As we write the 2022 edition of ANDA approvals analysis, the most striking observation is the reversal of the declining trend witnessed over the last couple of years. As a testimony to the unrelenting interest in the area, a total of 742 ANDA approvals were granted during the calendar year 2022, registering a growth of 17 per cent over last year. Additionally, 136 Tentative Approvals were also granted, again a similar growth over 2021 numbers (117) as seen for final ANDA approvals. Indian players contributed a large proportion of the incremental number of approvals this year with 88 more approvals than last year.
Regional trend: Indian companies further consolidate their share; Chinese companies retain the same pace as last year
Similar to our analysis last year, ANDA applicants were mapped to the parent company as recorded in the FDA database and the location/headquarters of the parent company was used for analysing the regional trends. It was no surprise that the Indian companies again dominated the ANDA approvals, with 355 or 48 per cent of total ANDA approvals, further consolidating their share from 42 per cent (267 approvals) from last year. This represents a 33 per cent growth of ANDA approvals for Indian companies versus 2021. India was followed by the US, China, Europe, and Israel, in that order, in the number of ANDA approvals. Chinese companies (without Taiwan) gained 61 approvals during the year (vs 66 last year), maintaining their interest in the US formulations space. Our prediction of increasing interest of Bangladeshi companies in this area started showing up in numbers with five different companies garnering a total of nine approvals, up from one approval for Beximco last year. We expect a steadily increasing two-digit representation of Bangladesh in the future years as well. Notably, there was one approval from Malaysia as well this year with Novugen Oncology SdnBhd getting approval for Abiraterone acetate tablets.
Expectedly, oral dosage forms take the lion’s share of approvals, followed by injectables and topicals
With 445 approvals, oral dosage forms held about 60 per cent of ANDA approvals granted in 2022, followed by injectables with 206 and topicals with 40 approvals. Within the oral dosage forms, 69 are extended-release/delayed-release formulations and 78 approvals for liquid formulations (including powder/granules for solution/suspension). Separately, one buccal film (Buprenorphine) and three chewable tablets also got approval (two for Lanthanum carbonate and one for Meclizine) of which two were for Cipla. Two sublingual tablets (one for Nitroglycerine and one for Fentanyl) were also approved but both have been stated as discontinued. One chewing gum (Fertin) and one lozenge (Aurobindo) for Nicotine Polacrilexalso got approval this year. Diatrizoate meglumine and Diatrizoate sodium oral/rectal liquid for contrast imaging is one of the most notable oral liquid approvals this year. Cetrorelix, succinylcholine chloride PFS, ganirelix and liposomal amphotericin B are some of the notable injectable product approvals. Approval of Breyna metered dose inhalation product of Viatris (the generic equivalent of Symbicort) is arguably the most notable complex product among all approvals this year. Methylphenidate extended-release transdermal film (Daytrana generic) is another one worth mentioning.
Notably, 69 per cent of approvals received by Indian companies were for oral formulations and a little less than 20 per cent for injectables. On the other hand, Chinese companies’ approval basket was represented by 69 per cent injectable products and 26 per cent oral formulations. The preponderance of injectable product approvals for Chinese players could be stemming from the synergies they may desire to leverage in the domestic market based on US ANDA-approved products.
First-time generics and CGT approvals: Indian companies and injectable formulations dominate
A total of 106 approvals are classified as first-time-generic approvals in 2022 and 63 approvals were granted through the Competitive Generic Therapy (CGT) route. 42 per cent of first-time-generic approvals and 38 per cent of CGT approvals were garnered by Indian companies. US-based companies received about 50 per cent of all CGT approvals and 21 per cent of first-time-generic approvals. Looking at the formulations spread, injectables dominated with 48 per cent of first-time approvals and 36 per cent of CGT approvals. Pemetrexed with 14 approvals, lacosamide tablets with eight approvals (of a total 11 this year) and Bortezomib with eight approvals (of a total 17 this year) listed as first-time-generic approval formed a significant proportion of multiple ANDAs getting first-time-generic designation for the same product. Some of the first-time-generic approvals were also for products with innovator brands still under patent protection such as dapagliflozin, empagliflozin and metformin, brivaracetam, sofosbuvir etc.; the status of many such ANDAs is expectedly stated as discontinued. Teva and Apotex with eight approvals each followed by Zydus and Fresenius with seven approvals each lead the table for first-time generic approvals. Amneal with six approvals, Zydus with five and DRL with four approvals gained are the leading players for the number of ANDA approvals through the CGT route. 30 ANDAs were also granted 180-day CGT exclusivity of which five had the exclusivity relinquished or forfeited. Since the FDA started the CGT initiative, about 185 ANDAs have been approved through this route and there are still about 500 innovator NDAs listed for products that are off-patent, off-exclusivity but without an approved generic alternative; these represent a potential opportunity for 180-day exclusivity. However, many of these being only small opportunities, selective filing and approvals are likely to continue in this space.
Discontinuation trend is maintained at the same pace
In line with our earlier analysis, over 11 per cent (86 of 742) ANDAs approved this year are already listed as discontinued, driven by the FDA guidance to notify significant disruption in availability or permanent discontinuation. This also includes nine ANDAs approved through the CGT route. About 18 per cent of ANDAs approved in 2021 and a similar proportion of ANDAs approved in 2020 are now listed as discontinued. If 18 per cent of this year’s ANDAs are also discontinued by next year, it would represent approximately $32 million of sunk cost across all companies (estimated at the current rate of ANDA filing fee and disregarding apportioned program fee, development costs and cost incurred on ANDAs that do not return a positive ROI). While some of these products await the loss of exclusivity of the innovator brand for commercialisation, most companies are invariably always deliberating strategies to minimise loss arising from such real discontinuations, so it will be interesting to see if we witness any stemming of this trend in the years to come.
10 of the top 15 companies are from India
Zydus with 36 approvals topped the overall list of companies getting final ANDA approvals in 2022 followed by Hetero (including its affiliate Annora pharma) with 33 and Amneal with 31 approvals. This year Aurobindo has separately listed Eugia Pharma as a distinct entity, seemingly as the non-oral ANDAs holding company of the group but not listed as an affiliate by the FDA, which it was till last year. If both these entities are viewed together, a total of 44 approvals have been received by the group this year, which would take it to the top of the table if listed together.
Nanjing King-friend and Fosun (Gland Pharma) are the leading Chinese parent companies with 15 and 14 approvals respectively, which are mostly injectables.
Leading companies by number of ANDA approvals in 2021
Among the top 15, Apotex and Teva have the highest number of first-time generic approvals (eight each) followed by Zydus with seven.
A total of 171 companies globally and 47 Indian companies were among those receiving at least one ANDA approval this year. The top 15 companies received 44 per cent of overall ANDA approvals in 2022, while the top 15 Indian companies received 76 per cent of approvals obtained by all Indian players.
Optimus Pharma (one ANDA – Aminocaproic acid tablets) is the only Indian company making an appearance in the approval list for the first time.
Biosimilars
In 2022, seven biosimilars were also approved, taking the total number of biosimilars approved thus far to 40. Additionally, two interchangeable biosimilar products were also approved meet additional requirements and may be substituted for the reference product at the pharmacy without the intervention of a prescriber. The seven biosimilars approved are bevacizumab (2), pegfilgrastim (2), ranibizumab (1), adalimumab and filgrastim. Fresenius Kabi (2 biosimilars) and Amneal (1 biosimilar) are the only traditional generics players with biosimilar approvals this year. Overall, Pfizer (along with Hospira) with eight biosimilars, Viatris (4), Sandoz (4), Fresenius Kabi (2) and Amneal (1) are the only traditional generics players with approved biosimilars, accounting for about 50 per cent of all biosimilars. Indian companies have established their unequivocal dominance in the traditional generics space but are yet to show their presence in biosimilar approvals, except Biocon with its partnered/acquired programs with Viatris.
Conclusion
Significant filing costs of almost a quarter million dollars per ANDA, increasing program fees and continuing pricing pressure with increasing competition have not dampened the interest in participating in the US generics space, especially for Indian players. Companies have not only maintained the momentum but also accelerated filings, even during the ongoing waves of the COVID-19 pandemic, resulting in a higher number of ANDA approvals this year across all dosage forms, competition levels, and product complexity including drug-device combination products. We may see a higher number of approvals through the CGT route in the future as the list of open opportunities gets expanded and companies gain experience. One important trend that generics players are mindful of is the type of new molecular entities getting approved these days, with 54 per cent of those approved in 2022 targeting orphan diseases (meaning much smaller volumes) and a significant proportion being biologics. As we start seeing more interchangeable biosimilars, the interest in that area is definitely increasing but given the enormously larger outlay required for those products, only a handful of traditional generics players are currently planning to foray into that area.
(If you are interested in getting the consolidated dataset used for this analysis in MS-Excel, you may contact the author at meenugrover14@gmail.com)