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

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

Akero, primarily based in South San Francisco, CA, brings to Novo Nordisk a Part III fibroblast development issue 21 (FGF21) analogue efruxifermin (EFX) that the Danish-based purchaser has trumpeted as a probably best-in-class therapy for MASH. EFX is now in Part III research for the therapy of average to superior liver fibrosis (F2-F3) in addition to for the therapy of cirrhosis (F4).

And Novo Nordisk confirmed how keen it was to get its fingers on EFX, because it agreed to pay upfront 90% of the potential deal worth, or roughly $4.7 billion.

Why pay a lot? One key motive is EFX’s robust scientific knowledge. In January, Akero launched optimistic preliminary topline 96-week knowledge from the Part IIb SYMMETRY trial (NCT05039450) assessing EFX in sufferers with biopsy-confirmed compensated cirrhosis (F4), Little one-Pugh Class A, as a result of MASH.

Information from SYMMETRY confirmed that amongst 134 sufferers with baseline and week 96 biopsies, 39% of the 46 sufferers handled with 50 mg EFX had their cirrhosis reversed with no worsening of MASH vs. 15% of the 47-patient placebo group. Within the trial’s 181-patient Intent to Deal with (ITT) inhabitants, with all lacking week 96 biopsies handled as failures, 29% of sufferers within the 63-patient 50 mg EFX group noticed reversal of cirrhosis with no worsening of MASH, in comparison with roughly 12% within the 61-patient placebo group.

“Main therapy” potential

“It’s the solely FGF21 analogue that has demonstrated fibrosis regression within the late-stage F4 section in a protracted Part II trial,” Novo Nordisk president and CEO Maziar (Mike) Doustdar defined, addressing analysts on a convention name asserting the Akero acquisition. “We subsequently imagine that efruxifermin has the potential to grow to be a number one therapy choice throughout the therapy intensification section of MASH, with efficacy anticipated to outstrip that of incretins as monotherapy in late-stage fibrosis instances.”

Amongst these incretins is Novo Nordisk’s blockbuster weight problems/weight upkeep drug Wegovy® (semaglutide), a glucagon-like peptide 1 (GLP-1) agonist, which in August received further FDA approval to deal with MASH in adults with moderate-to-advanced liver fibrosis (F2-F3). The corporate held off commenting on the success of its launch throughout the name till after it launched third-quarter outcomes.

Wegovy’s approval for MASH was primarily based partially on 72-week knowledge from the Part III ESSENCE trial (NCT04822181) exhibiting 62.9% of individuals handled with semaglutide 2.4 mg achieved decision of steatohepatitis with no worsening of liver fibrosis (vs. 34.3% of placebo sufferers), whereas 36.8% of semaglutide sufferers noticed enchancment in liver fibrosis with no worsening of steatohepatitis (vs. 22.4% on placebo).

In MASH, Wegovy treats the identical adults that had been efficiently handled by Akero with EFX in one other Part IIb trial, HARMONY (NCT04767529). In accordance with knowledge revealed August 14 in The Lancet, in HARMONY’s 126-patient modified intent-to-treat inhabitants, 21 of 43 sufferers (49%) handled with 50 mg of EFX confirmed a ≥1-stage fibrosis enchancment with out MASH worsening vs. 8 of 43 sufferers (19%) within the placebo group.

“Efruxifermin resulted in larger enhancements in fibrosis than placebo after 96 weeks, warranting additional investigation in Part III trials,” researchers concluded.

“General, the MASH market is in its early levels, and we intention to develop a portfolio spanning throughout the illness levels of MASH,” Doustdar added.

Amongst its rivals in MASH is Madrigal Prescription drugs (NASDAQ: MDGL), which final 12 months received an historic accelerated approval for its MASH remedy Rezdiffra™ (resmetirom), the primary drug ever permitted to deal with the illness. Rezdiffra was permitted for the therapy of adults with noncirrhotic MASH with average to superior liver fibrosis (per levels F2 to F3 fibrosis), together with weight-reduction plan and train.

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

One-upping a competitor

Past optimistic knowledge and pipeline constructing, one other key motive for Novo Nordisk’s curiosity in EFX and Akero was an obvious need to one-up a competitor.

Novo Nordisk’s deal comes a month after Roche (SIX Swiss Alternate: ROG) expanded its MASH pipeline past a single Part I candidate, the anti-TL1A monoclonal antibody RG6631 (afimkibart). Roche agreed to shell out as much as roughly $3.5 billion to purchase out 89bio (NASDAQ: ETNB), a deal anticipated to shut this quarter. On the time, one analyst mentioned that the driving force of the deal—89bio’s lead candidate pegozafermin—was one in all two Part III FGF21 analogs for MASH that Roche may have acquired, the opposite being Akero’s EFX.

“With principally two acquisition targets obtainable to Roche within the FGF21 area, we imagine Roche received a relative discount for a late-stage Part III asset,” the analyst, Edward Nash of Canaccord Genuity, wrote in a analysis notice.

Nash adopted up by saying Novo was more likely to find yourself with one of the best FGF21 analog at one of the best value in comparison with Roche and one other biopharma large GlaxoSmithKline (GSK), which in July acquired the lead asset of Boston Prescription drugs, the Part IIb candidate efimosfermin, for as much as $2 billion ($1.2 billion in upfront money, $800 million in milestones).

“Good match? Undoubtedly!”

“A superb match? In our view, positively!” Nash wrote. He famous that GSK and Roche have by no means been often called MASH drug builders.

“That isn’t to say they can’t run profitable trials for a metabolic indication, however MASH is just not one in all their core indications from a enterprise standpoint,” Nash defined. “Novo, alternatively, is by far traditionally and at present some of the lively Pharma gamers within the area throughout a number of mechanisms. We really feel that they’re the proper match for a drug like efruxifermin and positively know the area nicely.”

Buyers didn’t appear fairly as enthused. Akero shares solely jumped 16% on Thursday on information of the Novo Nordisk deal, from $46.49 to $54.08—as an alternative of the one-third or greater surge that corporations sometimes see when area of interest drug builders are acquired by a big-name biopharma. The inventory barely budged Friday, dipping 0.4% to $53.88, then down one other 0.4% to $53.66.

At $54 a share upfront, the Akero-Novo Nordisk affords buyers solely a 16% premium from Wednesday’s shut. Buyers may even obtain a non-transferable contingent worth proper (CVR) entitling them to a different $6 per share if Novo Nordisk wins U.S. regulatory approval of EFX for compensated cirrhosis as a result 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 other 0.7% to DKK 376.95 ($58.34) on Friday, and slid an additional 0.9% to DKK 373.55 ($57.82). That end result means that buyers weren’t as wowed as Novo Nordisk and Doustdar, who inked the corporate’s largest-ever merger-and-acquisition deal by buying 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 inventory remains to be down year-over-year, having nosedived 53% within the 12 months because it closed at DKK 802.50 ($124.64) on October 10, 2024, as buyers stay involved over the aggressive problem posed by rising competitors from rival weight problems and diabetes drug builders.

Novo Nordisk aimed to handle these considerations final month when it laid off about 9,000 of its 78,400 workers, 11.5% of its world workforce.

Akero’s key function in Roche deal

Akero’s optimistic EFX knowledge performed a key function in Roche’s deliberate buyout of 89bio.

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

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

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

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

What adopted had been talks between Roche and 89bio that originally targeted on a producing deal for pegozafermin, then expanded at 89bio’s suggestion into acquisition talks. Each corporations negotiated on a share value earlier than agreeing in the end to as much 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 locations in what’s shaping as much as be a quickly rising marketplace for MASH remedies. That market stood at $2.47 billion final 12 months and is anticipated to broaden at a compound annual development charge of 16.8% to $8.38 billion by 2033, in accordance with Progress Market Studies.

Intellia knowledge lifts gene modifying shares

The previous month has been a bullish one for the shares of gene modifying remedy builders led by Intellia Therapeutics (NASDAQ: NTLA) as its buyers embraced its announcement of optimistic scientific knowledge in hereditary angioedema (HAE) and transthyretin amyloidosis (ATTR)—whereas the great vibes prolonged to the shares of different corporations within the area.

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

Schultes shared knowledge from the Part I/II trial (NCT05120830) exhibiting that lonvoguran ziclumeran (lonvo-z), the gene modifying candidate beforehand referred to as NTLA-2002, efficiently handled HAE by decreasing kallikrein ranges to lower than 60% as much as and past two years after therapy in any respect doses. The 50 mg dose supplied one of the best outcomes among the many 27 sufferers studied in Part II, with 70% of these sufferers exhibiting a whole response.

Lonvo-z for HAE is now below examine within the Part III HAELO trial (NCT06634420), which accomplished affected person enrollment final month. Intellia mentioned it expects to launch topline knowledge within the first half of 2026, then submit a biologics license utility (BLA) within the second half of 2026, and launch lonvo-z within the first half of 2027.

As for ATTR, Schultes offered outcomes from a two-part Part I examine (NCT04601051) of nexiguran ziclumeran (nex-z; previously NTLA-2001) in sufferers with hereditary ATTR amyloidosis with polyneuropathy (ATTRv-PN). The outcomes confirmed that 24 months following therapy, most sufferers skilled enhancements of their modified neuropathy impairment rating—one thing not seen in some other remedies, Schultes emphasised.

Among the many 33 sufferers who obtained a one-time dose of 0.3 mg/kg or greater, the imply serum TTR discount at 24 months was 92% (corresponding imply absolute serum TTR degree of 17.3 g/mL). Among the many 12 sufferers evaluated 36 months following therapy, the imply serum TTR discount was 90% (corresponding imply absolute serum TTR degree of 20 g/mL).

Researchers revealed the leads to The New England Journal of Drugs and plan to complete the trial in 2027.

Schultes characterised the TTR reductions seen in Part I as “fast, deep, constant, and sturdy,” including: “Sufferers are getting higher.”

So too are Intellia shares, which over the previous month have greater than doubled, zooming 108% from $11.42 on September 12, regardless of a 3% drop that despatched shares right down to $23.76 on Monday.

Additionally exhibiting vital one-month positive aspects amongst gene modifying shares:

• Prime Drugs (NASDAQ: PRME)—Up 39% from $4.07 to $5.65
• Editas Drugs (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 corporate mentioned that the FDA granted its Breakthrough Remedy Designation for its next-generation BCL2 inhibitor candidate sonrotoclax for the therapy of adults with relapsed or refractory (R/R) mantle cell lymphoma (MCL). The FDA additionally accepted BeOne’s request for participation in Mission Orbis, an initiative that gives a framework for concurrent submission and evaluation of oncology merchandise amongst collaborating world well being authorities. The FDA primarily based its determination on knowledge from the Part I/II BGB-11417-201 trial (NCT05471843), evaluating sonrotoclax (previously BGB-11417) in adults with R/R MCL, following therapy with a Bruton’s tyrosine kinase inhibitor (BTKi) and anti-CD20 remedy. BeOne mentioned it plans to current full knowledge from the trial at an upcoming medical assembly. Sonrotoclax is now below examine within the Part III confirmatory CELESTIAL-RRMCL trial (NCT06742996). BeOne was previously referred to as BeiGene till its relaunch in Could.
• Tvardi Therapeutics (TVRD) shares cratered 84% from $41.60 to $6.69 on Monday after the corporate reported preliminary knowledge from its Part II REVERT trial (NCT05671835) assessing TTI-101 in idiopathic pulmonary fibrosis (IPF). Tivardi acknowledged {that a} preliminary evaluation of exploratory efficacy confirmed no statistically vital variations between placebo and therapy arms. From baseline to final go to on therapy, the proportion of sufferers who demonstrated pressured important capability (FVC) enchancment from baseline was 41% for the examine’s 24 evaluable placebo sufferers, 39% for the eight evaluable sufferers dosed with 400 mg of TTI-101, and 44% for the 13 evaluable sufferers dosed with 800mg. “Within the combination, we didn’t observe a good thing about TTI-101 therapy on this IPF examine. The restricted knowledge set, excessive variability inside therapy arms, and surprising efficiency of the placebo arm make it troublesome to supply extra definitive conclusions presently,” Tvardi CEO Imran Alibhai, PhD, acknowledged.