.

Pulling from a to­tal of 134 pa­tients who had been fol­lowed up for a mean of 71.6 weeks, the biotech ze­roed in on a sub­group that was rolled over from a non-in­ter­ven­tion­al study. Among those 112 pa­tients, the an­nu­al­ized bleed­ing rate was re­duced by 84% com­pared to pro­phy­lac­tic Fac­tor VI­II re­place­ment. The one-time in­jec­tion of val­rox al­so cut mean an­nu­al­ized Fac­tor VI­II in­fu­sion by 99% (p <0.0001).

While an in­ves­ti­ga­tor hailed it as “the first sta­tis­ti­cal ev­i­dence demon­strat­ing ABR su­pe­ri­or­i­ty in a gene ther­a­py tri­al,” an­a­lysts not­ed the re­sults are rough­ly in line with in­vestor ex­pec­ta­tions.

For them, a dif­fer­ent num­ber from an­oth­er, small­er sub­group might mat­ter more for the drug’s fu­ture: Fac­tor VI­II lev­els af­ter two years.

Two-year safe­ty and ef­fi­ca­cy fol­low-up, af­ter all, was the da­ta that FDA reg­u­la­tors were look­ing for as they slapped a re­jec­tion on Bio­Marin’s first BLA. So far, 17 pa­tients who had been di­rect­ly en­rolled in­to the Phase III GEN­Er8-1 tri­al with­out go­ing through the ob­ser­va­tion pe­ri­od had reached that mark.

On av­er­age, Fac­tor VI­II ac­tiv­i­ty was 42.2 IU/dL at one-year and de­clined to 24.4 IU/dL at 2 years. The me­di­an lev­els were low­er (14.7 IUdL at Year 2), re­flect­ing wide sta­tis­ti­cal dis­tri­b­u­tion.

The com­pa­ny not­ed that the ex­pres­sion re­mained in the range that pro­vides ef­fi­ca­cy, with a mean an­nu­al­ized bleed­ing rate of 0.9 (and me­di­an 0.0) episodes per year. Bio­Marin said it will sub­mit the da­ta to the EMA, whose re­quest for a full year’s worth of da­ta spurred it to with­draw its ini­tial ap­pli­ca­tion, in the sec­ond quar­ter of 2021 as planned while ask­ing the FDA to “re­view two-year da­ta re­quest.”

But an­a­lysts are skep­ti­cal.

“(W)hile the pace of F8 de­cline here looks mod­er­ate­ly bet­ter than the ph1/2, the dropoff in ex­pres­sion from year 1 to 2 is still mean­ing­ful, and we still be­lieve that clin­i­cal dura­bil­i­ty (the ques­tion of how long will it last) will re­main top of mind for clin­i­cians, es­pe­cial­ly giv­en that there are oth­er good treat­ment op­tions for He­mo­phil­ia A,” Stifel’s Paul Mat­teis wrote, adding that the FDA had giv­en writ­ten feed­back rec­om­mend­ing two-year da­ta from all pa­tients. “Thus, while you nev­er know, it’s hard for us to see why specif­i­cal­ly these da­ta would move the agency from their con­ser­v­a­tive stance.”

Be­sides, Joseph Schwartz of SVB Leerink not­ed, the prod­uct pro­file and re­spon­der rates re­main un­clear. More da­ta might be need­ed, for in­stance, to clar­i­fy what role steroids might play in the reg­i­men as the cur­rent re­sults sug­gest their proac­tive ad­min­is­tra­tion does not seem to im­prove Fac­tor VI­II ac­tiv­i­ty.

“Al­though the da­ta are top-line, there are many stand­ing ques­tions such as how steroids will be im­ple­ment­ed in the re­al world, as­sum­ing ap­proval, and how much ex­pres­sion vari­abil­i­ty is there/are there enough ad­e­quate re­spon­ders to Roc­ta­vian,” he wrote.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

It’s official: Janet Woodcock is now the acting chief of the FDA.

And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed.

To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come.

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What’s next for End­points — and how to sup­port our in­de­pen­dent bio­phar­ma news mis­sion

The firehose of biopharma news is gushing these days.

That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style.

Eli Lil­ly's an­ti­body cuts risk of Covid-19 by up to 80% among the most vul­ner­a­ble — but will it have a place next to vac­cines?

Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus.

But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear.

Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance.

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Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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Northway Biotech's new manufacturing facility in Greater Boston

North­way Biotech sets up shop in Boston hub, look­ing to court more cus­tomers with bi­o­log­ics-fo­cused plant

Getting a foot in the door in Boston’s bustling biopharma hub is a rite of passage for many companies, but it comes with a steep price tag. Lithuanian CDMO Northway — now with a new moniker — will set up a new plant in close proximity, and it’s hoping its biologics focus will find a willing customer base.

Northway Biotech (formerly Northway Biotechpharma) on Wednesday held a virtual grand opening ceremony for its $40 million Waltham, MA facility — a 30,000 square-foot cGMP manufacturing and process development plant that will widely expand on the company’s previous capabilities.

News brief­ing: Five pub­lic biotechs, over 2 days, raise $883M from fresh of­fer­ings; Bel­gian biotech ex­pands Se­ries B fund­ing

The wave of biotech IPOs we’ve been seeing in the last few days underscores that the public markets remain one of the key channels for fresh investments in drug R&D. And that trend was in full view this week as a slate of biotechs nailed down hundreds of millions of dollars in fresh funds.

One of the big winners of the week is Editas $EDIT, which nailed $231 million to back its pioneering work on a gene editing platform. The biotech sold 3.5 million shares at $66 each.

With patent con­cerns loom­ing, Roche gets a new pri­or­i­ty re­view on block­buster IPF drug

Seven years after the FDA first approved Esbriet, the blockbuster Roche IPF drug is getting an expedited review for a second indication.

On Thursday, the agency gave Esbriet priority review for unclassified interstitial lung diseases, or forms of pulmonary inflammation and scarring that don’t fit easily into the over 200 known types of ILD. The move comes 10 months after Esbriet received breakthrough designation and sets Roche up for a decision by May.

Michelle McMurry-Heath, BIO CEO (BIO via YouTube)

BIO looks to re­struc­ture, lay­ing off staff amid chal­lenge to the trade org's nor­mal face-to-face style

The biopharma industry, on the whole, had a red-letter year in 2020 amid Covid-19, with fundraising at an all-time high and major players speeding vaccines ahead to approval. But for BIO, the industry’s leading trade organization, the pandemic has prompted a reconsideration of the game plan.

BIO will pivot to digital as the Covid-19 pandemic continues to rage, making “some staff reductions” as it looks to bring its roughly 37,000 in-person meetings each year to the web, the organization said Thursday.

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