Clo­vis' Rubra­ca wins prostate can­cer ap­proval, but da­ta from ri­val Lyn­parza damp­en com­mer­cial ex­pec­ta­tions

While As­traZeneca and Mer­ck’s mar­ket-lead­ing Lyn­parza seem­ing­ly pipped Clo­vis On­col­o­gy’s ri­val Rubra­ca in help­ing prostate can­cer pa­tients, Rubra­ca has, as ex­pect­ed, made it across the fin­ish line first.

On Fri­day, the FDA ap­proved Rubra­ca in pa­tients with BR­CA mu­ta­tion-as­so­ci­at­ed metasta­t­ic cas­tra­tion-re­sis­tant prostate can­cer (mCR­PC) who have been treat­ed pre­vi­ous­ly with an­dro­gen re­cep­tor-di­rect­ed ther­a­py as well as chemother­a­py. The ap­proval marks the first ever for a PARP in­hibitor in the prostate can­cer set­ting.

The ap­proval was based on a sin­gle-arm TRI­TON2 study, with a 44% con­firmed ob­jec­tive re­sponse rate in 62 sec­ond-line pa­tients. A late-stage study eval­u­at­ing the im­pact of Rubra­ca on over­all sur­vival in prostate can­cer pa­tients is on­go­ing.

“While Clo­vis has an on­go­ing ran­dom­ized tri­al with OS as a key sec­ondary end­point, TRI­TON3, we would not ex­pect this ben­e­fit to be demon­strat­ed in time to have a sig­nif­i­cant com­mer­cial im­pact, as Lyn­parza may have al­ready ad­vanced to the front­line, based on the Phase 3 PRO­pel tri­al with ini­tial da­ta ex­pect­ed in 2021,” SVB Leerink an­a­lyst An­drew Berens wrote in a note in late April.

In April, Lyn­parza eclipsed the an­ti-an­dro­gen ther­a­pies Pfiz­er and Astel­las’ Xtan­di and John­son & John­son’s Zyti­ga by help­ing men with metasta­t­ic, cas­tra­tion-re­sis­tant prostate can­cer with BR­CA or ATM gene mu­ta­tions live longer. Pre­vi­ous­ly un­veiled da­ta al­so showed the PARP in­hibitor su­per­seded the im­pact of the an­dro­gen ther­a­pies at re­duc­ing the risk of dis­ease pro­gres­sion or death — by a sharp 66%.

An­drew Berens

“While Rubra­ca re­quires pri­or treat­ment with both an an­dro­gen-re­cep­tor and tax­ane ther­a­py, Lyn­parza’s reg­is­tra­tional PRO­found study on­ly re­quires pri­or treat­ment with an an­dro­gen-re­cep­tor treat­ment…as such, while Rubra­ca is ap­proved as a 3L ther­a­py, Lyn­parza could ob­tain ap­proval as a 2L + agent,” Berens wrote in a note on Mon­day. “Fur­ther­more, AZN’s PRO­pel study, which would ex­pand the Lyn­parza la­bel in­to 1L mCR­PC treat­ment in com­bi­na­tion with abi­raterone, is ex­pect­ed to an­nounce da­ta in 2021, po­ten­tial­ly mov­ing Lyn­parza to the front­line. In com­par­i­son, CLVS’ TRI­TON3 study in­ves­ti­gat­ing Rubra­ca ver­sus physi­cian’s choice of an­dro­gen-re­cep­tor or chemother­a­py in 1L mCR­PC will not read out da­ta un­til 2022.”

Berens has ad­just­ed his peak Rubra­ca prostate rev­enue to $130 mil­lion glob­al­ly.

Akin to Lyn­parza, Clo­vis’ Rubra­ca and GSK’s Ze­ju­la are poly (ADP-ri­bose) poly­merase (PARP) in­hibitors. PARP is a pro­tein used by dam­aged cells to ini­ti­ate re­pair, and by thwart­ing it, the class of drugs is en­gi­neered to pre­vent can­cer cells from re­pair­ing them­selves, there­by cat­alyz­ing their de­struc­tion.

While drug de­vel­op­ers have pri­mar­i­ly re­lied on BR­CA mu­ta­tions to iden­ti­fy pa­tients who can ben­e­fit from this fam­i­ly of ther­a­pies, sci­en­tists have sug­gest­ed that de­fects in oth­er genes in­volved in DNA re­pair — which ren­der cells can­cer­ous — could be prime tar­gets too.

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.

Jacob Van Naarden (Eli Lilly)

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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So what hap­pened with No­var­tis' gene ther­a­py group? Here's your an­swer

Over the last couple of days it’s become clear that the gene therapy division at Novartis has quietly undergone a major reorganization. We learned on Monday that Dave Lennon, who had pursued a high-profile role as president of the unit with 1,500 people, had left the pharma giant to take over as CEO of a startup.

Like a lot of the majors, Novartis is an open highway for head hunters, or anyone looking to staff a startup. So that was news but not completely unexpected.

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Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

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.

When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

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.