GLP-1 Injectables Will Quickly Be Joined by Orals. Is the Business Able to Scale?

As Novo Nordisk and Eli Lilly start to place the challenges they confronted stocking their blockbuster weight reduction medication behind them, the subsequent nice manufacturing problem is lurking: orals.

Lilly is already taking motion to stockpile doses of its oral GLP-1 candidate orforglipron, spending $550 million to fabricate business portions nicely forward of potential approval. The drug is at the moment present process Section III trials for each sort 2 diabetes and weight problems, with eagerly anticipated readouts anticipated later this yr.

Even firms with weight reduction candidates earlier in growth are already planning nicely prematurely. Viking Therapeutics, for instance, signed a long-term partnership this month with CordenPharma to supply 1 billion tablets of the investigational oral weight reduction drug VK2735, in addition to 100 million autoinjectors and 100 million vial and syringe merchandise of an injectable model of the asset. The oral model is at the moment in Section II whereas Viking plans to kick off a Section III trial for the injectable later this yr. Equally, weight reduction startup Metsera has already secured manufacturing capability regardless of solely being in Section I.

“What’s coming subsequent, when it comes to remedy choices, are oral variations . . . for which manufacturing will probably be easier,” Chris Shibutani, a senior analyst at Goldman Sachs, mentioned on a 2023 podcast. “Oral variations will improve the flexibility to provide a broader, doubtlessly, international market. A number of firms, with Lilly and Novo within the lead, are recognizing that’s the place the puck will go.”

Less complicated To Take and To Manufacture

Each Novo and Lilly confronted unprecedented demand for his or her injectable GLP-1s—Wegovy and Zepbound, respectively—and have been trying to scale up their capabilities as rapidly as their capital reserves enable . Novo basically acquired a wholly new firm to spice up capability as rapidly as attainable, with Novo Holdings’ $16.5 billion acquisition of Catalent final yr. Lilly, in the meantime, has additionally bolstered manufacturing capability.

With each medication now off the FDA’s scarcity record, provide constraints have eased. However neither can be found in all of the nations they’ve been authorised in. The businesses have been launching slowly to make sure they’ve the right amount of starter doses and upkeep doses for brand spanking new sufferers.

One of many causes injectable GLP-1 peptides are troublesome to fabricate and scale is the necessity for a sterile manufacturing surroundings, Mimoun Ayoub, international head, peptides and oligonucleotides platforms at CordenPharma, instructed BioSpace. This calls for specialist manufacturing services arrange particularly for the peptides, which has resulted in each Lilly and Novo investing vital capital into extra capability. As well as, manufacturing injectable GLP-1s requires enough manufacturing of the injector pens and vials.

The specialised nature of manufacturing these peptides has led to some high quality management points with compounders. Drug builders like Novo and Lilly have steered that the manufacturing course of is simply too complicated for them to deal with.

That additionally signifies that the variety of contract manufacturing organizations (CMOs) able to offering end-to-end manufacturing at excessive capability is comparatively restricted. Catalent was one in every of them. Novo Holdings’ acquisition led to a squabble amongst executives over whether or not the deal was anti-competitive.

A report by Roots Evaluation printed in 2020 discovered that round 50 CMOs offered peptide companies, however simply 46% of those have been able to producing each peptide lively pharmaceutical elements (APIs) and completed dose formulation peptides, with solely 5% capable of present fill/end companies. The intervening years have witnessed a growth in funding by CMOs offering these companies, nevertheless, this can take time to come back on-line.

In response to Matt Phipps, a associate at William Blair, the complexity of peptide manufacturing presents a barrier to new entrants within the weight reduction drug market.

“Are fast-followers going to wish to spend $10 billion to have a facility that will probably be prepared in 4 years which will produce an injectable solely just like Novo Nordisk and Lilly’s therapies?” he requested. That is the place oral GLP-1 therapies could maintain the benefit as a result of CMOs may have the capability to satisfy the demand for such therapies.

In distinction to the complicated manufacturing of injectable peptide-based medication, “the manufacturing course of for oral GLP-1s is less complicated and extra simple, using commonplace strong dose manufacturing belongings with excessive throughput,” Ayoub defined. CMOs may have a better capability to assist manufacture for oral therapies as a result of the processes concerned use commonplace strong dose manufacturing tools for small molecule drugs, he added. A reported 281 CMOs have capabilities in strong dose manufacturing, based on GlobalData.

Oral GLP-1s will have to be taken not less than as soon as day by day in comparison with the once-weekly remedy schedules of Lilly’s Zepbound and Novo’s Wegovy, which means many extra doses will have to be created. Even so, high-throughput manufacturing capabilities, which might enable for many 1000’s to hundreds of thousands of tablets to be produced per hour, will enable for this demand to be met, Ayoub added.

A spokesperson for Novo Nordisk confirmed with BioSpace plans to file for FDA approval of its oral semaglutide remedy Rybelsus in weight reduction within the coming months. The corporate can be creating the oral amycretin. Novo may have a pleasant heads up on the manufacturing problem as a result of it already markets Rybelsus, which turned the primary oral remedy for sort 2 diabetes when it acquired FDA approval in 2019.

Larger Capability, Larger Affected person Inhabitants

There will probably be competitors amongst CMOs trying to appeal to potential oral GLP-1 drug builders, creating a wholly completely different market to the injectable aspect of GLP-1s, Ayoub predicted.

One space that might assist set CMOs aside,Ayoub acknowledged, is the flexibility to extend oral bioavailability or enhance stability, because the physique’s capability to soak up the oral variations of those medication is a possible barrier to make use of. He added that CordenPharma is working to extend oral bioavailability and cut back API quantity in formulations via hydrophobic ion pairing and lipid-based formulations.

The capability of drug builders and the CMO trade to scale manufacturing for oral GLP-1s will depend upon the extent of demand. With its $550 million stockpiling funding, Lilly is hoping to “meet anticipated future demand,” an organization spokesperson instructed BioSpace. Sufferers in lots of markets favor oral medicines over injectables and their manufacture and distribution is simpler, which “lends itself to international scaling,” the spokesperson mentioned.

Analysts like Phipps are cut up on how the market will settle between orals and injectables. “Some folks very a lot assume that it has to go to an oral strategy as a result of that simply holds so many manufacturing benefits, and will serve a wider affected person inhabitants,” he mentioned.

Ought to the oral strategy find yourself being the one reaching probably the most sufferers, CMOs would face main stress on capability. Within the case of CordenPharma, Ayoub mentioned the corporate may rapidly leverage present area at its manufacturing websites to broaden capability to satisfy any demand that grew “far past our expectations.”

Judging by Viking and Metsera’s outlays into manufacturing, smaller gamers needs to be higher positioned to determine aggressive manufacturing capability in orals than with injectables, whether or not via in-house manufacturing or via CMOs. Finally, this might enable the GLP-1 market to open up past the present duopoly.