Patent protection for semaglutide, the active ingredient in Novo Nordisk’s blockbuster diabetes and weight loss drugs, has ended in several countries. This has stimulated a rush to introduce cheaper generic versions of Ozempic for diabetes and Wegovy for weight management – initially in India and Canada, but with several other countries soon to follow.
In India, 10 generics manufacturers are already making semaglutide injectable pens, while three others are formulating it in vials to be administered with a syringe and needles. This includes firms such as Lupin, Eris, Sun Pharma and Glenmark, with most of the active pharmaceutical ingredient (API) manufactured in China, by firms such as Sinopep, and in India. ‘China is very big in this space because [it] invested very heavily in peptide manufacturing,’ says Markus Felgenhauer, chief executive of Qyobo, which tracks pharmaceutical supply chains.
Indian multinational generics firm Dr Reddy’s Laboratories launched the first semaglutide generic injection in India in March. Health Canada authorised Dr Reddy’s semaglutide in April and noted that it was reviewing eight other submissions. Canada approved its first generic semaglutide injection for weight loss from Canadian-based Apotex in June. Generics also entered the market in Brazil in May, and will likely launch in China next year. Patent protection for semaglutide will remain in place in the US and Europe into the 2030s.
Quality control
However, in July, it was reported that Dr Reddy’s semaglutide manufacturing had run into difficulties, with impurity problems in some batches. Supplies are expected to be unavailable in India and disrupted in Canada until at least October, putting at risk its aim to sell 12 million injectable pens in the first year. Separately, Torrent Pharmaceuticals reportedly also recalled batches of its generic semaglutide injector pens in July. While it is expected that – between all the various emerging suppliers – there will be no problems meeting customer demand, these issues highlight the complexity of manufacturing the drug.
Semaglutide is a modified analogue of the natural human hormone GLP-1. It is made chemically using solid-phase peptide synthesis to sequentially construct the backbone of 31 amino acids, with a fatty acid added at position 26. Manufacturing at scale can be somewhat challenging, with lots of possible ways to go wrong, says Mansoor Amiji from Northeastern University in Boston, US, but it is still more akin to making a small molecule than a biological drug. ‘You could have a few amino acids not [incorporated into] the peptide still present as impurities, or the lipid may not be conjugated but free,’ says Amiji.
The generics market is dominated by price. Resilience by having multiple suppliers is not incentivised
Generic manufacturers must follow regulations of the country where their medicines are sold. Amiji has some concerns about quality control because of the sheer number of companies entering the Indian market, and already there have been some recalls or production faults. However, ‘generics have to abide by the same laws as the brand name, whereas compounding pharmacies and internet-based sellers work in a different world, which is where concerns around quality assurance crop up,’ Amiji adds. Compounding pharmacies selling semaglutide took off in the US during shortages of the Novo Nordisk products and Eli Lilly’s related tirzepatide (Mounjaro and Zepbound) as the companies struggled to scale up production fast enough to meet demand.
Competition in the market is expected to be heated. ‘We’ve seen that some big players have not been part of the first launch of generics in India because they said this is going to be a bloodbath,’ says Felgenhauer, meaning severe pressure on pricing and profitability. He expects that competition to push down prices and, in time, drive some manufacturers out of the market. ‘The generics market is dominated by price,’ he says. ‘Resiliencey by having multiple suppliers is not incentivised because you split volumes and lose economies of scale.’
In response, Novo has lowered its prices in India, and has also licensed Emcure Pharmaceuticals to market semaglutide injections in India, priced midway between the emerging generics and Novo’s branded medicines. ‘When the first generic comes out, the price drops about 33%. With a third generic, it can drop 65–70%,’ says Jennifer Lake from the University of Toronto in Canada.
While generics tussle for market share of injectable semaglutide, Novo and Lilly have both introduced daily tablet drugs. ‘There is an assumption that orals are going to win the game because injections are not desirable for many,’ says Felgenhauer. In January, Novo launched a Wegovy pill in the US – rebranding and extending dosage ranges of its Rybelsus diabetes treatment. The tablets’ formulation protects the semaglutide peptide from degradation in the stomach, although patients must take it on an empty stomach and wait before eating or drinking. In India, since patents only covered the active ingredient and not the formulations, Torrent was able to launch generic semaglutide pills for obesity and diabetes in March, alongside its injectable versions.
Then, in April, Lilly introduced Foundayo (orforglipron) in the US. This is a small molecule, making it fundamentally more suited to an oral pill than a peptide. Analysts forecast that Wegovy’s head start will allow it gain revenues this year, but Lilly’s Foundayo will gain a larger share with time. ‘Historically people don’t want to self-administer injectable medicines,’ says Lake. ‘It is interesting to see these new oral medicines enter the market.’
No comments yet