#AS­CO21: No­var­tis gears up for CAR-T fight with Gilead in fol­lic­u­lar lym­phoma — and safe­ty could de­fine the bat­tle

Since win­ning the first CAR-T ap­proval in the US back in 2017, No­var­tis has been hard at work ex­pand­ing the reach of its block­buster can­cer drug Kym­ri­ah. Gilead’s Yescar­ta beat it to the punch in fol­lic­u­lar lym­phoma (FL) back in March — but now, No­var­tis says it has new piv­otal da­ta that could give its old ri­val a run for its mon­ey.

Of 94 pa­tients giv­en Kym­ri­ah for re­lapsed or re­frac­to­ry FL, 86% re­spond­ed, ac­cord­ing to pri­ma­ry re­sults re­leased ahead of AS­CO 2021. A to­tal of 66% saw a com­plete re­sponse — which is just a bit high­er than the 65% No­var­tis tout­ed up­on shar­ing in­ter­im re­sults from the Phase II ELARA tri­al back in De­cem­ber.

These new ef­fi­ca­cy re­sults in­clude near­ly twice as many pa­tients as the in­ter­im analy­sis, No­var­tis said. The over­all re­sponse rate al­so saw a small bump, up from the 83% rate record­ed in De­cem­ber. Me­di­an du­ra­tion of re­sponse, pro­gres­sion free sur­vival, and over­all sur­vival were not yet reached, ac­cord­ing to No­var­tis.

De­spite some fa­mil­iar ef­fi­ca­cy fig­ures, Kym­ri­ah could set it­self apart on the safe­ty front. No pa­tients ex­pe­ri­enced Grade 3 or 4 cy­tokine re­lease syn­drome, a well-doc­u­ment­ed side ef­fect of CAR-T ther­a­py. Those re­sults top Yescar­ta’s ZU­MA-5 da­ta, which showed Grade 3 or high­er CRS in 8% of pa­tients.

Grade 1 or 2 CRS oc­curred in 49% of pa­tients in ELARA, with 9% of pa­tients ex­pe­ri­enc­ing Grade 1 or 2 neu­ro­log­i­cal events. One pa­tient ex­pe­ri­enced Grade 4 neu­ro­log­i­cal events, but re­cov­ered. Three par­tic­i­pants died from pro­gres­sive dis­ease, though none of the deaths were treat­ment-re­lat­ed, ac­cord­ing to the Swiss phar­ma.

Ste­fan Hen­driks

No­var­tis plans on run­ning the new da­ta to reg­u­la­tors “as quick­ly as pos­si­ble,” ac­cord­ing to Ste­fan Hen­driks, the glob­al head of No­var­tis On­col­o­gy’s cell and gene di­vi­sion. He con­firmed in an email to End­points News that a sub­mis­sion for the new in­di­ca­tion will come some­time this year.

FL is the sec­ond most com­mon form of non-Hodgkin lym­phoma, with a five-year sur­vival rate of on­ly 20% for pa­tients in the third line and lat­er. Pa­tients with FL have ma­lig­nant tu­mors that grow slow­ly and can be­come more ag­gres­sive over time, and ef­fi­ca­cy of avail­able treat­ments drops off rapid­ly in lat­er lines. Pa­tients in ELARA had a me­di­an of four pri­or treat­ments, though some had tak­en as many as 13.

Yescar­ta won ap­proval as a third-line ther­a­py back in March, be­com­ing the first CAR-T ap­proved for re­lapsed/re­frac­to­ry FL. The OK was based on re­sults from the ZU­MA-5 tri­al, in which 91% of pa­tients saw a re­sponse, 60% of whom achieved a com­plete re­mis­sion, ac­cord­ing to Gilead. Me­di­an du­ra­tion of re­sponse had not been reached.

“As you know, di­rect cross tri­al com­par­isons are me­thod­i­cal­ly and sta­tis­ti­cal­ly not ap­pro­pri­ate due to dif­fer­ences in pa­tient char­ac­ter­is­tics, ef­fi­ca­cy out­come mea­sures (tim­ing) and in-pa­tient vs. out-pa­tient set­ting,” Hen­driks said in an email. “Head-to-head stud­ies have not been per­formed, and no com­par­i­son of safe­ty and ef­fi­ca­cy can be made.”

While Kym­ri­ah beat Yescar­ta out the gate back in 2017, Yescar­ta has the up­per hand in sales, at least in Q1 of this year. The Gilead drug pulled in $160 mil­lion last quar­ter, while Kym­ri­ah made No­var­tis $151 mil­lion.

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; and more

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Ab­b­Vie tacks on a new warn­ing to Rin­voq la­bel as safe­ty frets crimp JAK class

The safety problems that continue to plague the JAK class as new data highlight some severe side effects are casting a large shadow over AbbVie’s Rinvoq.

As a result of a recent readout highlighting major adverse cardiac events (MACE), malignancy, mortality and thrombosis with Xeljanz a couple of months ago, AbbVie put out a notice late Friday afternoon that it is adding the new class risks to its label for their rival drug.

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Biospec­i­men M&A: Dis­cov­ery ac­quires Al­bert Li's he­pa­to­cyte project; PhI­II tri­al on Bay­er's Nube­qa reached pri­ma­ry end­point

Discovery Life Sciences has acquired what claims to be the Maryland-based host of the world’s largest hepatocyte inventory, known as IVAL, to help researchers select more effective and safer drug candidates in the future.

The combined companies will now serve a wider range of drug research and development scientists, according to Albert Li, who founded IVAL in 2004 and is set to join the Discovery leadership team as the CSO of pharmacology and toxicology.

Re­searchers move clos­er to de­ci­pher­ing blood clots from As­traZeneca, J&J's Covid-19 vac­cines

Researchers may be nearing an answer for the mysterious and life-threatening blood clots that appeared on very rare occasions in people who received the J&J or AstraZeneca Covid-19 vaccine.

The new work builds on an early hypothesis researchers in Norway put forward last spring, when the cases first cropped up. They proposed the events were similar to blood clots that can occur in a small subset of patients who receive heparin, one of the most commonly used blood thinners.

Ed Kaye, Stoke Therapeutics CEO

Stoke touts ear­ly signs of ef­fi­ca­cy for Dravet syn­drome drug

Two and a half years after driving his antisense oligonucleotide platform to Wall Street, Stoke Therapeutics CEO Ed Kaye is painting a fuller picture of the company’s first clinical data. And though the trial wasn’t powered to detect statistical significance, Kaye says the readout shows early signs of efficacy in kids with a rare, drug-resistant form of epilepsy

STK-001 was well-tolerated in single and multiple doses in 22 Dravet syndrome patients between the ages of 2 and 18 years old, Stoke announced on Friday. What’s more, 12 of the 17 evaluable patients at the time (70.6%) saw reductions from baseline in convulsive seizure frequency, according to the company.