With crucial lessons learned from the manufacturing shortages of injectable GLP-1s, experts say securing adequate supply of the upcoming oral options will be the sector’s next great challenge.
As Novo Nordisk and Eli Lilly begin to put the challenges they faced stocking their blockbuster weight loss drugs behind them, the next great manufacturing challenge is lurking: orals.
Lilly is already taking action to stockpile doses of its oral GLP-1 candidate orforglipron, spending $550 million to manufacture commercial quantities well ahead of potential approval. The drug is currently undergoing Phase III trials for both type 2 diabetes and obesity, with eagerly anticipated readouts expected later this year.
Even companies with weight loss candidates earlier in development are already planning well in advance. Viking Therapeutics, for example, signed a long-term partnership this month with CordenPharma to produce 1 billion tablets of the investigational oral weight loss drug VK2735, as well as 100 million autoinjectors and 100 million vial and syringe products of an injectable version of the asset. The oral version is currently in Phase II while Viking plans to kick off a Phase III trial for the injectable later this year. Similarly, weight loss startup Metsera has already secured manufacturing capacity despite only being in Phase I.
“What’s coming next, in terms of treatment options, are oral versions . . . for which manufacturing will be simpler,” Chris Shibutani, a senior analyst at Goldman Sachs, said on a 2023 podcast. “Oral versions will enhance the ability to supply a broader, potentially, global market. Several companies, with Lilly and Novo in the lead, are recognizing that is where the puck will go.”
Simpler To Take and To Manufacture
Both Novo and Lilly faced unprecedented demand for their injectable GLP-1s—Wegovy and Zepbound, respectively—and have been attempting to scale up their capabilities as quickly as their capital reserves allow . Novo essentially received an entirely new company to boost capacity as quickly as possible, with Novo Holdings’ $16.5 billion acquisition of Catalent last year. Lilly, meanwhile, has also bolstered manufacturing capacity.
With both drugs now off the FDA’s shortage list, supply constraints have eased. But neither are available in all the countries they have been approved in. The companies have been launching slowly to ensure they have the correct amount of starter doses and maintenance doses for new patients.
One of the reasons injectable GLP-1 peptides are difficult to manufacture and scale is the need for a sterile production environment, Mimoun Ayoub, global head, peptides and oligonucleotides platforms at CordenPharma, told BioSpace. This demands specialist manufacturing facilities set up specifically for the peptides, which has resulted in both Lilly and Novo investing significant capital into additional capacity. In addition, manufacturing injectable GLP-1s requires sufficient production of the injector pens and vials.
The specialized nature of producing these peptides has led to some quality control issues with compounders. Drug developers like Novo and Lilly have suggested that the manufacturing process is too complex for them to handle.
That also means that the number of contract manufacturing organizations (CMOs) capable of providing end-to-end manufacturing at high capacity is relatively limited. Catalent was one of them. Novo Holdings’ acquisition led to a squabble among executives over whether the deal was anti-competitive.
A report by Roots Analysis published in 2020 found that around 50 CMOs provided peptide services, but just 46% of these were capable of producing both peptide active pharmaceutical ingredients (APIs) and finished dose formulation peptides, with only 5% able to provide fill/finish services. The intervening years have witnessed a boom in investment by CMOs providing these services, however, this will take time to come online.
