Preston Klassen, Metacrine CEO

An­oth­er NASH play­er re­treats from bat­tered field af­ter tox­i­col­o­gy study flags po­ten­tial de­lay

NASH, the no­to­ri­ous liv­er dis­ease af­flict­ing an in­creas­ing num­ber of Amer­i­cans, has al­ways been the fo­cus at Metacrine ever since se­r­i­al en­tre­pre­neur Rich Hey­man un­veiled the first round of fi­nanc­ing all the way back in 2015.

Not any­more.

The San Diego-based biotech is halt­ing its NASH pro­gram and choos­ing in­stead to pri­or­i­tize its ef­fort in push­ing the same FXR ag­o­nist, MET642, in­to a Phase II tri­al for in­flam­ma­to­ry bow­el dis­ease.

Metacrine joins a long line of biotechs tak­ing a step back from NASH. Just this year, NGM and Enan­ta have shift­ed fo­cus in the wake of tri­al flops; and that’s fol­low­ing set­backs at Gen­fit, In­ter­cept, CymaBay and Al­bireo.

Ac­cord­ing to Metacrine, pre­lim­i­nary re­sults from a nine-month an­i­mal tox­i­col­o­gy study have flagged the need for a re­view — which will de­ter­mine whether it needs an­oth­er long-term an­i­mal tox­i­col­o­gy study be­fore start­ing Phase III in IBD.

Even though Metacrine called an in­ter­im read­out from a 16-week Phase IIa tri­al pos­i­tive, CEO Pre­ston Klassen sug­gest­ed it’s not worth the “sig­nif­i­cant cap­i­tal and re­sources re­quired” to move in­to a large late-stage tri­al at this time.

“This de­ci­sion was in­flu­enced in part by a po­ten­tial de­lay in con­firm­ing ap­pro­pri­ate safe­ty mar­gins in our long-term tox­i­col­o­gy work that would im­pact the tim­ing of fu­ture NASH stud­ies, but is un­like­ly to im­pact time­lines for the IBD clin­i­cal pro­gram,” he said.

FXR-based ther­a­pies, he added, hold great promise in IBD be­cause of their role in in­testi­nal func­tion. Plus, un­like oth­er ther­a­pies for the dis­ease, it doesn’t come with im­muno­sup­pres­sion.

Still, Metacrine isn’t en­tire­ly giv­ing up on NASH. A 3mg dose of MET642 demon­strat­ed “mean­ing­ful liv­er fat re­duc­tion” and a de­cent tol­er­a­bil­i­ty pro­file — al­though the high­er dose pre­sent­ed a murki­er pic­ture.

The be­lief now, echo­ing the strat­e­gy be­ing pur­sued at bat­tle-test­ed Gilead and No­vo Nordisk, is that treat­ing NASH will like­ly re­quire com­bi­na­tion regimes, Klassen not­ed, of which MET642 can be a part.

“In this small in­ter­im analy­sis, the 6 mg co­hort dis­played a non-nor­mal dis­tri­b­u­tion in liv­er fat changes, as ev­i­denced by dif­fer­ences be­tween the mean and me­di­an re­sults,” he said. “Fur­ther clar­i­fi­ca­tion of the im­pact on liv­er fat at the 6 mg dose will re­quire ex­am­i­na­tion of the com­plete tri­al da­ta set, which is an­tic­i­pat­ed in the first half of 2022.”

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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Seagen interim CEO Roger Dansey and Daiichi Sankyo CEO Sunao Manabe

Paving the way for Mer­ck­'s buy­out, Seagen los­es ar­bi­tra­tion dis­pute with Dai­ichi over ADC tech

As Seagen awaits a final buyout offer from Merck that could be in the territory of $40 billion, Seagen revealed Friday afternoon that it lost an arbitration dispute with Daiichi Sankyo relating to the companies’ 2008 collaboration around the use of antibody-drug conjugate (ADC) technology.

But that loss likely won’t matter much when it comes to Merck’s deal.

After breaking off its pact with Daiichi in mid-2015, the two companies battled over “linker” tech — a chemical bridge between an ADC’s antibody component and the cytotoxic payload — that Seagen claims Daiichi would improve upon and implement in its current generation of ADCs.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

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Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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