FDA slaps par­tial hold on Macro­Gen­ics for bis­pe­cif­ic can­cer tri­als as liv­er tox spurs safe­ty fears

Leery about signs of liv­er tox­i­c­i­ty among pa­tients tak­ing a B7-H3 × CD3 bis­pe­cif­ic un­der de­vel­op­ment at Macro­Gen­ics $MGNX, the FDA has slapped a par­tial hold on the ear­ly-stage pro­gram.

The par­tial hold — which af­fects their monother­a­py tri­al as well a com­bi­na­tion ef­fort with their own PD-1 check­point MGA012, part­nered with In­cyte — will stop re­searchers from re­cruit­ing new pa­tients, but peo­ple who have al­ready signed up can con­tin­ue treat­ment.

Scott Koenig

Macro­Gen­ics was quick to down­play the move, not­ing that signs of el­e­vat­ed transam­i­nas­es in the sin­gle-drug study were quick­ly re­solved. And the biotech got some quick help from an­a­lysts, who haven’t been pay­ing all that much at­ten­tion to this pro­gram’s par­tic­u­lar po­ten­tial. CD3, though, plays a promi­nent role in some lead­ing bis­pe­cif­ic ef­forts, and the an­a­lysts would like to know more if the prob­lem here may ex­tend to oth­er de­vel­op­ers.

Macro­Gen­ics has been test­ing this bis­pe­cif­ic in pa­tients with non-small cell lung, blad­der and head and neck can­cer, mesothe­lioma, melanoma, and oth­er B7-H3 pos­i­tive tu­mors.

Jonathan Chang

Leerink’s Jonathan Chang passed along man­age­ment’s con­fi­dence that it can get past this hitch in short or­der and has al­ready pitched a new plan to boost sup­port­ive care in the tri­als.

Over­all, man­age­ment seemed bull­ish that the par­tial clin­i­cal hold could be lift­ed as ear­ly as Jan­u­ary 2019 based on the reg­u­la­to­ry dis­cus­sions so far and the changes be­ing pro­posed, in our view. Man­age­ment in­di­cat­ed that liv­er func­tion test (LFT) el­e­va­tions were ini­tial­ly ob­served in the Q2 week­ly dos­ing reg­i­men, which re­solved with a re­duc­tion in dose. How­ev­er, LFT el­e­va­tions were then ob­served in a cou­ple more pa­tients at a low­er dose.

Umer Raf­fat at Ever­core ISI is in the group that wants to learn more AS­AP.

We sus­pect the liv­er tox in the B7-H3 x CD3 DART may be ON-tar­get tox of this spe­cif­ic com­bi­na­tion. Al­though the com­pa­ny says B7-H3 ex­pres­sion is high in sol­id tu­mors and min­i­mal in nor­mal tis­sues, oth­er sources (see an im­age from the Hu­man Pro­tein At­las at bot­tom) sug­gest B7-H3 (aka CD276) has medi­um to high ex­pres­sion in var­i­ous tis­sues, in­clud­ing the liv­er… If nor­mal cells al­so ex­press B7-H3, then this DART may in­duce more im­mune ac­ti­va­tion than ex­pect­ed, in non-tu­mor en­vi­ron­ments like the liv­er. This is just a hy­poth­e­sis, and we need to see fur­ther clin­i­cal da­ta on safe­ty – it’s hard to make a de­fin­i­tive call giv­en the lim­it­ed de­tail we’ve seen thus far.

“As we’ve iden­ti­fied to the FDA, we be­lieve that transamini­tis ob­served in pa­tients ad­min­is­tered MGD009 was like­ly a cy­tokine-me­di­at­ed event,” not­ed CEO Scott Koenig in a state­ment. “We are work­ing with the FDA and will pro­vide an up­date when we have ad­di­tion­al in­for­ma­tion. This par­tial clin­i­cal hold does not im­pact on­go­ing clin­i­cal stud­ies for enobli­tuzum­ab and MGC018, our oth­er B7-H3-tar­get­ed mol­e­cules.”

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.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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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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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).

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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