Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a nov­el com­peti­tor to Sanofi and Re­gen­eron’s Dupix­ent in se­vere asth­ma, Am­gen and As­traZeneca post­ed “ex­cit­ing” re­sults from their next-gen an­ti­body late last year. Now, the part­ners are show­ing their hands, and the re­sults look good enough for ap­proval.

Am­gen and As­traZeneca’s teze­pelum­ab plus stan­dard of care cut the rate of se­vere asth­ma at­tacks by 56% at the one-year mark com­pared with SOC alone, ac­cord­ing to full da­ta from the Phase III NAV­I­GA­TOR study pre­sent­ed Fri­day at the vir­tu­al Amer­i­can Acad­e­my of Al­ler­gy, Asth­ma & Im­munol­o­gy meet­ing. And those sig­nif­i­cant re­sults were con­sis­tent re­gard­less of pa­tients’ base­line eosinophil counts.

The full re­sults tee up teze­pelum­ab, a once-month­ly in­fu­sion that al­ready sports the FDA’s break­through ther­a­py des­ig­na­tion, for a quick fil­ing from the Big Phar­ma part­ners. The pair re­leased topline re­sults from the NAV­I­GA­TOR study back in No­vem­ber, call­ing the da­ta “ex­cit­ing” and “ground­break­ing.”

In a re­lease, Am­gen said the NAV­I­GA­TOR re­sults make teze­pelum­ab the first bi­o­log­ic to sig­nif­i­cant­ly low­er the rate of an­nu­al­ized asth­ma ex­ac­er­ba­tions over stan­dard of care re­gard­less of base­line eosinophils, spe­cial­ized white blood cells that cause in­flam­ma­tion. The low­er eosinophil counts are of par­tic­u­lar in­ter­est for an­a­lysts, who have not­ed that oth­er se­vere asth­ma meds, in­clud­ing Dupix­ent, aren’t ap­proved for those pa­tients.

The drug al­so spurred sig­nif­i­cant re­duc­tions re­gard­less of pa­tients’ al­ler­gy sta­tus and frac­tion­al ex­haled ni­tric ox­ide (FeNO) lev­el, both com­mon bio­mark­ers in de­ter­min­ing treat­ment op­tions.

Teze­pelum­ab is de­signed to block TSLP, an ep­ithe­lial cy­tokine that sits up­stream of in­flam­ma­to­ry cy­tokines such as IL-4, IL-5 and IL-13. By tar­get­ing mul­ti­ple path­ways re­spon­si­ble for asth­ma, re­searchers be­lieve that they could help those whose symp­toms are not al­le­vi­at­ed by cur­rent ther­a­pies.

How­ev­er, teze­pelum­ab has flopped on at least one key dif­fer­en­tia­tor from drugs like Dupix­ent. In Phase III da­ta pre­sent­ed in De­cem­ber, teze­pelum­ab failed to low­er the num­ber of back­ground oral cor­ti­cos­teroids pa­tients were re­quired to take to man­age their symp­toms. Am­gen called the re­sults “sur­pris­ing” and tried to tag tri­al de­sign flaws as a pos­si­ble cul­prit. Full da­ta from that study have yet to be re­leased.

Ei­ther way, there’s a prob­lem: Dupix­ent did cut the num­ber of back­ground cor­ti­cos­teroids in its own piv­otal tri­als in se­vere asth­ma, and an­a­lysts wor­ry physi­cians pri­mar­i­ly care about get­ting their pa­tients off as many steroids as pos­si­ble.

Even still — and this is a sig­nif­i­cant un­der­score to the mar­ket po­ten­tial here — some an­a­lysts have placed teze­pelum­ab’s po­ten­tial peak sales at $2.5 bil­lion. But that’s the cost of hop­ing to do busi­ness in the same mar­ket as Dupix­ent, the leader in the atopic der­mati­tis club­house and the linch­pin of Sanofi and Re­gen­eron’s near-term growth plans.

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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Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Herceptin has long stood as standard of care across multiple advanced cancers, but a suite of next-gen players are looking to beat the aging giant at its own game. In HER2-expressing esophageal cancer, BeiGene partner Zymeworks thinks its bispecific antibody could have the juice to get it done.

Zymeworks’ bispecific antibody zanidatamab, combined with one of two chemotherapy regimens, posted an overall response rate of 75% in patients with advanced gastroesophageal adenocarcinoma (GEA) who had not previously received a HER2-targeted cancer therapy, the Vancouver-based biotech said Thursday.

UP­DAT­ED: Gilead keeps push­ing trove of Trodelvy da­ta as it seeks to be­come new stan­dard of care in TNBC

Gilead is continuing to churn out results for its newly approved drug Trodelvy, and #ESMO21 is the latest stop on the data train.

The biopharma put out new quality of life data in second-line patients with metastatic triple-negative breast cancer, saying that a sub-analysis from their Phase III study showed significant and clinically meaningful improvements in health-related quality of life over standard of care.