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.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Gos­samer’s Fa­heem Has­nain de­fends a round of pos­i­tive PAH da­ta as a clear win. But can these PhII re­sults stand up to scruti­ny?

Gossamer Bio $GOSS posted a statistically significant improvement for its primary endpoint in the key Phase II TORREY trial for lead drug seralutinib on Tuesday morning. But CEO Faheem Hasnain has some explaining to do on the important secondary of the crucial six-minute walk distance test — which will be the primary endpoint in Phase III — as the data on both endpoints fell short of expectations, missing one analyst’s bar on even modest success.

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Spe­cial re­port 2022: Meet 20 women blaz­ing trails in bio­phar­ma R&D

When you run a special report for a fourth year, it can start feeling a little bit like a ritual. You go through the motions — in our case opening up nominations for top women in biopharma R&D and reviewing more than 500 entries — you make your choices of inclusion and exclusion. You host a ceremony.

But then things happen that remind you why you do it in the first place. Perhaps a Supreme Court rules to overturn the constitutional right to abortion and a group of women biotech leaders makes it clear they strongly dissent; perhaps new data on gender diversity in the industry come out that look all too similar to the old ones, suggesting women are still dramatically underrepresented at the top; perhaps protests and conflicts around the world put in stark terms the struggles that many women still face in earning the most basic recognition.

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Mark McKenna, Prometheus Biosciences chairman & CEO

With clear PhII win in IBD, Prometheus thwarts Pfiz­er com­par­isons as it fol­lows Hu­mi­ra 'play­book'

Prometheus Biosciences reported a clear Phase II win in two inflammatory bowel disease conditions in a clinical development race with Pfizer, planting the biotech’s flag in a field of antibodies attempting to go against black box-cornered JAK inhibitors and AbbVie’s Humira.

Shares $RXDX have soared since the summer — a small dip last week notwithstanding when rival Pfizer teamed up with Roivant on a new company for their competing anti-TL1A monoclonal antibody. And they skyrocketed once again Wednesday morning, climbing from $36 apiece to more than $100 on the back of two Phase II studies: one placebo-controlled in ulcerative colitis and the other an open-label trial in patients with Crohn’s disease.

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Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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Graphic: Shutterstock

Prometheus moves to raise cash hours af­ter PhII da­ta leads to stock surge

After releasing better-than-anticipated data on two mid-stage studies Wednesday morning, Prometheus Biosciences’ CEO said the company would “take some time to assess” its next financing options.

It only needed about seven hours. Wednesday afternoon after the market closed, the biotech announced it would seek $250 million through an equity offering as the company looks to edge out anti-TL1A competitor Pfizer and its new partner Roivant.

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Piper Trelstad, head of CMC, Bill & Melinda Gates Medical Research Institute

Q&A with Gates leader: Women tak­ing on more roles in phar­ma man­u­fac­tur­ing, but still work to do

More and more women are driving innovation and taking leadership roles in biotech – as evidenced today in the release of Endpoints News’ list of the top 20 women in the R&D world – but those gains are beginning to extend across pharma sectors.

In pharma manufacturing in the US today, around 46% of all roles are occupied by women, according to the US Bureau of Labor Statistics for 2021. And according to a Bloomberg report, women’s roles across manufacturing roles had a massive boost after the start of the pandemic.

Phar­ma rep­u­ta­tion re­tains 'halo' even as pan­dem­ic me­dia cov­er­age re­cedes — sur­vey

The Covid-19 halo effect on the pharma industry is continuing, according to a new global study from Ipsos. The annual survey for the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) finds considerable goodwill from consumers across measures of trust, cooperation with governments, and advancing research and drug development.

“Despite the pandemic in many countries no longer being the top of mind concern generally – although it does remain the top concern as a health issue – the industry’s reputation has remained positive,” said Ipsos research director Thomas Fife-Schaw.

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FDA commissioner Robert Califf (Jose Luis Magana/AP Images)

FDA pulls On­copep­tides' Pepax­to in­di­ca­tion, open­ing the door for dan­gling ac­cel­er­at­ed ap­proval en­force­ment

In a move all but ensured after an overwhelmingly negative adcomm vote this September, the FDA is yanking Oncopeptides’ dangling accelerated approval. And there may be more to come.

In recent months, US regulators have honed in on reforming the accelerated approval pathway and preventing drugmakers from continuing to sell their medicines in the event of a confirmatory study flop. The moves come after commissioner Rob Califf has called for companies to do more to produce post-marketing evidence quickly earlier this year.

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