Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

Af­ter a busy week­end at #ES­MO21, which in­clud­ed a big read­out for its KRAS drug ada­gra­sib in colon can­cer, Mi­rati Ther­a­peu­tics is ready to keep the pres­sure on com­peti­tor Am­gen with lung can­cer da­ta that will un­der­gird an up­com­ing fil­ing.

In topline re­sults from a Phase II co­hort of its KRYS­TAL-1 study, ada­gra­sib post­ed a re­sponse rate of 43% in sec­ond-line-or-lat­er pa­tients with metasta­t­ic non-small cell lung can­cer con­tain­ing a KRAS-G12C mu­ta­tion, Mi­rati said Mon­day.

It’s the lat­est up­date from the KRYS­TAL study, which is test­ing ada­gra­sib as a monother­a­py and in com­bi­na­tions across mul­ti­ple sol­id tu­mor types. Da­ta from the Phase I por­tion of that study in NSCLC piqued in­vestors’ in­ter­est, with a 45% re­sponse rate that ap­peared to ri­val reg­is­tra­tional da­ta for Am­gen’s so­tora­sib — now ap­proved and mar­ket­ed as Lumakras — in the same in­di­ca­tion.

Now, the Phase II monother­a­py da­ta, which Mi­rati is call­ing “po­ten­tial­ly reg­is­tra­tion-en­abling,” back up those ear­ly re­sults and ap­pear good enough to put ada­gra­sib on the path to ap­proval and in­to a head-to-head com­pe­ti­tion with so­tora­sib. Mi­rati plans to file its NDA for the drug in the fourth quar­ter, the biotech said in a re­lease.

But full re­sults from this co­hort, in­clud­ing com­plete and par­tial re­spons­es and safe­ty da­ta, will have to wait for a med­ical meet­ing ear­ly next year, Mi­rati said. Ada­gra­sib post­ed an 80% dis­ease con­trol rate on June 15 with 98.3% of pa­tients pre­vi­ous­ly treat­ed with im­munother­a­py and chemo.

It’s been a busy week­end at #ES­MO21 for Mi­rati and its clos­est com­peti­tor with com­pet­ing da­ta re­leas­es in col­orec­tal can­cer, which is ex­pect­ed to be the next bat­tle­ground for both drugs. On Sun­day, Mi­rati re­leased da­ta from the Phase II por­tion of KRYS­TAL show­ing so­lo ada­gra­sib post­ed a re­sponse rate of 22% in colon can­cer pa­tients with at least two pri­or lines of ther­a­py, per in­ves­ti­ga­tors, with one un­con­firmed par­tial re­sponse re­port­ed.

The drug post­ed a dis­ease con­trol rate of 87% at a me­di­an 8.9-month fol­low up, with a me­di­an du­ra­tion of re­sponse of 4.2 months and me­di­an pro­gres­sion free sur­vival of 5.6 months.

Mean­while, an ada­gra­sib-ce­tux­imab com­bo post­ed a re­sponse rate of 43% in 28 evalu­able pa­tients with two un­con­firmed par­tial re­spons­es and a dis­ease con­trol rate of 100% at a me­di­an sev­en-month check-in. Af­ter the da­ta cut­off, one of those par­tial re­spons­es was con­firmed, Mi­rati said, while the oth­er PR had pro­gressed.

On Thurs­day, Am­gen un­veiled Phase Ib/II da­ta show­ing a com­bo of so­tora­sib and EGFR in­hibitor Vectibix post­ed an over­all re­sponse rate of 27% in 26 pa­tients with ad­vanced col­orec­tal can­cer with KRAS-G12C. The 27% over­all re­sponse rate in the ini­tial 26 pa­tients, which in­clud­ed five pa­tients who saw tu­mor growth af­ter treat­ment with so­tora­sib monother­a­py, was a far cry bet­ter than the 7.1% re­sponse rate the drug post­ed so­lo in a Phase I test, lat­er up­dat­ed to 9.3%.

In an un­usu­al email late Sun­day, an Am­gen spokesper­son sent a lengthy state­ment point­ing out the dan­gers of cross-tri­al com­par­isons and tout­ing the drug­mak­er’s planned strat­e­gy to pur­sue so­tora­sib com­bi­na­tions for CRC, in­clud­ing a planned third-line-or-lat­er Phase III study.

But on sheer num­bers alone, Mi­rati at the very least looks like a strong com­peti­tor for Lumakras, which hit the mar­ket in NSCLC first and pro­vid­ed proof of con­cept for KRAS in­hibitors on the whole. More da­ta will cer­tain­ly clar­i­fy dif­fer­ences be­tween the drugs, but Mi­rati ap­pears to like where it cur­rent­ly stands.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on clinicaltrials.gov that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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