Their lead drug failed both main goals in key study, but Or­p­hazyme plans to pitch sub­group analy­ses to reg­u­la­tors

Or­p­hazyme at­tempt­ed on Wednes­day to en­thuse in­vestors about the re­sults of a Phase II/III study test­ing their lead drug, ari­mo­clo­mol, in pa­tients with a rare ge­net­ic dis­or­der, un­der­scor­ing some pos­i­tive sub­group analy­ses — even though the ex­per­i­men­tal treat­ment missed its pri­ma­ry end­points. The com­pa­ny is now prepar­ing mar­ket­ing fil­ings and plan­ning to en­gage with reg­u­la­tors to get ari­mo­clo­mol on the mar­ket at the ear­li­est.

The com­pa­ny’s shares (CPH: $OR­PHA) shot up about 40% in re­sponse on Wednes­day, but climbed down about 5% on Thurs­day af­ter­noon GMT.

The drug is be­ing eval­u­at­ed for use in Nie­mann-Pick dis­ease Type C (NPC), an in­her­it­ed neu­rode­gen­er­a­tive dis­ease char­ac­ter­ized by the body’s in­abil­i­ty to trans­port cho­les­terol and oth­er lipids in­side of cells that caus­es an ab­nor­mal ac­cu­mu­la­tion with­in var­i­ous tis­sues in­clud­ing the brain. In the 12-month study, 50 pa­tients be­tween the age of 2 and 18 were giv­en ei­ther ari­mo­clo­mol or place­bo on top of stan­dard of care.

The com­pa­ny high­light­ed sub­group analy­ses that sug­gest the drug has a sig­nif­i­cant im­pact on the dis­ease. But that comes af­ter the com­pa­ny ac­knowl­edged months ago that the drug failed the pri­ma­ry end­point.

An­ders Hins­by

“With this high­ly com­pelling da­ta set, we are look­ing for­ward to work­ing with reg­u­la­to­ry au­thor­i­ties to make ari­mo­clo­mol avail­able to pa­tients as fast as pos­si­ble,” Or­p­hazyme chief An­ders Hins­by said in a state­ment.

The tri­al had two pri­ma­ry end­points track­ing dis­ease pro­gres­sion: the 5-do­main NPC Clin­i­cal Sever­i­ty Scale (NPC-CSS), a dis­ease-spe­cif­ic out­come mea­sure, as well as Clin­i­cal Glob­al Im­pres­sion of Im­prove­ment scale (CGI-I), a self-rat­ing tool, at the be­hest of the FDA.

In terms of NPC-CSS, the com­pa­ny said treat­ment with ari­mo­clo­mol ad­junct to rou­tine clin­i­cal care re­sult­ed in a 74% re­duc­tion in dis­ease pro­gres­sion, but the p-val­ue at 0.0506 in­di­cat­ed the ef­fect was not sta­tis­ti­cal­ly sig­nif­i­cant. But re­searchers claimed that two sub­group analy­ses of­fered stronger con­vic­tion of the drug’s po­ten­tial ben­e­fit. When look­ing at pa­tients 4 years or old­er (44/50), treat­ment pro­gres­sion slowed in pa­tients on ari­mo­clo­mol ver­sus place­bo, with a p-val­ue of 0.0219. An­oth­er sub­group analy­sis, re­quest­ed by the EMA, showed that ari­mo­clo­mol had a sig­nif­i­cant im­pact com­pared to a place­bo in pa­tients who got miglu­s­tat — orig­i­nal­ly sold by Acte­lion un­der the brand name Za­vesca — as part of stan­dard care, with a p-val­ue of 0.0071.

On the CGI-I end­point, an in­flat­ed place­bo re­sponse de­terred the drug from demon­strat­ing an im­pact on the main goal, the com­pa­ny said, adding that when con­sid­er­ing pa­tients who se­vere­ly pro­gressed dur­ing the tri­al, on­ly 10.7% of ari­mo­clo­mol-treat­ed pa­tients got “much worse” or “very much worse” com­pared to 26.7% in the place­bo con­trol group.

Oth­er sub­group analy­ses al­so sug­gest­ed a lack of sta­tis­ti­cal sig­nif­i­cant im­prove­ment with the drug, al­though some ex­plorato­ry bio­mark­er da­ta were fa­vor­able to ari­mo­clo­mol.

Safe­ty da­ta were al­so pos­i­tive, with se­ri­ous side-ef­fects oc­cur­ring less fre­quent­ly in the ari­mo­clo­mol group (14.7%) com­pared to place­bo con­trol (37.5%).

The ball is now in the reg­u­la­to­ry court, but con­sid­er­ing NPC is a rare dis­ease af­fect­ing an es­ti­mat­ed in 1/120 000 live births, it could go ei­ther way.

Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

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Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

Boehringer Ingelheim’s BD team is on a global deal spree. The German pharma company just wrapped its third deal in 3 weeks, going back to Korea for its latest pipeline pact — this time focused on idiopathic pulmonary fibrosis.

They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

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Servi­er scoots out of an­oth­er col­lab­o­ra­tion with Macro­Gen­ics, writ­ing off their $40M

Servier is walking out on a partnership with MacroGenics $MGNX — for the second time.

After the market closed on Wednesday MacroGenics put out word that Servier is severing a deal — inked close to 7 years ago — to collaborate on the development of flotetuzumab and other Dual-Affinity Re-Targeting (DART) drugs in its pipeline.

MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.

Den­mark's Gen­mab hits the jack­pot with $500M+ US IPO as small­er biotechs rake in a com­bined $147M

Danish drugmaker Genmab A/S is off to the races with perhaps one of the biggest biotech public listings in decades, having reaped over $500 million on the Nasdaq, as it positions itself as a bonafide player in antibody-based cancer therapies.

The company, which has long served as J&J’s $JNJ key partner on the blockbuster multiple myeloma therapy Darzalex, has asserted it has been looking to launch its own proprietary product — one it owns at least half of — by 2025.

FDA over­rides ad­comm opin­ions a fifth of the time, study finds — but why?

For drugmakers, FDA advisory panels are often an apprehended barometer of regulators’ final decisions. While the experts’ endorsement or criticism often translate directly to final outcomes, the FDA sometimes stun observers by diverging from recommendations.

A new paper out of Milbank Quarterly put a number on that trend by analyzing 376 voting meetings and subsequent actions from 2008 through 2015, confirming the general impression that regulators tend to agree with the adcomms most of the time — with discordances in only 22% of the cases.

UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

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