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.”

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive”  pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Ex­elix­is pulls a sur­prise win in thy­roid can­cer just days ahead of fi­nal Cabome­tyx read­out

Exelixis added a thyroid cancer indication to its super-seller Cabometyx’s label on Friday — months before the FDA was expected to make a decision, and days before the company was set to unveil the final data at #ESMO21.

At a median follow-up of 10.1 months, differentiated thyroid cancer patients treated with Cabometyx (cabozantinib) lived a median of 11 months without their disease worsening, compared to just 1.9 months for patients given a placebo, Exelixis said on Monday.

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Ex-My­lan em­ploy­ee pleads guilty to in­sid­er trad­ing, il­le­gal­ly deal­ing on FDA ap­provals, earn­ings and Up­john merg­er

A former Mylan IT executive pleaded guilty Friday to an insider trading scheme where he bought and sold stock options on another executive’s advice.

Prosecutors secured the plea from Dayakar Mallu, Mylan’s former VP of global operations information technology, after uncovering the plan. Mallu collaborated with an unnamed “senior manager,” the SEC said, to trade options ahead of Mylan public announcements regarding FDA approvals, revenue reports and its merger with the Pfizer generics subsidiary Upjohn. The two subsequently shared profits.

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As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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