Buoyed by he­mo­phil­ia A gene ther­a­py up­date, Bio­Marin switch­es to head-to-head study -- but shares slide on dura­bil­i­ty con­cerns

With its he­mo­phil­ia A gene ther­a­py poised to go through a piv­otal pro­gram by the end of next year, Bio­Marin $BM­RN set out to boost hopes for its suc­cess with a new batch of Phase I/II da­ta for its val­rox pro­gram (val­oc­toco­gene rox­a­parvovec/BMN 270). But the biotech’s shares turned wob­bly and start­ed to slide on con­cerns that the new num­bers may have re­vealed some longterm weak­ness on ef­fi­ca­cy.

Hank Fuchs

Re­searchers at a con­fer­ence in Glas­gow are point­ing to one of the dosage arms where they tracked a 97% cut in an­nu­al­ized bleed­ing rate. And the biotech now plans to boost the num­ber of pa­tients in a reg­is­tra­tion study so they can pro­vide clear ev­i­dence of the gene ther­a­py’s abil­i­ty to beat the cur­rent stan­dard of care us­ing fac­tor re­place­ment ther­a­py.

The com­pa­ny will in­crease en­roll­ment by 90, tak­ing 130 pa­tients in­to the piv­otal pro­gram af­ter see­ing ev­i­dence of a durable abil­i­ty over 2 years to slash bleed rates in pa­tients..

“In or­der to make this op­tion avail­able with the ur­gency and da­ta sup­port that peo­ple with se­vere he­mo­phil­ia A de­serve, we plan to raise the sam­ple size of our reg­is­tra­tional study, Gen­er8-1 with the 6e13 dose to demon­strate ben­e­fits well be­yond pro­phy­lac­tic fac­tor use.” said Hank Fuchs, pres­i­dent, world­wide re­search and de­vel­op­ment at Bio­Marin.

The 6e13 vg/kg co­hort saw no spon­ta­neous bleeds and elim­i­na­tion of all bleeds in tar­get joints in the sec­ond year. And 71% and 86% of par­tic­i­pants had ze­ro bleeds re­quir­ing Fac­tor VI­II in­fu­sions in years 1 and 2 re­spec­tive­ly com­pared to 14% who had ze­ro bleeds re­quir­ing Fac­tor VI­II in­fu­sions for a year at base­line. There was a 96% re­duc­tion in mean FVI­II us­age through week 104. Qual­i­ty of life as mea­sured by the six-do­main Haemo-QoL-A in­stru­ment rapid­ly im­proved across all do­mains by up to 17.3 points in mean over base­line through the sec­ond year. 

Not­ed Bio­Marin: “This is well above the 5.2 point in­crease con­sid­ered to be the min­i­mal clin­i­cal­ly im­por­tant dif­fer­ence.”

An­a­lysts, though, high­light­ed some con­cerns with the ther­a­py’s abil­i­ty to keep fac­tor lev­els run­ning at a con­sis­tent lev­el, some­thing no gene ther­a­py de­vel­op­er wants to see. Leerink’s Joseph Schwartz picked out some sore points:

In the midst of to­day’s up­date, we be­lieve in­vestors will take is­sue with at least 2 points in the da­ta – 1) the grad­ual de­cline in FVI­II lev­els (breach­ing low­er bound of nor­mal on me­di­an FVI­II), and 2) Haemo-QoL gap down – gap up both be­fore and af­ter week 52. To the first point, mgmt. ref­er­enced pre­clin­i­cal ev­i­dence as well as the bi­ol­o­gy of gene ex­pres­sion to sug­gest a sta­ble plateau may have been achieved. Up­on fur­ther ob­ser­va­tion, it ap­pears the ma­jor gap down oc­curred be­tween weeks 78 and 91 lead­ing to the ma­jor­i­ty of pts. ex­hibit­ing nor­mal lev­els of FVI­II (50-150 IU/dL) by week 104. It is not ex­act­ly clear what trig­gered the drop, or whether this de­crease was an anom­aly (e.g., dri­ven by 1-2 pts.); how­ev­er, we would ex­pect to see con­tin­ued per­sis­tence of ~50 IU/dL lev­el in sub­se­quent up­dates po­ten­tial­ly at the Amer­i­can So­ci­ety of Hema­tol­ogy (ASH) by YE18. As for the sud­den drop in Haemo-QoL, mgmt. clar­i­fied that the week 52-78 dy­nam­ic was dri­ven by ex­tra­or­di­nary cir­cum­stances in 1 pt. (in­clud­ing job loss and a pre-planned knee re­place­ment). Over­all, dri­ven by a broad im­pact (i.e., across all six do­mains of the as­sess­ment), mgmt. is op­ti­mistic that the pos­i­tive ef­fects seen across clin­i­cal end­points are al­so ben­e­fit­ing pt. QoL.

Bio­Marin’s shares slid 4% mid-day on the wor­ries.

Bio­Marin has high hopes for this ther­a­py, a bell­wether treat­ment in a mix of drugs be­ing po­si­tioned to take the he­mo­phil­ia mar­ket by storm. Its progress on he­mo­phil­ia A comes a year af­ter Pfiz­er struck a pricey deal with Sang­amo to use its zinc fin­ger tech to make a ri­val — though Bio­Marin re­mains well in front. The Sang­amo team dosed their first pa­tient last fall, while Bio­Marin has two years of da­ta on some pa­tients.

In the mean­time, Bio­Marin is wait­ing out the clock on its May 25 PDU­FA dead­line for peg­valiase, which it hopes will soon be­come its 7th mar­ket­ed drug.


Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

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

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.