Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA fi­nal­ly grant­ed an ac­cel­er­at­ed OK for Im­munomedics’ Trodelvy, we al­ready got a very strong hint that their con­fir­ma­to­ry Phase III study in metasta­t­ic triple-neg­a­tive breast can­cer was a suc­cess.

That’s be­cause the in­de­pen­dent da­ta safe­ty mon­i­tor­ing com­mit­tee rec­om­mend­ed that the tri­al be stopped ear­ly. But just what point­ed them to the con­clu­sion was still un­clear.

Be­hzad Ag­haz­adeh

“We do not know the to­tal­i­ty of their de­ci­sion oth­er than it’s pret­ty ev­i­dent that the pri­ma­ry end­point was met; oth­er­wise they could not re­quest to halt the study,” Be­hzad Ag­haz­adeh, the ex­ec­u­tive chair­man, told End­points News at the time.

Three months lat­er, Im­munomedics has de­tailed the re­sults from AS­CENT, in­clud­ing pro­gres­sion-free sur­vival and over­all sur­vival da­ta that the prin­ci­pal in­ves­ti­ga­tor said “set a new bench­mark” in mTNBC.

PFS was the pri­ma­ry end­point, and Trodelvy — an an­ti­body-drug con­ju­gate known as sac­i­tuzum­ab govite­can — kept the can­cer at bay (and pa­tients from dy­ing) for a me­di­an of 5.6 months, com­pared to 1.7 months on chemother­a­py (p<0.0001). The haz­ard ra­tio reg­is­tered at 0.41.

Shares $IM­MU rose 6.67% to $40.04.

Im­munomedics stopped short of spelling out the OS win, but not­ed that and oth­er key sec­ondary end­points such as ob­jec­tive re­sponse rate were met.

Aditya Bar­dia

“Im­por­tant­ly, the AS­CENT topline da­ta al­so val­i­date the man­age­able safe­ty pro­file of sac­i­tuzum­ab govite­can, ren­der­ing it a good part­ner can­di­date for com­bi­na­tion with oth­er ther­a­pies, in­clud­ing im­munother­a­py,” Aditya Bar­dia, the prin­ci­pal in­ves­ti­ga­tor and di­rec­tor of pre­ci­sion med­i­cine at Mass Gen­er­al’s Cen­ter for Breast Can­cer, said.

Trodelvy was ap­proved, with a black box warn­ing for se­vere neu­trope­nia and se­vere di­ar­rhea, as a third-line treat­ment for mTNBC, a tough-to-treat can­cer as­so­ci­at­ed with poor prog­no­sis. The new da­ta are ex­pect­ed to sup­port a full OK.

“It is grat­i­fy­ing to see the fi­nal con­fir­ma­to­ry re­sults of Trodelvy in a ran­dom­ized study sup­port­ing the pre­vi­ous­ly re­port­ed Phase 2 da­ta that formed the ba­sis of the ac­cel­er­at­ed ap­proval of Trodelvy,” Ag­haz­adeh, who has been run­ning the show since Michael Pehl left the helm ear­ly 2019 in the wake of an FDA re­jec­tion, said in a state­ment.

No­var­tis On­col­o­gy vet and Ipsen alum Harout Se­mer­jian came on board briefly as CEO in April, on­ly to de­part less than two months lat­er as the pan­dem­ic cre­at­ed in­sur­mount­able chal­lenges for mov­ing his fam­i­ly from Lon­don.

The hic­cup hasn’t dent­ed Cowen an­a­lyst Phil Nadeau’s high ex­pec­ta­tions of the ther­a­py, which his con­sul­tants said will be rapid­ly adopt­ed as the stan­dard in re­lapsed or re­frac­to­ry mTNBC, bring­ing in $1 bil­lion in world­wide rev­enue by 2025 (Ever­est Med­i­cines is han­dling the de­vel­op­ment and com­mer­cial­iza­tion in Chi­na). Ac­cord­ing to Nadeau, the num­bers hit the “up­per end of ex­pec­ta­tions.”

“In­vestors an­tic­i­pat­ed that Trodelvy would pro­duce a me­di­an PFS of 5-5.5 months con­sis­tent with its Ph. I/II, but our sense is that most an­tic­i­pat­ed a me­di­an PFS for chemother­a­py of 2.5-3 months,” he wrote.

And that’s not tak­ing in­to ac­count its po­ten­tial in ER+/HER2- metasta­t­ic breast can­cer or urothe­lial car­ci­no­ma, which now seems even more like­ly giv­en the pos­i­tive AS­CENT da­ta.

“In­vestors un­der­es­ti­mate the sales po­ten­tial of Trodelvy,” he wrote in a re­cent note. “Trodelvy’s da­ta sug­gest it is a sim­i­lar im­prove­ment over the stan­dard of care in r/r ER+/HER2- mBC as it is in mTNBC, and there are ap­prox. 3-4x as many women with r/r ER+/HER2- mBC. This mar­ket is a $3-4B op­por­tu­ni­ty for Trodelvy, not yet ful­ly re­flect­ed in es­ti­mates or in IM­MU’s val­u­a­tion, de­spite po­ten­tial­ly piv­otal da­ta an­tic­i­pat­ed around YE.”

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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UP­DAT­ED: CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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David Hung (file photo)

Mas­ter deal­mak­er David Hung re­tools a SPAC sedan in­to a fi­nanc­ing mus­cle ve­hi­cle that leaves his can­cer start­up with $850M and a place on Wall Street

It’s only right that one of the industry’s top dealmakers just completed one of the biggest SPAC-related deals in the pipeline.

David Hung, of Medivation fame, has completed a back flip into the market, merging with EcoR1 Capital’s SPAC Panacea and landing neatly on Wall Street with an $NUVB stock ticker after filling out the blank check in his name. In addition to the $144 million held in the SPAC — provided none of the investors opt out — Hung is getting ahold of $500 million more being chipped in by a slate of institutional investors who feel that Hung could have the keys to another Medivation-style success.

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Years af­ter a ma­jor tri­al set­back, No­var­tis switch­es gears with SMA drug. This time they're try­ing it for Hunt­ing­ton's

Four years after a Phase I/II setback in spinal muscular atrophy (SMA), Novartis is hoping its drug branaplam will find more success in a new neurological indication: Huntington’s disease.

The decision was announced a year after the head of research, Jay Bradner, said he did not see a “big opportunity” in SMA, according to Reuters. Novartis says it has preclinical data showing that branaplam reduces levels of mutant huntingtin protein, and SMA data showing patients on the drug had reductions in huntingtin mRNA. The FDA gave branaplam their orphan drug designation, and Novartis plans to move forth with a Phase IIb trial next year.

Glax­o­SmithK­line's vac­cines group aims for a first as it kicks off PhI­II RSV stud­ies

One of GlaxoSmithKline’s big projects at its global vaccine R&D center in Rockville, MD is set to enter Phase III after passing early-stage tests with flying colors.

Eyeing the wide-open respiratory syncytial virus (RSV) space, GSK is pushing two different vaccine candidates: GSK3888550A is designed to confer protection to infants via maternal immunization, while GSK3844766A is meant for the elderly.

Roche finds a home for a new, $500M man­u­fac­tur­ing lo­gis­tics hub, promis­ing 500 jobs

Roche is pouring $500 million into its Canadian headquarters in Mississauga, Ontario to set up a new hub that will coordinate logistics for its global supply chain.

Over the 5-year investment, the Swiss pharma giant expects to add 200 jobs over next year and another 300 by the end of 2023.

Introduced as a $190 million global pharmaceutical development site in 2011, the campus currently houses Roche’s Canadian commercial unit as well as product development, global procurement and pharma informatics. The new expansion will see it organize manufacturing across 13 plants and 11 sites, according to FiercePharma.

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