A for­mer fail­ure in PhII, the go-go FDA says it’s ready to con­sid­er an ac­cel­er­at­ed short­cut for Ul­tragenyx's UX007

More than a year af­ter Ul­tragenyx $RARE an­nounced the fail­ure of a Phase II study for its seizure med­ica­tion UX007, the rare dis­ease spe­cial­ist says the FDA has now of­fered a thumbs-up for its will­ing­ness to con­sid­er an ac­cel­er­at­ed ap­proval for a dif­fer­ent in­di­ca­tion.

The biotech is pur­su­ing an OK for long-chain fat­ty acid ox­i­da­tion dis­or­ders af­ter piec­ing to­geth­er da­ta that spot­light­ed a drop in ma­jor clin­i­cal events for LC-FAOD.

As the com­pa­ny ex­plains, LC-FAOD rep­re­sents “a group of au­to­so­mal re­ces­sive ge­net­ic dis­or­ders char­ac­ter­ized by meta­bol­ic de­fi­cien­cies in which the body is un­able to con­vert long-chain fat­ty acids in­to en­er­gy.” With­out that, there’s a se­vere de­ple­tion of glu­cose that can cause hav­oc in a child. It’s cur­rent­ly treat­ed with an ul­tra-low carb ke­to­genic di­et, which is a com­mon ther­a­py for epilep­sy and seizures, where Ul­tragenyx orig­i­nal­ly looked for pos­i­tive da­ta.

An­a­lysts at JMP Se­cu­ri­ties not­ed a few days ago that in their con­ver­sa­tions with Ul­tragenyx ex­ecs, they made it clear that reg­u­la­tors had al­ready de­ter­mined the biotech’s mid-stage da­ta were “con­found­ed and not suf­fi­cient to pur­sue a fil­ing.”

Now, sud­den­ly, that’s all changed.

This ac­cel­er­ates our launch time­lines. Pre­vi­ous­ly, we con­ser­v­a­tive­ly mod­eled a U.S. launch in 2021 which we now be­lieve could come as ear­ly as 2020. Ul­tragenyx an­tic­i­pates a pre-NDA meet­ing in 2H18 af­ter which it will pro­vide ad­di­tion­al de­tails; in the mean­time, we es­ti­mate a sub­mis­sion in 1H2019.

Emil Kakkis, Ul­tragenyx

The ear­li­er mid-stage fail­ure was plain. UX007 is a drug de­signed to ad­dress glu­cose trans­porter type-1 de­fi­cien­cy syn­drome — or Glut1 DS — in chil­dren by get­ting glu­cose in­to the brains of the ge­net­i­cal­ly af­flict­ed group. With­out the right lev­el of glu­cose, pa­tients have a ten­den­cy to ex­pe­ri­ence re­peat­ed seizures. 

In the study, the drug didn’t work. Track­ing ob­serv­able as well as “ab­sence seizures,” a tem­po­rary loss of at­ten­tion of­ten marked by a dis­tant stare, re­searchers record­ed an unim­pres­sive 13.4% re­sponse rate in over­all seizure fre­quen­cy (p=0.41) among 25 pa­tients in the drug arm and 11 in the place­bo group. That was the pri­ma­ry end­point.


If you take out the more se­vere ob­serv­able seizure rate and con­cen­trate on a sec­ondary end­point for the so-called ab­sence seizures, the drug sparked a 47% drop in their small group. And that was sta­tis­ti­cal­ly sig­nif­i­cant.

In their state­ment to­day, the biotech says that they cob­bled to­geth­er a va­ri­ety of da­ta that was avail­able, high­light­ing a sig­nif­i­cant drop in “the mean an­nu­al­ized rate of ma­jor clin­i­cal events.”

The FDA un­der Scott Got­tlieb has re­peat­ed­ly sig­naled their will­ing­ness to ex­am­ine new ap­proach­es to short­en­ing the time­line on drug de­vel­op­ment. And Ul­tragenyx says it will be ready to roll if they get a green light.

Shares of Ul­tragenyx, which has en­joyed a cou­ple of key ap­provals, are up 3% in pre-mar­ket trad­ing.

“We ap­pre­ci­ate FDA’s re­view of mul­ti­ple da­ta sub­mis­sions and col­lab­o­ra­tion with us to de­vel­op a path for an ear­ly fil­ing, and it is our com­mit­ment to get this im­por­tant po­ten­tial treat­ment to pa­tients with this se­ri­ous dis­ease as quick­ly as pos­si­ble,” said Emil D. Kakkis, the CEO of Ul­tragenyx. “We will meet with the FDA to dis­cuss the de­tails of the NDA sub­mis­sion and, if ap­proved, ap­pro­pri­ate post-ap­proval com­mit­ments to fur­ther eval­u­ate long-term out­comes of UX007 in pa­tients with LC-FAOD.” 

Im­age: YouTube

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.

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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.

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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.

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.

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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.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.