Ab­b­Vie’s PARP in­hibitor floun­ders in PhII as ri­vals surge ahead in late-stage dri­ve

Heather S. Han, Mof­fitt Can­cer Cen­ter

Ab­b­Vie’s PARP in­hibitor veli­parib failed two key end­points in a Phase II study of metasta­t­ic breast can­cer with BR­CA1 or BR­CA2 mu­ta­tions.

In­ves­ti­ga­tors, in­clud­ing Heather Han from Mof­fitt, turned up at the San An­to­nio Breast Can­cer Sym­po­sium to re­port that the pro­gres­sion-free sur­vival rate of veli­parib com­bined with car­bo­platin and pa­cli­tax­el chemother­a­py was 14.1 months, an im­prove­ment but not a sta­tis­ti­cal­ly sig­nif­i­cant ad­vance when you com­pared the 12.3-month PFS rate in the group that sub­sti­tut­ed a place­bo for veli­parib. The over­all sur­vival rate — 28.3 months ver­sus 25.9 months — al­so failed to suf­fi­cient­ly di­verge.

The PARP race has been at­tract­ing con­sid­er­able at­ten­tion this year, es­pe­cial­ly af­ter Pfiz­er stepped in to buy Medi­va­tion and its late-stage PARP in a $14 bil­lion deal. Just weeks ago As­traZeneca whet in­vestors ap­petites when it said its Phase III study has pro­duced sol­id sup­port­ing da­ta. Tesaro and Clo­vis, mean­while, are al­so rac­ing for an ap­proval.

Ab­b­Vie’s ri­val, though, is much fur­ther back in the pack, and won’t get many peo­ple talk­ing with da­ta like this. Han said that the prob­lem with the Phase II study is that it wasn’t de­signed to care­ful­ly track non­dra­mat­ic dif­fer­ences. There’s a Phase III un­der­way now that they be­lieve will come up with the goods.

I asked Ab­b­Vie how the com­pa­ny ex­pects to emerge on top giv­en a busy field of ad­vanced con­tenders and the failed Phase II. Dr. Vince Gi­ran­da, project di­rec­tor, Ab­b­Vie On­col­o­gy De­vel­op­ment, an­swered as fol­lows:

I would first like to pro­vide an ex­pla­na­tion of the cur­rent clin­i­cal tri­als de­sign.  The phase 2 tri­al was de­signed as a sig­nal gen­er­a­tion tri­al.  The on­go­ing phase 3 tri­al was de­signed to be adapt­ed to the size of the sig­nal we have ob­served in phase 2, es­sen­tial­ly to en­sure the num­ber of pa­tients in the phase 3 tri­al is suf­fi­cient to test the hy­poth­e­sis. The pos­i­tive trends in OS, PFS and ORR ob­served in the phase 2 tri­al were of suf­fi­cient mag­ni­tude to war­rant con­tin­u­a­tion of the phase 3 tri­al.  If we had de­signed the phase 2 tri­al to be sta­tis­ti­cal­ly sig­nif­i­cant it would have been a piv­otal tri­al, and there would be no need to start the on­go­ing phase 3 tri­al.

In in­stances where a nov­el agent (e.g. veli­parib) is com­bined with an ac­tive agent (e.g. car­bo­platin) a ran­dom­ized, blind­ed, and place­bo con­trolled tri­al is one of the best meth­ods by which to de­ter­mine if ad­di­tion of a nov­el agent pro­vides a ben­e­fit. The re­sults of the small phase 2 tri­al are then as­sessed to de­ter­mine if there is a sig­nal of po­ten­tial ac­tiv­i­ty.  In ad­di­tion, if the po­ten­tial sig­nal is ob­served, it pro­vides the ba­sis for de­ter­min­ing the ap­pro­pri­ate size of the phase 3 tri­al.

Di­rect­ly re­spond­ing to your ques­tion, our re­search on veli­parib is fo­cused on use in com­bi­na­tion with plat­inum based chemother­a­py, which ap­pears to pro­duce high re­sponse rates in BR­CA-as­so­ci­at­ed breast can­cers. This is the first Phase 2 ran­dom­ized study to show that a PARP in­hibitor has the po­ten­tial to en­hance the ef­fi­ca­cy of plat­inum chemother­a­py. This fo­cus is dis­tinct from oth­er late-stage clin­i­cal PARP in­hibitors that are fo­cused on treat­ing BR­CA breast can­cer with­out ad­di­tion of plat­inum-based chemother­a­py.


On the heels of promis­ing MCL da­ta, Kite hus­tles its 2nd CAR-T to the FDA as the next big race in the field draws to the fin­ish line

Three days after Gilead’s Kite subsidiary showed off stellar data on their number 2 CAR-T KTE-X19 at ASH, the executive team has pivoted straight to the FDA with a BLA filing and a shot at a near-term approval.

In a small, 74-patient Phase II trial reported out at the beginning of the week, investigators tracked a 93% response rate with two out of three mantle cell lymphoma patients experiencing a complete response.

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Paul Hudson, Getty Images

UP­DAT­ED: 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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Cor­re­vio is putting it­self up on the auc­tion block af­ter FDA re­view pan­el points to an­oth­er re­jec­tion

For 13 years, the Canadian biotech Correvio tried to get the FDA to accept a heart drug since abandoned by Merck and Astellas. Yesterday, the agency’s outside experts voted 11-2 against approval, all but assuring another rejection for the atrial fibrillation compound vernakalant.

And today Correvio announced that Correvio may soon be no more. The company said it is looking to sell itself as its stock plummets into penny-stock territory $CORV and its potential moneymaker sputters once more.

Psilocybin mushrooms (via The Denver Post)

In a key step for psy­che­del­ic re­search, mag­ic mush­room com­pound clears first clin­i­cal safe­ty hur­dle

Exasperated with the often-ineffective existing slate of antidepressants, COMPASS Pathways set up shop in London 2016 — and made a beeline for psilocybin, the psychoactive ingredient in magic mushrooms.

On Wednesday, the startup said its man-made version of the chemical — which is illegal across geographies in its natural fungi form — had been well-tolerated in an early-stage, placebo-controlled trial in 89 healthy volunteers.

Al­pham­ab On­col­o­gy rounds out HKEX's sec­ond biotech IPO year with $230M raise and high lo­cal in­ter­est

Alphamab Oncology has inspired a surge of local interest in what will likely be the Hong Kong Stock Exchange’s last biotech run of the year, pricing its IPO on the high end of the range and raising over $230 million (HK$1.83 billion).

After rejigging the offering structure and making up to 50% available for enthusiastic local investors, the biotech sold 179.4 million shares at $1.31 (HK$10.2) and saw its stock rise to $1.77 ($13.8) on the first day of trading.

For sale: Long-act­ing PhI­II GLP-1 di­a­betes drug that’s way be­hind ri­vals, now spurned by Sanofi

Almost exactly 4 years ago Sanofi came to the bargaining table with South Korea’s Hanmi bearing $434 million dollars in cash and offering about $4 billion in milestones to in-license their once-weekly GLP-1 injectable. The pact was intended to revive their ailing diabetes division. Instead, it turned into a very expensive grave to mark the end of Sanofi’s R&D ambitions in the field.

Sanofi CEO Paul Hudson used efpeglenatide’s demise — while committing to paying hundreds of millions of more dollars to push it through 5 late-stage studies — as a marker of the company’s determination to stay focused on first and best-in-class drugs.

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What does $6.9B buy these days in on­col­o­gy R&D? As­traZeneca has a land­mark an­swer

Given the way the FDA has been whisking through new drug approvals months ahead of their PDUFA date, AstraZeneca and their partners Daiichi Sankyo may not have to wait until Q2 of next year to get a green light on trastuzumab deruxtecan (DS-8201).

The pharma giant this morning played their ace in the hole, showing off why they were willing to commit to a $6.9 billion deal — with $1.35 billion in a cash upfront — to partner on the drug.

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Parkin­son's trans­plants emerge as stem cell pi­o­neer Jeanne Lor­ing joins R&D race

Jeanne Loring hadn’t studied Parkinson’s in 22 years when she got an email from a local neurologist.

The neurologist, Melissa Houser, didn’t know Loring had ever published on the disease. She was just looking for a stem cell researcher who might hear her out. 

“I think I was just picked out of a hat,” Loring told Endpoints News. 

At a meeting in Loring’s Scripps Research office, Houser and a Parkinson’s nurse practitioner, Sherrie Gould, asked her why there was so much research done in stem cell transplants for other neurodegenerative diseases but not Parkinson’s. They wanted to know if she would work on one. 

Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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