Covid-19 af­flicts Eli Lil­ly’s share price and a KRAS drug gets tossed, but Jar­diance win salves the wound as an an­ti­body ef­fort ad­vances to PhII

Shares of Eli Lil­ly $LLY tum­bled close to 2% on Thurs­day in a tox­ic re­ac­tion to its mixed rev­enue per­for­mance in the face of the pan­dem­ic dur­ing Q2. But in­vestors found so­lace in a promis­ing Phase III read­out for Jar­diance, as their block­buster con­tin­ues to blaze a trail to much big­ger mar­kets.

Their SGLT2 in­hibitor beat out a place­bo in re­duc­ing the risk for the com­pos­ite of car­dio­vas­cu­lar death or hos­pi­tal­iza­tion due to heart fail­ure, when added to stan­dard of care. The drug hit the pri­ma­ry end­point, added Lil­ly, not­ing that the full da­ta read­out will come at the Eu­ro­pean So­ci­ety of Car­di­ol­o­gy (ESC) Con­gress at the end of Au­gust.

Swept out in the Q2 cleanup, though, was Lil­ly’s ear­ly stage KRAS G12C drug LY3499446. Af­ter Am­gen spurred hope for a big KRAS play, with a va­ri­ety of play­ers look­ing to make progress on a tar­get that has long been con­sid­ered un­drug­gable, added da­ta have dimmed hopes for broad ap­plic­a­bil­i­ty. And now Lil­ly, which has been steadi­ly re­work­ing its on­col­o­gy pipeline and brand un­der Loxo chief Josh Bilenker, wants out. The key is­sue was safe­ty.

Lil­ly’s state­ment to End­points News:

While we were ini­tial­ly ex­cit­ed to ex­plore the po­ten­tial of LY3499446, we saw un­ex­pect­ed tox­i­c­i­ty and de­cid­ed not to in­vest ad­di­tion­al time and re­sources in a pro­gram that may not be as clin­i­cal­ly and com­pet­i­tive­ly rel­e­vant as we hoped. We are tak­ing a very dis­ci­plined ap­proach to build­ing our pipeline and are sin­gu­lar­ly fo­cused on dis­cov­er­ing and de­vel­op­ing med­i­cines that we be­lieve will be tru­ly dif­fer­en­ti­at­ed and mat­ter to pa­tients.

The news on Jar­diance, one of their fastest grow­ing fran­chis­es at Lil­ly, will be sweet­er for in­vestors.

Vamil Di­van at Mizuho not­ed:

(I)t is clear to us that to­day’s news, com­bined with pos­i­tive news we have seen re­cent­ly from SGLT-2 in­hibitors in pa­tients with kid­ney dis­ease, is go­ing to open up large new mar­kets for the SGLT-2 class, with Jar­diance the clear mar­ket leader.

Oth­er drugs in the class, in­clud­ing Farx­i­ga from As­traZeneca, have been mak­ing their own ad­vances on the car­dio side of the med­ical equa­tion.

“The re­sults of the EM­PER­OR-Re­duced tri­al in­di­cate that SGLT2 in­hibitors have the po­ten­tial to be­come a new stan­dard of care for this dis­ease, which will be a mean­ing­ful ad­di­tion to cur­rent­ly es­tab­lished treat­ments,” not­ed Mil­ton Pack­er, chair of the ex­ec­u­tive com­mit­tee for the de­vel­op­ment pro­gram.

An­a­lysts have al­so been close­ly fol­low­ing Lil­ly’s an­ti­body de­vel­op­ment pro­gram for CoV555, part­nered with Ab­Cellera. In their Q2 state­ment, the com­pa­ny said they had com­plet­ed dos­ing in the first study and launched a Phase II tri­al, with da­ta ex­pect­ed in the fourth quar­ter.

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

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.

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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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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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Lisa Deschamps, AviadoBio CEO

Ex-No­var­tis busi­ness head hops over to a gene ther­a­py start­up — and she's reeled in $80M for a dash to the clin­ic

Neurologist and King’s College London professor Christopher Shaw has been researching neurodegenerative diseases like ALS and collaborating with drugmakers for the last 25 years in the hopes of pushing new therapies forward. But unfortunately, none of those efforts have come anywhere close to fruition.

“So, you know, after 20 years in the game, I said, ‘Let’s try and do it ourselves,’” he told Endpoints News. 

Vas Narasimhan, Novartis CEO (Thibault Camus/Pool via AP Images)

With gener­ic com­pe­ti­tion heat­ing up, Vas Narasimhan out­lines No­var­tis' growth plans at R&D day

Thursday marks Novartis’ annual R&D day, and with it comes CEO Vas Narasimhan’s attempt to spotlight the company’s pipeline strategy and emerging stars.

The biggest question entering Thursday’s presentation dealt with how the big biopharma will make up revenues from upcoming generic competition — Novartis says within the next five years, generics will eat away roughly $9 billion in sales. To offset this, Narasimhan outlined a strategy for 4% growth or higher until 2026, focusing on six key medicines he believes will see multibillion dollar profits during this time.

In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Reshma Kewalramani, Vertex CEO (Vertex via YouTube)

Bat­tling a line­up of skep­tics, Ver­tex claims an­oth­er ear­ly clin­i­cal win — this time in kid­ney dis­ease

Vertex claimed its second early-stage win of the fall Wednesday, announcing positive results in a small study on a genetically defined form of kidney disease.

The 16-patient, Phase II trial focused on patients with focal segmental glomerulosclerosis, a rare disease where kidneys are unable to filter blood properly. Over 13 weeks on an experimental pill, the level of protein in the patients’ urine fell by an average of 47.6%.

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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