Novo Nordisk Raises MASH Wager With Up-to-$5.2B Akero Acquisition

If creating medication for metabolic dysfunction-associated steatohepatitis (MASH) had been a poker sport, you’ll say Novo Nordisk (NASDAQ Copenhagen: NOVO-B) observed a competitor’s wager and raised the stakes with its deliberate up-to-$5.2 billion acquisition of Akero Therapeutics (NASDAQ: AKRO).

Akero, based totally in South San Francisco, CA, brings to Novo Nordisk a Half III fibroblast improvement situation 21 (FGF21) analogue efruxifermin (EFX) that the Danish-based purchaser has trumpeted as a most likely best-in-class remedy for MASH. EFX is now in Half III analysis for the remedy of common to superior liver fibrosis (F2-F3) along with for the remedy of cirrhosis (F4).

And Novo Nordisk confirmed how eager it was to get its fingers on EFX, as a result of it agreed to pay upfront 90% of the potential deal price, or roughly $4.7 billion.

Why pay quite a bit? One key motive is EFX’s strong scientific information. In January, Akero launched optimistic preliminary topline 96-week information from the Half IIb SYMMETRY trial (NCT05039450) assessing EFX in victims with biopsy-confirmed compensated cirrhosis (F4), Toddler-Pugh Class A, on account of MASH.

Info from SYMMETRY confirmed that amongst 134 victims with baseline and week 96 biopsies, 39% of the 46 victims dealt with with 50 mg EFX had their cirrhosis reversed with no worsening of MASH vs. 15% of the 47-patient placebo group. Inside the trial’s 181-patient Intent to Take care of (ITT) inhabitants, with all missing week 96 biopsies dealt with as failures, 29% of victims throughout the 63-patient 50 mg EFX group observed reversal of cirrhosis with no worsening of MASH, compared with roughly 12% throughout the 61-patient placebo group.

“Essential remedy” potential

“It’s the solely FGF21 analogue that has demonstrated fibrosis regression throughout the late-stage F4 part in a protracted Half II trial,” Novo Nordisk president and CEO Maziar (Mike) Doustdar outlined, addressing analysts on a conference title asserting the Akero acquisition. “We subsequently think about that efruxifermin has the potential to develop to be a primary remedy alternative all through the remedy intensification part of MASH, with efficacy anticipated to outstrip that of incretins as monotherapy in late-stage fibrosis cases.”

Amongst these incretins is Novo Nordisk’s blockbuster weight issues/weight repairs drug Wegovy® (semaglutide), a glucagon-like peptide 1 (GLP-1) agonist, which in August obtained additional FDA approval to cope with MASH in adults with moderate-to-advanced liver fibrosis (F2-F3). The company held off commenting on the success of its launch all through the title until after it launched third-quarter outcomes.

Wegovy’s approval for MASH was based totally partially on 72-week information from the Half III ESSENCE trial (NCT04822181) exhibiting 62.9% of people dealt with with semaglutide 2.4 mg achieved determination of steatohepatitis with no worsening of liver fibrosis (vs. 34.3% of placebo victims), whereas 36.8% of semaglutide victims observed enchancment in liver fibrosis with no worsening of steatohepatitis (vs. 22.4% on placebo).

In MASH, Wegovy treats the similar adults that had been effectively dealt with by Akero with EFX in a single different Half IIb trial, HARMONY (NCT04767529). In accordance with information revealed August 14 in The Lancet, in HARMONY’s 126-patient modified intent-to-treat inhabitants, 21 of 43 victims (49%) dealt with with 50 mg of EFX confirmed a ≥1-stage fibrosis enchancment with out MASH worsening vs. 8 of 43 victims (19%) throughout the placebo group.

“Efruxifermin resulted in bigger enhancements in fibrosis than placebo after 96 weeks, warranting extra investigation in Half III trials,” researchers concluded.

“Common, the MASH market is in its early ranges, and we intention to develop a portfolio spanning all through the sickness ranges of MASH,” Doustdar added.

Amongst its rivals in MASH is Madrigal Prescribed drugs (NASDAQ: MDGL), which last 12 months obtained an historic accelerated approval for its MASH treatment Rezdiffra™ (resmetirom), the first drug ever permitted to cope with the sickness. Rezdiffra was permitted for the remedy of adults with noncirrhotic MASH with common to superior liver fibrosis (per ranges F2 to F3 fibrosis), along with weight-reduction plan and prepare.

It’s too early to tell if analyst predictions of Rezdiffra becoming a blockbuster as early as 2026 will come true. The drug generated $180.1 million in product sales last 12 months and $350.052 million throughout the first six months of this 12 months—wanting the billion-dollar-a-year “blockbuster” benchmark.

One-upping a competitor

Previous optimistic information and pipeline developing, one different key motive for Novo Nordisk’s curiosity in EFX and Akero was an apparent have to one-up a competitor.

Novo Nordisk’s deal comes a month after Roche (SIX Swiss Alternate: ROG) expanded its MASH pipeline previous a single Half I candidate, the anti-TL1A monoclonal antibody RG6631 (afimkibart). Roche agreed to shell out as a lot as roughly $3.5 billion to buy out 89bio (NASDAQ: ETNB), a deal anticipated to close this quarter. On the time, one analyst talked about that the driving pressure of the deal—89bio’s lead candidate pegozafermin—was one among two Half III FGF21 analogs for MASH that Roche might have acquired, the other being Akero’s EFX.

“With principally two acquisition targets obtainable to Roche throughout the FGF21 space, we think about Roche obtained a relative low cost for a late-stage Half III asset,” the analyst, Edward Nash of Canaccord Genuity, wrote in a evaluation discover.

Nash adopted up by saying Novo was extra prone to end up with among the best FGF21 analog at among the best worth compared with Roche and one different biopharma giant GlaxoSmithKline (GSK), which in July acquired the lead asset of Boston Prescribed drugs, the Half IIb candidate efimosfermin, for as a lot as $2 billion ($1.2 billion in upfront cash, $800 million in milestones).

“Good match? Undoubtedly!”

“An excellent match? In our view, positively!” Nash wrote. He well-known that GSK and Roche have on no account been usually referred to as MASH drug builders.

“That isn’t to say they’ll’t run worthwhile trials for a metabolic indication, nonetheless MASH is simply not one among their core indications from a enterprise standpoint,” Nash outlined. “Novo, alternatively, is by far historically and at current among the vigorous Pharma avid gamers throughout the space all through various mechanisms. We actually really feel that they’re the correct match for a drug like efruxifermin and positively know the world properly.”

Patrons didn’t seem pretty as enthused. Akero shares solely jumped 16% on Thursday on info of the Novo Nordisk deal, from $46.49 to $54.08—as a substitute of the one-third or better surge that companies typically see when space of curiosity drug builders are acquired by a big-name biopharma. The stock barely budged Friday, dipping 0.4% to $53.88, then down one different 0.4% to $53.66.

At $54 a share upfront, the Akero-Novo Nordisk affords patrons solely a 16% premium from Wednesday’s shut. Patrons might even receive a non-transferable contingent price correct (CVR) entitling them to a special $6 per share if Novo Nordisk wins U.S. regulatory approval of EFX for compensated cirrhosis on account of MASH by June 30, 2031.

Novo Nordisk shares on NASDAQ Copenhagen slipped 1.25% Thursday, from DKK 384.40 ($59.50) to DKK 379.60 ($58.76), dipped one different 0.7% to DKK 376.95 ($58.34) on Friday, and slid a further 0.9% to DKK 373.55 ($57.82). That finish end result implies that patrons weren’t as wowed as Novo Nordisk and Doustdar, who inked the company’s largest-ever merger-and-acquisition deal by shopping for Akero.

Since Doustdar succeeded Lars Fruergaard Jørgensen as CEO on August 7, Novo Nordisk shares have risen 22% from DKK 308.85 ($477.97). Nonetheless, the stock stays to be down year-over-year, having nosedived 53% throughout the 12 months as a result of it closed at DKK 802.50 ($124.64) on October 10, 2024, as patrons keep concerned over the aggressive downside posed by rising opponents from rival weight issues and diabetes drug builders.

Novo Nordisk aimed to deal with these issues last month when it laid off about 9,000 of its 78,400 employees, 11.5% of its world workforce.

Akero’s key perform in Roche deal

Akero’s optimistic EFX information carried out a key perform in Roche’s deliberate buyout of 89bio.

About two weeks after the deal was launched on September 18, 89bio disclosed in a regulatory submitting that it had been in talks with Roche stretching once more to March 2023, when 89bio entered proper right into a nondisclosure settlement with Roche’s Genentech subsidiary to debate “a potential enterprise combination, collaboration, or partnership.”

Genentech was the one agency named among the many many 14 “world and regional biopharmaceutical companies” that had engaged 89bio, in accordance with the October 1 submitting. If Novo Nordisk was amongst these companies, 89bio didn’t say so.

The submitting moreover revealed that Roche stepped up its due diligence into 89bio after seeing Akero’s optimistic MASH information from the SYMMETRY trial.

“Shortly thereafter, representatives of Mom or father [Roche] conveyed that Akero Therapeutics, Inc.’s information had been a optimistic indicator for the class and that Mom or father [Roche] wished to assemble a cross-functional crew to work together in diligence with the intent of exploring a potential collaboration with 89bio,” in accordance with 89bio.

What adopted had been talks between Roche and 89bio that initially focused on a producing deal for pegozafermin, then expanded at 89bio’s suggestion into acquisition talks. Every companies negotiated on a share worth sooner than agreeing in the long run to as a lot as $20.50 ($14.50 upfront, $6 in CVs tied to reaching three milestones).

Roche, like GSK and now Novo Nordisk, is raring to carve out places in what’s shaping as a lot as be a rapidly rising market for MASH treatments. That market stood at $2.47 billion last 12 months and is anticipated to broaden at a compound annual improvement cost of 16.8% to $8.38 billion by 2033, in accordance with Progress Market Research.

Intellia information lifts gene modifying shares

The earlier month has been a bullish one for the shares of gene modifying treatment builders led by Intellia Therapeutics (NASDAQ: NTLA) as its patrons embraced its announcement of optimistic scientific information in hereditary angioedema (HAE) and transthyretin amyloidosis (ATTR)—whereas the nice vibes extended to the shares of various companies throughout the space.

Intellia shares climbed 19% last week, from $20.54 on October 6 to $24.52 on Friday. A variety of the surge consisted of a one-day 20% soar from $20.44 to $24.47 on Wednesday after Birgit Schultes, PhD, Intellia’s authorities vice chairman and CSO, provided updates on three of the company’s ongoing scientific packages at a plenary session all through the European Society of Gene and Cell Treatment (ESGCT)’s Annual Congress, held in Seville, Spain.

Schultes shared information from the Half I/II trial (NCT05120830) exhibiting that lonvoguran ziclumeran (lonvo-z), the gene modifying candidate beforehand known as NTLA-2002, effectively dealt with HAE by reducing kallikrein ranges to decrease than 60% as a lot as and previous two years after remedy the least bit doses. The 50 mg dose provided among the best outcomes among the many many 27 victims studied in Half II, with 70% of those victims exhibiting an entire response.

Lonvo-z for HAE is now under look at throughout the Half III HAELO trial (NCT06634420), which achieved affected particular person enrollment last month. Intellia talked about it expects to launch topline information throughout the first half of 2026, then submit a biologics license utility (BLA) throughout the second half of 2026, and launch lonvo-z throughout the first half of 2027.

As for ATTR, Schultes provided outcomes from a two-part Half I look at (NCT04601051) of nexiguran ziclumeran (nex-z; beforehand NTLA-2001) in victims with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The outcomes confirmed that 24 months following remedy, most victims expert enhancements of their modified neuropathy impairment score—one factor not seen in another treatments, Schultes emphasised.

Among the many many 33 victims who obtained a one-time dose of 0.3 mg/kg or better, the indicate serum TTR low cost at 24 months was 92% (corresponding indicate absolute serum TTR diploma of 17.3 g/mL). Among the many many 12 victims evaluated 36 months following remedy, the indicate serum TTR low cost was 90% (corresponding indicate absolute serum TTR diploma of 20 g/mL).

Researchers revealed the results in The New England Journal of Medicine and plan to finish the trial in 2027.

Schultes characterised the TTR reductions seen in Half I as “quick, deep, fixed, and durable,” together with: “Victims are getting larger.”

So too are Intellia shares, which over the earlier month have better than doubled, zooming 108% from $11.42 on September 12, no matter a 3% drop that despatched shares proper right down to $23.76 on Monday.

Moreover exhibiting very important one-month optimistic features amongst gene modifying shares:

• Prime Medicine (NASDAQ: PRME)—Up 39% from $4.07 to $5.65
• Editas Medicine (NASDAQ: EDIT)—Up 32% from $2.69 to $3.56
• CRISPR Therapeutics (NASDAQ: CRSP)—Up 21% from $56.26 to $68.29

Leaders and laggards

• BeOne Medicines (OTC Pink: BEIGF) shares rocketed 70% from $15.95 to $27.05 on Monday after the company talked about that the FDA granted its Breakthrough Treatment Designation for its next-generation BCL2 inhibitor candidate sonrotoclax for the remedy of adults with relapsed or refractory (R/R) mantle cell lymphoma (MCL). The FDA moreover accepted BeOne’s request for participation in Mission Orbis, an initiative that offers a framework for concurrent submission and analysis of oncology merchandise amongst collaborating world nicely being authorities. The FDA based totally its dedication on information from the Half I/II BGB-11417-201 trial (NCT05471843), evaluating sonrotoclax (beforehand BGB-11417) in adults with R/R MCL, following remedy with a Bruton’s tyrosine kinase inhibitor (BTKi) and anti-CD20 treatment. BeOne talked about it plans to present full information from the trial at an upcoming medical meeting. Sonrotoclax is now under look at throughout the Half III confirmatory CELESTIAL-RRMCL trial (NCT06742996). BeOne was beforehand known as BeiGene until its relaunch in May.
• Tvardi Therapeutics (TVRD) shares cratered 84% from $41.60 to $6.69 on Monday after the company reported preliminary information from its Half II REVERT trial (NCT05671835) assessing TTI-101 in idiopathic pulmonary fibrosis (IPF). Tivardi acknowledged {{that a}} preliminary analysis of exploratory efficacy confirmed no statistically very important variations between placebo and remedy arms. From baseline to last go to on remedy, the proportion of victims who demonstrated pressured necessary functionality (FVC) enchancment from baseline was 41% for the look at’s 24 evaluable placebo victims, 39% for the eight evaluable victims dosed with 400 mg of TTI-101, and 44% for the 13 evaluable victims dosed with 800mg. “Inside the mixture, we didn’t observe a benefit of TTI-101 remedy on this IPF look at. The restricted information set, extreme variability inside remedy arms, and stunning effectivity of the placebo arm make it troublesome to produce further definitive conclusions presently,” Tvardi CEO Imran Alibhai, PhD, acknowledged.