Bill Lundberg, Merus CEO

#AS­CO21: Eli Lil­ly-part­nered Merus re­veals new da­ta for NRG1 fu­sion can­cers in­clud­ing pan­cre­at­ic and NSCLC

One of Eli Lil­ly’s newest R&D part­ners re­vealed some new da­ta at #AS­CO21 for an in-house pro­gram, and it’s one that could cov­er a broad range of sol­id tu­mors with rare ge­net­ic mu­ta­tions.

The Dutch biotech Merus NV re­port­ed that their ex­per­i­men­tal drug zeno­cu­tuzum­ab, re­ferred to as “zeno,” in­duced par­tial re­spons­es in 13 of 45 pa­tients with NRG1 fu­sion-pos­i­tive can­cers as of April 13 cut­off date, good for an over­all re­sponse rate of 29%. Merus is eval­u­at­ing the can­di­date in a sin­gle-arm Phase I/II study with 61 en­rolled pa­tients.

No­tably, 12 of the evalu­able pa­tients came in­to the tri­al with NRG1 pos­i­tive pan­cre­at­ic can­cer, with five see­ing con­firmed par­tial re­spons­es.

Merus al­so looked at pa­tients with NRG1 pos­i­tive non-small cell lung can­cer, ob­serv­ing that six of 24 such pa­tients achieved par­tial re­spons­es by the cut­off. The biotech not­ed that a sev­enth pa­tient here reached par­tial re­sponse af­ter the cut­off date as well.

Nine oth­er pa­tients with oth­er undis­closed NRG1 pos­i­tive can­cers reached the evalu­able stage by April 13, with two hit­ting a par­tial re­sponse. The full tri­al pop­u­la­tion en­rolled with a me­di­an of two pri­or lines of ther­a­py, and re­search has sug­gest­ed the mu­ta­tion is typ­i­cal­ly as­so­ci­at­ed with a poor­er prog­no­sis rel­a­tive to oth­er can­cer pa­tients.

CEO Bill Lund­berg told End­points News that the num­ber of can­cer pa­tients whose tu­mors have such mu­ta­tions is rel­a­tive­ly small. In pan­cre­at­ic can­cer, NRG1 fu­sion-pos­i­tive mu­ta­tions make up about 0.5% to 1.5% of tu­mors, while in NSCLC they ac­count for any­where be­tween 0.3% and 3%.

Even though lung and pan­cre­at­ic can­cers are vast­ly dif­fer­ent, Lund­berg said the NRG1 mu­ta­tion can oc­cur in the ep­ithe­lial cells lin­ing both or­gans.

“It’s turned out over the years that the dri­vers of can­cer can be sim­i­lar re­gard­less of whether it’s in an ep­ithe­lial cell in the pan­creas or an ep­ithe­lial cell in the lung,” Lund­berg said. “And there have been a num­ber of these can­cer dri­ver mu­ta­tions, whether it’s a RAF dri­ver, for which a drug just got ap­proved a week ago, or it’s these NTRK fu­sions, or RET or ROS mu­ta­tions.”

NRG1 mu­ta­tions oc­cur when one part of the chro­mo­some is “lopped” on­to an­oth­er part of the DNA, Lund­berg added. It’s a nor­mal lig­and for the HER3 pro­tein and binds to it, al­low­ing the pro­tein to fur­ther bind to HER2. Zeno, then, func­tions by bind­ing to both HER2 and HER3, pre­vent­ing HER3 from spurring the mu­ta­tion and specif­i­cal­ly block­ing the lig­and.

Lund­berg is keep­ing his cards close to the vest re­gard­ing when Merus would be ready to sub­mit an ap­pli­ca­tion to the FDA. He wouldn’t put a time­line on when the Phase I/II might be com­plet­ed, on­ly say­ing that oth­er com­pa­nies with sim­i­lar­ly tar­get­ed pro­grams have a tri­al size of about 55 pa­tients.

Merus will con­tin­ue to en­roll pa­tients in its clin­i­cal pro­grams even af­ter head­ing to the FDA, when­ev­er that might be, Lund­berg not­ed. He al­so de­murred about ad­vanc­ing the pro­gram in­to a late-stage tri­al, again com­par­ing zeno to how sim­i­lar pro­grams achieved ap­proval based on one sin­gle-arm study.

On the whole, though, the da­ta come as Merus’ part­ner­ship with Lil­ly gets in­to full swing. Back in Jan­u­ary, Lil­ly paid $40 mil­lion in up­front cash and $20 mil­lion in an eq­ui­ty stake to co-de­vel­op three bis­pe­cif­ic an­ti­bod­ies look­ing to en­gage the CD3 anti­gen on T cells. Each pro­gram could net up to $540 mil­lion in de­vel­op­ment and sales, bring­ing the to­tal val­ue of the deal north of $1.6 bil­lion.

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, 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.

By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

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What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

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Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

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David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

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Reshma Kewalramani, Vertex CEO (BIO via YouTube)

UP­DAT­ED: Ver­tex strikes out on its lat­est big shot at a rare ge­net­ic dis­ease. But they're go­ing to keep on swing­ing

It’s been several months since Vertex culled one of its small molecules for alpha-1 antitrypsin deficiency (AATD), taking a big hit after evidence of liver damage surfaced in a key Phase II trial. Now we learned that the company has whiffed on its second shot, and there’s nothing left in the clinic to treat the rare genetic disease — but that won’t stop it from trying.

Despite avoiding the safety issues that plagued the last candidate, Vertex $VRTX is taking the axe to VX-864 after Phase II results revealed the magnitude of the drug’s response is “unlikely to translate into substantial clinical benefit.” As a result of the news, the company’s stock fell 12.5% after hours.

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FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

Paul Hudson, Sanofi CEO (Eric Piermont/AFP via Getty Images)

Months af­ter FDA re­jec­tion, Sanofi touts piv­otal win for rare dis­ease drug su­tim­limab as it preps to re­file

One of the pillar drugs of Sanofi’s $11.6 billion pickup of Bioverativ hit a big setback late last year when the FDA sent its application for approval back. Now, as Sanofi gears up to resubmit the drug for review, the drugmaker is touting pivotal data it hopes will help take it over the finish line.

Sanofi’s sutimlimab nailed all three of its primary endpoints in its Phase III CADENZA study for patients with cold agglutinin disease, a rare disorder that can cause severe anemia, without a recent history of blood transfusion, the French drugmaker said Friday. The topline results will be presented at this weekend’s virtual EHA meeting.

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Ver­tex and CRISPR Ther­a­peu­tics un­veil more pos­i­tive gene ther­a­py da­ta, but busul­fan again casts a shad­ow over the field

Less than 12 hours after revealing a flop on its second shot for alpha-1 antitrypsin deficiency, Vertex plowed ahead with another data drop from its partnership with CRISPR Therapeutics. And though the topline proved positive, concerns over conditioning agents continue to linger over the collaboration, as well as the entire gene therapy space.

Presenting data from two trials at the European Hematology Association annual meeting, the pair announced that follow-up data of at least three months for 22 patients with genetic blood disorders indicated a “consistent and sustained” response to the experimental drug CTX001. All 15 patients with transfusion-dependent beta thalassemia did not need further blood transfusions and all seven with severe sickle cell disease were pain free, the biotechs announced.

Janet Woodcock, acting FDA commissioner, at Thursday's Senate Appropriations hearing (Bill Clark/CQ Roll Call via AP Images)

Sen­a­tors lam­bast new Alzheimer’s drug’s price but give Janet Wood­cock a free pass on the ap­proval de­ci­sion

Senate Finance Democrats took aim at Biogen’s pricey new Alzheimer’s drug on Thursday, but members on both sides of the aisle at a separate appropriations hearing didn’t question acting FDA commissioner Janet Woodcock on the approval.

“I was appalled that Biogen priced their Alzheimer’s drug approved by the FDA at $56,000 per year — I’m not going to debate whether this is effective or not, but it’s double the household median income for Michiganders over the age of 65,” Sen. Debbie Stabenow (D-MI) said at the finance hearing.