CEO Todd Zavodnick (Dermavant)

With new PhI­II da­ta in hand, Der­ma­vant lines up top­i­cal pso­ri­a­sis con­tender for a sprint to the fin­ish line

In the next cou­ple months, Der­ma­vant CEO Todd Za­vod­nick says he’ll sprint to the FDA with tap­inarof, the com­pa­ny’s “cos­met­i­cal­ly el­e­gant” van­ish­ing cream to treat pso­ri­a­sis. But be­fore that, he has more Phase III da­ta to share.

Around 20% of mod­er­ate to se­vere plaque pso­ri­a­sis pa­tients giv­en tap­inarof in two Phase III tri­als achieved 90% dis­ease clear­ance, mea­sured by the Pso­ri­a­sis Area and Sever­i­ty In­dex (PASI 90) at Week 12, Za­vod­nick shared Fri­day at the Amer­i­can Acad­e­my of Der­ma­tol­ogy vir­tu­al meet­ing. And around 67% and 60% of pa­tients in the tri­als felt itch re­lief start­ing as ear­ly as Week 2.

“We don’t talk PASI 90s with top­i­cals,” Za­vod­nick told End­points News. “We talk PASI 90s with an oral or an in­jectable.”

The new da­ta come from two Phase III tri­als dubbed PSOAR­ING 1 and 2, which en­rolled 510 and 515 adults with mild to se­vere plaque pso­ri­a­sis, re­spec­tive­ly.

Ac­cord­ing to Der­ma­vant, 18.8% of pa­tients giv­en tap­inarof achieved a 90% or greater re­duc­tion in PASI 90 at Week 12 com­pared to just 1.6% of pa­tients giv­en place­bo in PSOAR­ING 1, with a p-val­ue of 0.0005. In PSOAR­ING 2, 20.9% of pa­tients on tap­inarof achieved PASI 90, ver­sus 2.5% in the place­bo arm, with a p-val­ue less than 0.0001.

Itch re­duc­tion was mea­sured on the Peak Pru­ri­tis Nu­mer­i­cal Rat­ing Scale (PP-NRS). And ac­cord­ing to pa­tient-re­port­ed out­comes, 67.5% of those who re­ceived tap­inarof achieved a 4-point or high­er im­prove­ment on the scale from Week 2 through Week 12, com­pared to just 46.1% of pa­tients on place­bo in PSOAR­ING 1 (p=0.0004). In PSOAR­ING 2, 59.7% of pa­tients in the treat­ment arm saw a 4-point of high­er im­prove­ment, com­pared to 31.3% of those in the place­bo arm (p<0.0001.)

Za­vod­nick has a dis­tinct com­mer­cial plan in mind for tap­inarof, which Vivek Ra­maswamy’s team plucked from GSK back in 2018 for $330 mil­lion — $200 mil­lion up­front. The plaque pso­ri­a­sis mar­ket is high­ly com­pet­i­tive, abound­ing with drugs from big play­ers like Ste­lara, Skyrizi and Cosen­tyx.

Za­vod­nick sees the can­di­date as a re­place­ment for steroids in the top­i­cal space, while leav­ing the most se­vere cas­es to the ul­tra-ef­fec­tive bi­o­log­ics, where he says the cream could act as an add-on ther­a­py.

“I think pa­tients that have mild to mod­er­ate pso­ri­a­sis are go­ing to look to tap­inarof first-line,” he said. “If a pa­tient needs more than a top­i­cal be­cause of their body sur­face area af­fect­ed, I think you’re look­ing at an oral/in­jectable op­por­tu­ni­ty, and 75% of those pa­tients are al­ways get­ting a top­i­cal with that,” adding that the beau­ty of non­s­teroidals is there’s no lim­it to their use.

Der­ma­vant an­nounced tap­inarof met its pri­ma­ry end­points in PSOAR­ING 1 and 2 back in Au­gust — clear or near­ly clear cas­es of pso­ri­a­sis com­pared to a place­bo, with a min­i­mum 2-grade im­prove­ment on Physi­cian Glob­al As­sess­ment, a com­mon­ly used score sheet. Tap­inarof al­so cleared a key sec­ondary end­point, PASI 75, at Week 12. In both PSOAR­ING 1 and 2, tap­inarof reg­is­tered a 35.4% and 40.2% score on the pri­ma­ry, com­pared to mar­gin­al gains for the place­bo, and a 36.1% and 47.6% score on PASI 75.

In Feb­ru­ary, Der­ma­vant read out long-term da­ta from the PSOAR­ING 3 tri­al, which showed im­prove­ments be­yond Week 12. No new safe­ty sig­nals were seen over the 52 weeks, and 57.3% of pa­tients who en­tered the study with a PGA score of 2 or high­er end­ed up with a score of 0 or 1, the com­pa­ny an­nounced.

Pa­tients’ symp­toms didn’t flare back up for a me­di­an of four months, Za­vod­nick added.

The new da­ta on itch re­lief set tap­inarof up for a Phase III tri­al launch this year, Za­vod­nick said. Back in Feb­ru­ary, the CEO said tap­inarof could be the foun­da­tion on which Der­ma­vant builds a “multi­bil­lion-dol­lar or­ga­ni­za­tion.” Af­ter all, the com­pa­ny wouldn’t be a “Vant” if it didn’t promise big things at a fast pace.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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Mi­rati's KRAS drug looks like the 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 response rates grater than sotorasib solo  and as part of 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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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; 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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

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.

Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.