Cara touts sub­group in failed atopic der­mati­tis tri­al, but stock craters

Cara Ther­a­peu­tics will join the grow­ing list of biotech to launch a Phase III de­spite fail­ing Phase II.

The itch-fo­cused com­pa­ny an­nounced Thurs­day that its cen­tral drug, a pill called Ko­r­su­va, failed to sig­nif­i­cant­ly al­le­vi­ate itch­ing in pa­tients with atopic der­mati­tis when com­pared with place­bo. The drug missed both the pri­ma­ry end­point, the change in av­er­age score on a stan­dard itch scale af­ter 12 weeks, and the key sec­ondary end­point: The pro­por­tion of pa­tients who im­proved by at least 4 points.

On the pri­ma­ry end­point, the study neared sta­tis­ti­cal sig­nif­i­cance, with a p-val­ue of 0.073 for the high dose and 0.111 for all dose. But it did not for the sec­ondary end­point, with p-val­ue of 0.55 and 0.59 for the mid and high dos­es.

The tri­al is one of sev­er­al Cara is run­ning for the drug across a va­ri­ety of dis­eases. The FDA is now eval­u­at­ing un­der pri­or­i­ty re­view an in­jectable form of Ko­r­su­va for dial­y­sis, a po­ten­tial­ly lu­cra­tive in­di­ca­tion that Vi­for spent $150 mil­lion up­front to com­mer­cial­ize in the US. Atopic der­mati­tis is one of two oth­er mid-stage ef­forts Cara is run­ning for Ko­r­su­va af­ter their pain pro­gram tanked, de­spite their best ef­forts to spin the da­ta.

Al­though they missed the two key end­points, Cara is ar­gu­ing that their re­sults in a sub-group of­fer a path to a piv­otal tri­al and even­tu­al ap­proval. In what the com­pa­ny refers to in their press re­lease as an­oth­er “Pri­ma­ry End­point,” the drug sig­nif­i­cant­ly im­proved symp­toms in a sub­group of pa­tients who had a more mild form of atopic der­mati­tis. This group, rep­re­sent­ing 257 pa­tients, or 64% of the 401-per­son study, saw sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ments in itch­ing symp­toms af­ter 12 weeks, with a p-val­ue of 0.036.

Joana Goncalves

Pa­tients in the milder group were al­so more like­ly to see an im­prove­ment by at least 4 points, with a p-val­ue of 0.03. In that group, 32% of pa­tients in the treat­ment group saw a 4-point im­prove­ment com­pared to 19% of place­bo pa­tients.

“We view this as a pos­i­tive out­come,” Cara CMO Joana Goncalves said on a con­fer­ence call “What we learned in the study is that [Ko­r­su­va] is most ef­fec­tive in the mild to mod­er­ate pa­tient pop­u­la­tion.”

Cara now plans to move for­ward with a Phase III for just the mild to mod­er­ate pa­tient pop­u­la­tion. In­vestors, how­ev­er, ap­peared un­con­vinced by the drug’s prospects, with the stock $CARA drop­ping 40%, from $25.67 t0 $15.67.

On Cara’s con­fer­ence call, an­a­lysts raised ques­tions about whether the ef­fect size they saw in the sub­group would be mean­ing­ful for pa­tients and whether they’d be able to charge as much as they would have for more se­vere pa­tients. They al­so point­ed out that, on one end­point, pa­tients who re­ceived a low dose per­formed bet­ter than pa­tients on the high dose — the op­po­site of what drug de­vel­op­ers gen­er­al­ly look for.

Derek Chalmers

“Does that make sense to you?” Stifel’s Annabel Samimy asked.

CEO Derek Chalmers said it was just an anom­aly. The in­di­vid­ual dose groups were sim­ply not large enough.

“We think that’s sim­ply a pow­er­ing is­sue,” said Chalmers.

The com­pa­ny al­so ar­gued that mild to mod­er­ate pa­tients still present a sig­nif­i­cant op­por­tu­ni­ty, as they can’t take in­jectable drugs like JAK in­hibitors and they aren’t suf­fi­cient­ly cov­ered by over-the-counter op­tions.

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

Roger Perl­mut­ter lines up deals, fresh fund­ing at Eikon; Sec­ond RSV vac­cine ap­proved; Sev­er­al biotechs flash­ing red; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As you come back to our website this weekend for ASCO news, don’t forget to check out our updated event lineup at BIO, which will cover everything from the current state of VC investing in biotech to top pharma R&D chiefs discussing how to make pipeline decisions.

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Full TIG­IT da­ta from Gilead, Ar­cus show low­er PFS rates than De­cem­ber read­out: #AS­CO23

CHICAGO — Gilead and Arcus unveiled a fuller snapshot of a Phase II study testing their experimental cancer immunotherapy combo that showed lower progression-free survival rates than its previous update, results that are likely to spark further debate over the closely-watched clinical trial.

Last December, the anti-TIGIT/anti-PD-L1 combo, positioned as a first-line treatment for non-small cell lung cancer, recorded data that drew mixed reactions. The latest analysis, presented Saturday afternoon at ASCO, included only a handful more patients than the previous update, but PFS rates fell — in one cohort by nearly three months.

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Bris­tol My­er­s' Op­di­vo keeps can­cer at bay in more lym­phoma pa­tients than Seagen's Ad­cetris in PhI­II: #AS­CO23

CHICAGO — In a study pitting Seagen’s Adcetris against Bristol Myers Squibb’s Opdivo in newly diagnosed patients with advanced classic Hodgkin lymphoma, a greater proportion of those who received Opdivo saw no cancer growth at one year compared to those who got Adcetris.

In addition, patients in the Opdivo arm of the Phase III trial reported reduced toxicities, according to lead investigator Alex Herrera, a hematologist-oncologist at City of Hope’s cancer cancer in Duarte, CA. Notably, the trial included more than 200 children across both arms. Generally, more than half of children with advanced Hodgkin lymphoma receive radiation therapy, but in this trial, dubbed SWOG S1826, only a handful of patients in the two arms received radiotherapy, sparing many children from long-term side effects of radiation.

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Servi­er’s vo­rasi­denib stalls pro­gres­sion of brain can­cer by 61% in piv­otal PhI­II IN­DI­GO study: #AS­CO23

An experimental pill from Servier Pharmaceuticals showed potentially practice-changing results in a narrow group of brain cancer patients, cutting the risk of their cancers progressing by 61%, according to a late-stage clinical trial.

The drug, vorasidenib, is a precision medicine that only works in certain people whose cancer carries mutations in one of two genes called IDH1/2. Doctors hope that the therapy will delay the need for chemotherapy or radiation, which are often used to combat relapses in patients who’ve previously undergone surgery to remove brain tumors.

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As­traZeneca tri­al shows mod­est ben­e­fit in ovar­i­an can­cer, but doc­tors say it's hard to ap­ply find­ings: #AS­CO23

CHICAGO — Adding AstraZeneca’s Imfinzi and Lynparza to the treatment regimen for patients with advanced ovarian cancer and no BRCA mutation extended progression-free survival (PFS) by five months, according to interim data released at the ASCO annual meeting Saturday morning.

However, the design of the Phase III study obscures how much Imfinzi is contributing to the PFS extension, doctors said, making it difficult to apply the findings to clinical practice.

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Keytru­da be­fore and af­ter lung can­cer surgery cuts re­lapse risk by 42%, but doesn’t im­prove sur­vival: #AS­CO23

CHICAGO — Merck has found partial success with its latest effort to more aggressively treat earlier stages of lung cancer.

On Saturday the pharma giant announced results from a large trial in which patients received Merck’s immunotherapy Keytruda plus chemotherapy before surgeons removed their tumors, followed by another course of Keytruda afterward.

The Phase III study, called KEYNOTE-671, enrolled 800 people with the early stages of the most common kind of lung cancer: non-small cell lung cancer, or NSCLC. Everyone got chemo before surgery, and half also got Keytruda before and after. At two years, 62.4% of those who got Keytruda kept their cancer at bay, compared to 40.6% who got a placebo.

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Grail’s blood test charts path for di­ag­nos­ing pa­tients sus­pect­ed of hav­ing can­cer in large study: #AS­CO23

Grail’s vision is simple but bold. The blood testing company has long held that people are often diagnosed with cancer too late. If seemingly healthy people were screened for early signs of the disease before symptoms appear, they may be able to get more effective treatments that nip cancer in the bud.

That premise is the basis of Grail’s commercial blood test, Galleri, which searches for the genetic fingerprints of cancer in the blood. The test, launched in 2021, reaped $55 million in sales last year, but now the company is setting its sights on a new market: patients suspected of having cancer due to symptoms such as abdominal pain, rectal bleeding or unexplained weight loss. Rather than administering expensive scans or conducting invasive biopsies right away, Grail hopes doctors will consider a simple blood test.

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Take­da ax­es gene ther­a­py deal with Po­sei­da Ther­a­peu­tics amid broad­er re­think

Less than two years after Takeda inked a collaboration with Poseida Therapeutics to develop six liver-directed and hematopoietic stem cell-directed in vivo gene therapies, Takeda will end the partnership on July 30, the company confirmed to Endpoints News.

The breakup is not unexpected, coming on the heels of Takeda’s April announcement that it planned to stop discovery and preclinical work in AAV gene therapy, as well as research and preclinical work on rare hematology. A representative for Takeda confirmed that the partnership ended because of the company’s decision to stop that work.

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