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.

 

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

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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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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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.

Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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New safe­ty da­ta ex­pose po­ten­tial weak­ness as Pfiz­er's abroc­i­tinib takes on Dupix­ent in eczema

Last September, when Pfizer celebrated positive data from a second Phase III study of abrocitinib, many watchers applauded the efficacy but were still waiting to see whether the JAK1 inhibitor is “safe enough to be a formidable competitor to Dupixent,” the clear leader in the atopic dermatitis field. The full slate of safety data are now out and, according to one analyst, the answer is: probably not.