In next-gen BTK bat­tle, Ab­b­Vie and J&J tout piv­otal da­ta back­ing Im­bru­vi­ca as a com­bo treat­ment

Last week, As­traZeneca took a swing at J&J and Ab­b­Vie’s first-gen­er­a­tion BTK in­hibitor Im­bru­vi­ca in the blood can­cer chron­ic lym­pho­cyt­ic leukemia with long-term da­ta from a head-to-head tri­al. But the part­ners aren’t go­ing down with­out a fight.

Ab­b­Vie and Janssen un­veiled piv­otal da­ta on Sat­ur­day show­ing that first-line CLL pa­tients who re­ceived Im­bru­vi­ca and Ab­b­Vie’s Roche-part­nered Ven­clex­ta lived longer with­out dis­ease pro­gres­sion than pa­tients on Gazy­va and the chemother­a­py chlo­ram­bu­cil. The Phase III GLOW tri­al en­rolled 211 el­der­ly pa­tients, or those with co­mor­bidi­ties or con­cur­rent ill­ness­es. Over­all, the me­di­an age was 71 years old.

Me­di­an pro­gres­sion-free sur­vival wasn’t reached in the Im­bru­vi­ca arm com­pared with 21 months in the Gazy­va arm — show­ing a 78% re­duc­tion in the risk of dis­ease pro­gres­sion or death, the part­ners said.

At three months post-treat­ment, un­de­tectable min­i­mal resid­ual dis­ease was 51.9% in the bone mar­row of Im­bru­vi­ca pa­tients com­pared to 17.1% in the Gazy­va arm (p<0.0001), and 54.7% ver­sus 39% in the pe­riph­er­al blood (p<0.0001). Un­de­tectable min­i­mal resid­ual dis­ease in the pe­riph­er­al blood was sus­tained by 85% of pa­tients one year post-treat­ment in the Im­bru­vi­ca arm, ac­cord­ing to the da­ta.

At the time of as­sess­ment, 38.7% of Im­bru­vi­ca pa­tients saw com­plete re­spons­es (in­clud­ing those with in­com­plete hema­to­log­ic re­cov­ery), ver­sus 11.4% of pa­tients on Gazy­va and chlo­ram­bu­cil (p<0.0001).

“The da­ta from GLOW showed that ibru­ti­nib in an oral, once-dai­ly fixed-du­ra­tion com­bi­na­tion with vene­to­clax out­per­formed a stan­dard chemoim­munother­a­py reg­i­men for old­er or un­fit pa­tients, pro­vid­ing the first com­par­a­tive ev­i­dence that this ap­proach has the po­ten­tial to im­prove depth of re­sponse and, there­fore, ex­tends time to pro­gres­sion ver­sus stan­dard ther­a­py,” the study’s prin­ci­pal in­ves­ti­ga­tor Arnon Kater said in a state­ment.

Im­bru­vi­ca in­hibits BTK, an en­zyme that plays a cru­cial role in onco­genic sig­nal­ing that’s key for the pro­lif­er­a­tion and sur­vival of leukemic cells in many B-cell ma­lig­nan­cies. The block­buster drug was first ap­proved in 2013, but safe­ty and tol­er­a­bil­i­ty is­sues soon emerged. Since then, sec­ond-gen­er­a­tion can­di­dates like As­traZeneca’s Calquence have been po­si­tioned as safer but equal­ly ef­fec­tive al­ter­na­tives.

At #AS­CO21, As­traZeneca un­veiled long-term da­ta that showed Calquence matched Im­bru­vi­ca for a me­di­an PFS of 40.9 months in CLL pa­tients, but best­ed Im­bru­vi­ca when it came to oc­cur­rence of car­diac events. In­ci­dence of all-grade atri­al fib­ril­la­tion — an ir­reg­u­lar heart­beat that can lead to stroke or heart fail­ure — was 9.4% in the Calquence arm, com­pared to a 16% rate in the Im­bru­vi­ca arm (p=0.02).

Last week, BeiGene read out in­ter­im re­sults from a Phase III study com­par­ing its own BTK in­hibitor Brukin­sa to Im­bru­vi­ca in pa­tients with re­lapsed/re­frac­to­ry CLL or small lym­pho­cyt­ic lym­phoma (the same dis­ease as CLL but in the lymph nodes). An in­de­pen­dent re­view com­mit­tee re­port­ed that the over­all re­sponse in the Brukin­sa arm was nu­mer­i­cal­ly high­er but not sta­tis­ti­cal­ly sig­nif­i­cant. How­ev­er, there was a sta­tis­ti­cal­ly sig­nif­i­cant low­er risk of atri­al fib­ril­la­tion or flut­ter.

In the GLOW study, Ab­b­Vie and Janssen said the safe­ty pro­file of Im­bru­vi­ca and Ven­clex­ta was “con­sis­tent with CLL treat­ment in an old­er pop­u­la­tion with co­mor­bidi­ties.” Sev­en pa­tients died dur­ing treat­ment in the Im­bru­vi­ca arm, com­pared to two deaths in the Gazy­va arm.

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.

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.

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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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.

Jay Bradner (Jeff Rumans for Endpoints News)

Div­ing deep­er in­to in­her­it­ed reti­nal dis­or­ders, No­var­tis gob­bles up an­oth­er bite-sized op­to­ge­net­ics biotech

Right about a year ago, a Novartis team led by Jay Bradner and Cynthia Grosskreutz at NIBR swooped in to scoop up a Cambridge, MA-based opthalmology gene therapy company called Vedere. Their focus was on a rather narrow market niche: inherited retinal dystrophies that include a wide range of genetic retinal disorders marked by the loss of photoreceptor cells and progressive vision loss.

But that was just the first deal that whet their appetite.

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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.

Mi­rati's KRAS drug looks like the ear­ly fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed numerically higher response rates than sotorasib solo and as part of a combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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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.