Be­lea­guered Zaf­gen crushed af­ter FDA de­mands force it to dump lead drug

Stymied at the FDA with a lin­ger­ing clin­i­cal hold on its lead obe­si­ty drug, Zaf­gen is dump­ing the ther­a­py and re­treat­ing to a pre­clin­i­cal pro­gram in the pipeline.

The biotech an­nounced af­ter the mar­ket closed on Tues­day that it will now cir­cle the wag­ons around ZGN-1061 af­ter be­lo­ranib was linked with the death of two pa­tients in a piv­otal study. Zaf­gen al­so says it will once again re­duce its ranks, chop­ping 34% of the sur­vivors and cut­ting the pay­roll to 31. The re­or­ga­ni­za­tion is claim­ing the jobs of Patrick Lous­tau, pres­i­dent, and Ali­cia Sec­or, chief com­mer­cial of­fi­cer.

Zaf­gen’s al­ready bat­tered shares plunged 50% by mid-morn­ing Wednes­day. Its shares have shed close to 90% of their 52-week high price, leav­ing the mar­ket cap at $93 mil­lion; less than the cash it has on hand.

Zaf­gen strug­gled might­i­ly for months to over­come its prob­lems, but ul­ti­mate­ly the biotech was over­whelmed af­ter a pa­tient died in their Phase III study for Prad­er-Willi syn­drome, which they de­ter­mined was caused by a pul­monary em­bolism. Sub­se­quent­ly an­oth­er pa­tient tak­ing the drug died, al­so from a pul­monary em­bolism, forc­ing the FDA to or­der a com­plete stop to any fur­ther dos­ing.

Zaf­gen cut its near-com­plete stud­ies short, rolling out pos­i­tive da­ta on weight loss and re­fo­cus­ing on rare dis­eases, but it was all for naught. Reg­u­la­tors weren’t in a for­giv­ing mood, or ready to let the de­vel­op­ment pro­gram con­tin­ue the way the biotech had pro­posed. The FDA didn’t fall­en in line with Zaf­gen’s plan to blaze a path for­ward with a new Phase III study tied to a risk mit­i­ga­tion strat­e­gy. In a call with an­a­lysts on Tues­day evening, CEO Tom Hugh­es said that while the agency ap­peared re­cep­tive to its risk mit­i­ga­tion strat­e­gy, reg­u­la­tors de­mand­ed more time for dis­cus­sion and looked for a longer Phase III that would “great­ly ex­tend” the time­line and cost need­ed to be­gin com­mer­cial­iza­tion work.

As is of­ten the case with Zaf­gen, ex­ecs spun the news hard, with Hugh­es dogged­ly in­sist­ing on the pos­i­tive as­pects of start­ing with a clean slate and a new drug. But Zaf­gen is mov­ing from a piv­otal stage back to a pre­clin­i­cal drug that has yet to be test­ed in hu­mans. Hugh­es in­sist­ed that 1061, which has on­ly been test­ed in an­i­mals, is sig­nif­i­cant­ly de-risked, a po­si­tion few ex­pe­ri­enced drug de­vel­op­ers would con­sid­er plau­si­ble, giv­en the ex­tra­or­di­nar­i­ly high rate of fail­ure for all pre­clin­i­cal pro­grams, let alone the spe­cial de­mands placed on any obe­si­ty drug.

Zaf­gen will still have to con­tend with an­gry in­vestors who watched the share price for the biotech plunge last year as com­pa­ny ex­ec­u­tives re­fused for sev­er­al days to say just why they had can­celled a planned road show. On­ly af­ter a pro­longed pause did the com­pa­ny re­veal that first death, still try­ing to de­ter­mine whether he was in the drug arm or the place­bo group. Sahm Ad­ran­gi’s Ker­ris­dale Cap­i­tal lat­er mount­ed a short at­tack on the wound­ed com­pa­ny, say­ing that be­lo­ranib had ze­ro chance of ever get­ting an ap­proval and was worth noth­ing more than what the com­pa­ny had in the bank, which they would prob­a­bly squan­der any­way.

An­a­lysts were left to sort through the wreck­age Wednes­day morn­ing. RBC’s Simos Sime­oni­dis de­cid­ed to dis­con­tin­ue cov­er­age of Zaf­gen and oth­er obe­si­ty-re­lat­ed biotechs — which have seen lit­tle that could be con­sid­ered pos­i­tive news in some time — and some oth­er skep­tics ad­just­ed their fore­casts for Zaf­gen’s shares to match the amount of cash the com­pa­ny still has in hand.

CEO Tom Hugh­es’ state­ment:

“Giv­en the height­ened com­plex­i­ty and fu­ture cost of be­lo­ranib de­vel­op­ment, bal­anced against the emerg­ing prod­uct pro­file of ZGN-1061, we be­lieve that the long-term op­por­tu­ni­ty for ZGN-1061 is more ro­bust than for be­lo­ranib. Giv­en our deep knowl­edge of this new and ex­cit­ing drug class, and our strong cash po­si­tion, we be­lieve we are well-po­si­tioned to ad­vance ZGN-1061 as a po­ten­tial new treat­ment for preva­lent obe­si­ty-re­lat­ed in­di­ca­tions.”

Amarin CEO John Thero discussing the company's plans for Vascepa, August 2019 — via Bloomberg

Amarin wins a block­buster ap­proval from the FDA. Now every­one can shift fo­cus to the patent

For all those people who could never quite believe that Amarin $AMRN would get an expanded label with blockbuster implications, the stress and anxiety on display right up to the last minute on Twitter can now end. But new, pressing questions will immediately surface now that the OK has come through.

On Friday afternoon, the FDA stamped its landmark approval on the industrial strength fish oil for reducing cardio risks for a large and well defined population of patients. The approval doesn’t give Amarin everything it wants in expanding its use, losing out on the primary prevention group, but it goes a long way to doing what the company needed to make a major splash. The approval was cited for patients with “elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease.”

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Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Sarep­ta was stunned by the re­jec­tion of Vyondys 53. Now it's stun­ning every­one with a sur­prise ac­cel­er­at­ed ap­proval

Sarepta has a friend in the FDA after all. Four months after the agency determined that it would be wrong to give Sarepta an accelerated approval for their Duchenne MD drug golodirsen, regulators have executed a stunning about face and offered the biotech a quick green light in any case.

It was the agency that first put out the news late Thursday, announcing that Duchenne MD patients with a mutation amenable to exon 53 skipping will now have their first targeted treatment: Vyondys 53, or golodirsen. Having secured the OK via a dispute resolution mechanism, the biotech said the new drug has been priced on par with their only other marketed drug, Exondys 51 — which for an average patient costs about $300,000 per year, but since pricing is based on weight, that sticker price can even cross $1 million.

Sarepta shares $SRPT surged 23% after-market to $124.

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Arie Belldegrun (Photo: Jeff Rumans for Endpoints News)

Ju­ry finds Gilead li­able for $585M and big roy­al­ties in Kite CAR-T patent case

A Kite deal that’s already become a burden on Gilead’s back just got heavier as a California jury has ruled Gilead must pay Bristol-Myers Squibb and Sloan Kettering $585 million plus a 27.6% royalty for patent infringement committed by its subsidiary. The ruling is almost certain to be appealed.

Kite Pharma — founded by Arie Belldegrun, now focused on a next-gen CAR-T company — has been facing a lawsuit since the day its first CAR–T therapy won approval in October, 2017. Juno Therapeutics and Sloan Kettering filed a complaint saying Kite had copied its technology. Gilead acquired Kite in June of that year for $11.9 billion.  Juno was acquired the following year by Celgene for $9 billion, before Celgene was acquired by Bristol-Myers Squibb in 2019.

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FDA ex­pert pan­el unan­i­mous­ly rec­om­mends ap­proval for Hori­zon Ther­a­peu­tics eye drug

An FDA advisory committee noted with concern a small safety database but unanimously endorsed a Horizon Therapeutics drug for a rare eye autoimmune disease that can blind patients: teprotumumab for thyroid eye disease (TED).

“It was a pretty easy vote,” said Erica Brittain, an NIH biostatistician and one of the 12 panelists on FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee.

This image shows a lab technician measuring the zone of inhibition during an antibiotic sensitivity test, 1972. The zone of inhibition is measured and compared to a standard in order to determine if an antibiotic is effective in treating the bacterial infection. (Gilda Jones/CDC via Getty Images)

Bio­phar­ma has aban­doned an­tibi­ot­ic de­vel­op­ment. Here’s why we did, too.

Timing is Everything
When we launched Octagon Therapeutics in late 2017, I was convinced that the time was right for a new antibiotic discovery venture. The company was founded on impressive academic pedigree and the management team had known each other for years. Our first program was based on a compelling approach to targeting central metabolism in the most dangerous bacterial pathogens. We had already shown a high level of efficacy in animal infection models and knew our drug was safe in humans.

Shehnaaz Suli­man dives back in­to Alzheimer's at Alec­tor; Pyx­is re­cruits Spring­Works founder Lara Sul­li­van as CEO

Amid Shehnaaz Suliman’s lengthy resume it could be easy to miss her stint leading early-stage Alzheimer’s R&D at Genentech, where she oversaw a program for the ill-fated crenezumab and initiated one of the first prevention studies around the devastating neurodegenerative disease. But it is this experience that she — after thinking long and hard about her next career move over the past months — will be leaning heavily on as the first president and COO of Alector.

PhII fail­ure in rare neu­rode­gen­er­a­tive dis­ease? No mat­ter, Bio­gen will mo­tor on in Alzheimer's

Biogen’s fierce focus on disorders of the brain has hit another roadblock.

On Friday, the US drugmaker — which recently resurrected its amyloid-targeting Alzheimer’s drug, aducanumab — said its anti-tau drug, gosuranemab, failed a mid-stage study in patients with progressive supranuclear palsy (PSP), a rare brain disorder that results from deterioration of brain cells that control movement and thought.

Paul Biondi (File photo)

Paul Biondi's track record at Bris­tol-My­ers cov­ered bil­lions in deals of every shape and size. Here's the com­plete break­down

Paul Biondi was never afraid to bet big during his stint as business development chief at Bristol-Myers Squibb. And while the gambles didn’t all pay out, by any means, his roster of pacts illustrates the broad ambitions the pharma giant has had over the last 5 years — capped by the $74 billion Celgene buyout.

On Thursday, we learned that Biondi had exited the company. And Chris Dokomajilar at DealForma came up with the complete breakdown on every buyout, licensing pact and product purchase Bristol-Myers forged during his tenure in charge of the BD team at one of the busiest companies in biopharma.

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