FDA slaps par­tial hold on Macro­Gen­ics for bis­pe­cif­ic can­cer tri­als as liv­er tox spurs safe­ty fears

Leery about signs of liv­er tox­i­c­i­ty among pa­tients tak­ing a B7-H3 × CD3 bis­pe­cif­ic un­der de­vel­op­ment at Macro­Gen­ics $MGNX, the FDA has slapped a par­tial hold on the ear­ly-stage pro­gram.

The par­tial hold — which af­fects their monother­a­py tri­al as well a com­bi­na­tion ef­fort with their own PD-1 check­point MGA012, part­nered with In­cyte — will stop re­searchers from re­cruit­ing new pa­tients, but peo­ple who have al­ready signed up can con­tin­ue treat­ment.

Scott Koenig

Macro­Gen­ics was quick to down­play the move, not­ing that signs of el­e­vat­ed transam­i­nas­es in the sin­gle-drug study were quick­ly re­solved. And the biotech got some quick help from an­a­lysts, who haven’t been pay­ing all that much at­ten­tion to this pro­gram’s par­tic­u­lar po­ten­tial. CD3, though, plays a promi­nent role in some lead­ing bis­pe­cif­ic ef­forts, and the an­a­lysts would like to know more if the prob­lem here may ex­tend to oth­er de­vel­op­ers.

Macro­Gen­ics has been test­ing this bis­pe­cif­ic in pa­tients with non-small cell lung, blad­der and head and neck can­cer, mesothe­lioma, melanoma, and oth­er B7-H3 pos­i­tive tu­mors.

Jonathan Chang

Leerink’s Jonathan Chang passed along man­age­ment’s con­fi­dence that it can get past this hitch in short or­der and has al­ready pitched a new plan to boost sup­port­ive care in the tri­als.

Over­all, man­age­ment seemed bull­ish that the par­tial clin­i­cal hold could be lift­ed as ear­ly as Jan­u­ary 2019 based on the reg­u­la­to­ry dis­cus­sions so far and the changes be­ing pro­posed, in our view. Man­age­ment in­di­cat­ed that liv­er func­tion test (LFT) el­e­va­tions were ini­tial­ly ob­served in the Q2 week­ly dos­ing reg­i­men, which re­solved with a re­duc­tion in dose. How­ev­er, LFT el­e­va­tions were then ob­served in a cou­ple more pa­tients at a low­er dose.

Umer Raf­fat at Ever­core ISI is in the group that wants to learn more AS­AP.

We sus­pect the liv­er tox in the B7-H3 x CD3 DART may be ON-tar­get tox of this spe­cif­ic com­bi­na­tion. Al­though the com­pa­ny says B7-H3 ex­pres­sion is high in sol­id tu­mors and min­i­mal in nor­mal tis­sues, oth­er sources (see an im­age from the Hu­man Pro­tein At­las at bot­tom) sug­gest B7-H3 (aka CD276) has medi­um to high ex­pres­sion in var­i­ous tis­sues, in­clud­ing the liv­er… If nor­mal cells al­so ex­press B7-H3, then this DART may in­duce more im­mune ac­ti­va­tion than ex­pect­ed, in non-tu­mor en­vi­ron­ments like the liv­er. This is just a hy­poth­e­sis, and we need to see fur­ther clin­i­cal da­ta on safe­ty – it’s hard to make a de­fin­i­tive call giv­en the lim­it­ed de­tail we’ve seen thus far.

“As we’ve iden­ti­fied to the FDA, we be­lieve that transamini­tis ob­served in pa­tients ad­min­is­tered MGD009 was like­ly a cy­tokine-me­di­at­ed event,” not­ed CEO Scott Koenig in a state­ment. “We are work­ing with the FDA and will pro­vide an up­date when we have ad­di­tion­al in­for­ma­tion. This par­tial clin­i­cal hold does not im­pact on­go­ing clin­i­cal stud­ies for enobli­tuzum­ab and MGC018, our oth­er B7-H3-tar­get­ed mol­e­cules.”

Illustration: Assistant Editor Kathy Wong for Endpoints News

How Pur­due's $272M ad­dic­tion pay­out fund­ed a new home for its dis­card­ed non-opi­oid re­search

Don Kyle spent more than 20 years working for Purdue Pharma, right through the US opioid epidemic that led to the company’s rise and eventual infamy. But contrary to Purdue’s focus on OxyContin, Kyle was researching non-opioid painkillers — that is, until the company shelved his research.

As the company’s legal troubles mounted, Kyle found an unlikely way to reboot the project. In 2019, he took his work to an Oklahoma State University center that’s slated to receive more than two-thirds of the state’s $272 million settlement with Purdue over claims that the drugmaker’s behavior ignited the epidemic of opioid use and abuse.

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President Joe Biden at the State of the Union address with Vice President Kamala Harris and House Speaker Kevin McCarthy (Patrick Semansky/AP Images)

The drug pric­ing pres­i­dent: Biden warns of ve­to for any IRA re­peal at­tempts

President Joe Biden made clear in his “finish the job” State of the Union address last night that one of those jobs to be finished is insulin prices.

Biden’s push again to tackle insulin prices, after Republicans rebuffed the idea last summer and just after Biden won Medicare drug price negotiations/caps via the Inflation Reduction Act, shows how heavily he’s leaning into this work.

Rupert Vessey, Bristol Myers Squibb head of research and early development

Up­dat­ed: R&D tur­bu­lence at Bris­tol My­ers now in­cludes the end of a $650M al­liance and the de­par­ture of a top re­search cham­pi­on

This morning biotech Dragonfly put out word that Bristol Myers Squibb has handed back all rights to its IL-12 clinical-stage drug after spending $650 million to advance it into the clinic.

The news arrives amid a turbulent R&D stage for the pharma giant, which late last week highlighted Rupert Vessey’s decision to depart this summer as head of early-stage R&D following a crucial three-year stretch after he jumped to Bristol Myers in the big Celgene buyout. During that time he struck a series of deals for Bristol Myers, and also shepherded a number of Celgene programs down the pipeline, playing a major role for a lineup of biotechs which depended on him to champion their drugs.

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Bill Haney, Dragonfly CEO (Dave Pedley/Getty Images for SXSW)

Drag­on­fly chief: Bris­tol My­ers shouldn’t blame IL-12’s clin­i­cal per­for­mance for de­ci­sion to scrap the deal — eco­nom­ics played a key role

Bristol Myers Squibb says the IL-12 drug they were developing out of Dragonfly Therapeutics was scrubbed from the pipeline for a simple reason: It didn’t measure up on clinical performance.

But Bill Haney, the CEO of Dragonfly, is taking issue with that.

The early-stage drug, still in Phase I development, has passed muster with Bristol Myers’ general clinical expectations, advancing successfully while still in Phase I, he says.

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Utpal Koppikar, new Verily CFO

Ex­clu­sive: Ver­i­ly wel­comes Atara Bio­ther­a­peu­tics vet­er­an as new CFO

Verily, Alphabet’s life sciences outfit, has plucked a new CFO from the ranks of Atara Biotherapeutics, the company announced on Wednesday.

Utpal Koppikar joins Verily after a nearly five-year stint as CFO and senior VP at Atara, though his résumé also boasts roles at Gilead and Amgen.

The news follows a major reshuffling at Verily, including several senior departures earlier this year and a round of layoffs.

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Singer Nick Jonas is back at work for Dexcom, this time for its new G7 glucose monitor.

Dex­com's spokescelebri­ty Nick Jonas re­turns to Su­per Bowl in new glu­cose mon­i­tor com­mer­cial

Dexcom is going back to the Super Bowl with its pop singer and patient spokesperson Nick Jonas. Jonas takes center stage as the lone figure in the 30-second commercial showcasing Dexcom’s next-generation G7 continuous glucose monitoring (CGM) device.

Jonas’ sleight-of-hand tricks populate the commercial — he pinches his empty fingers together and pops them open to reveal the small CGM — even as he ends the ad, saying, “It’s not magic. It just feels that way.” Jonas then disappears in a puff of smoke.

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Richard Francis, newly-appointed Teva CEO (Novartis via Facebook)

New Te­va CEO Richard Fran­cis repri­or­i­tizes to 'get back to growth'

Six weeks into his new role at the helm of Teva Pharmaceutical, Richard Francis said it’s time to “get back to growth,” starting with a good look at the company’s priorities.

The chief executive has kicked off a strategic review, he announced during Teva’s quarterly call, which will continue over the next several months and produce results sometime in the middle of 2023. That means some pipeline cuts may be in store, he told Endpoints News, while declining to offer much more detail.

FDA Commissioner Robert Califf on Capitol Hill, Feb. 8, 2023 (Drew Angerer/Getty Images)

FDA com­mis­sion­er floats ideas on how to bet­ter han­dle the pan­dem­ic

FDA Commissioner Rob Califf joined the heads of the CDC and NIH in the hot seat today before a key House subcommittee, explaining that there needs to be a much faster, more coordinated way to oversee vaccine safety, and that foreign biopharma inspections, halted for years due to the pandemic, are slowly ramping up again.

Califf, who stressed to the House Energy and Commerce’s Subcommittee on Health that the CDC also needs better data, made clear that the FDA’s ability to monitor the safety of vaccines “would also benefit greatly by a coordinated federal public health data reporting authority.”

Sanofi is renewing its #VaccinesForDreams campaign with more stories, such as Juan's in Argentina (Sanofi)

Sanofi re­news so­cial cam­paign to re­mind that vac­cines let peo­ple ‘Dream Big’

Sanofi is highlighting people’s dreams — both big and small — to make the point that vaccines make them possible.

The renewed “Dream Big” global social media campaign’s newest dreamer is Juan, a teacher in the Misiones rainforest in Argentina whose story is told through videos on Instagram and Sanofi’s website with the hashtag #VaccinesForDreams.

The campaign ties to Sanofi’s broader umbrella initiative “Vaccine Stories” to promote the value of vaccines and drive awareness of the need for improved vaccination coverage.

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