2023 Patent Apocalypse, Generics Get a Boost? Please check out this Top 10 patent cliff

FiercePharma rounded up the TOP10 biggest patent cliffs of 2023. Among them, MNC names such as AbbVie, Takeda, Johnson & Johnson, Roche and Sanofi are on the list.

/ 01 / Humira(Adamumab)

Humira, the world's best-selling non-coronavirus drug, has generated more than $200 billion for AbbVie over the past two decades. In 2022, Humira's annual sales reached $21.237 billion, up 2.6% from the previous year.

Currently, Humira's first and only biosimilar competitor in the United States is Amgen's Amjevita, which officially launched at the end of January.

Abbvie is not going to let Humira, its immunology champion, go down without a fight, even though many biosimilars are gearing up.

In the face of that competition, AbbVie says it still expects to see a return to sales growth in 2023 with its twin drugs Rinvoq and Skyrizi. Combined, the two drugs are estimated to surpass Humira's peak sales of $20 billion by 2027.

Amgen's Amjevita will have its own market in a matter of months, thanks to a 2017 settlement with AbbVie. Although seven more biosimilars are expected to hit the market from July.

However, it remains to be seen how this highly competitive market will evolve once all bioanalogues hit the market.

/ 02 / Stelara(ulsinumab)

Stelara, J&J's top cash cow, is in an odd position when it comes to patent life and encroachment on bioanalogues. Although the immunological drug's patent expires in 2023, the pipeline for biosimilars is empty.

For all of 2022, Stelara raked in impressive sales of $9.72 billion worldwide, with $6.39 billion of that coming from the U.S.

Given this open playing field, J&J Chief Financial Officer JoeWolk said on a recent call with investors that Stelara is expected to continue to grow in the U.S. until the drug loses exclusiveness in September 2023.

In the U.S., a handful of biosimilar competitors that could pose a threat to Stelara have yet to win regulatory approval, providing J&J with a buffer period to secure revenue.

milvexian, a blood clot candidate with Bristol-Myers Squibb, and a combination of amivantamab and lazertinib for non-small cell lung cancer are J&J's battle weapons in this patent crisis. J&J also has high hopes for the potential value of its collaboration with Legend on a CAR-T treatment for multiple myeloma, known as Carvykti, JenniferTaubert, executive vice president and global chairman of J&J, said on the same earnings call.

Other challengers in the pipeline for Stelara's bioanalog are BioconBiologics, Alvotech and Amgen.

/ 03 / Vyvanse

Vyvanse, one of Takeda's biggest sellers and the third-biggest seller among Japanese drugmakers, is used to treat attention deficit/hyperactivity disorder. The drug generated $2.53 billion (335 billion yen) in U.S. revenue last year, a solid increase from 2021. Patent protection for the drug expires in the United States in August, and extends to February 2028 and March 2029 in some countries.

On a conference call with investors last May, Takeda executives said sales would take some hit in 2023 from falling off the patent cliff, but additional revenue was expected from ulcerative colitis and Crohn's disease drug Entyvio, hereditary angioedema drug Takhzyro and other new drugs on the market. To make up for the drop in sales from the expiration of Vyvanse's patent.

Takeda has also taken pains to protect Vyvanse's patents, filing at least four patent lawsuits, according to reports. Notably, Takeda bought Shire for $62 billion in 2019, giving it an interest in Vyvanse.

Currently, biosimilar competitors waiting at the entrance of the market include Teva Pharmaceutical, Amneal, and Novartis.

/ 4 / Aubagio

Aubagio, which is produced by Sanofi and is one of its blockbuster products, reported global sales of 2.03 billion euros in 2022, down 4.3% from 2021. Of that, $1.42 billion came from the United States, Sanofi's fourth ace in the hole last year after Dupixent, flu vaccine and Lantus.

The Dupixent development is well underway, but Sanofi isn't taking Aubagio's U.S. patent cliff lying down.

Generic versions of Aubagio will enter the American market this year. Back in 2017, Sanofi reached a settlement with 20 generic drug developers that allowed it to launch a generic version of Aubagio after its U.S. patent protection expired. In Europe, Aubagio is expected to face generic challenges in the fourth quarter.

Compared with Biogen's now-off-patent Tecfidera and its successor Vumerity, both of which are administered twice daily, Aubagio has the convenience of a once-daily pill.

But the multiple sclerosis market has become increasingly crowded, with a growing number of entrants to once-daily oral drugs, including Novartis Gilenya and the new Mayzent, Bristol-Myers Squibb's Zeposia and Johnson & Johnson's Ponvory.

/ 05 / Actemra(tolumab)

Actemra is an IL-6 inhibitor from Roche used in the treatment of rheumatoid arthritis, giant cell arteritis, juvenile idiopathic arthritis, cytokine release syndrome and other conditions.

After being included in China's COVID-19 treatment guidelines in March 2020, Actemra received FDA emergency use authorization in June 2021 for the treatment of certain severe COVID-19 patients. Late last year, Actemra won full FDA approval for intravenous administration of the drug to treat hospitalized adult COVID-19 patients receiving additional care.

The COVID-19 pandemic is cashing in on Roche just as patent protection is about to expire. In 2021, Actemra's sales reached 3.56 billion Swiss francs, an increase of 27% from 2020. Actemra's sales in 2020 were up 32% from 2019. However, Acemtra's sales fell 22 percent in 2022 due to a drop in demand from inpatients due to COVID-19.

Roche said it expects the first biosimilars of Actemra/RoActemra to be available in the United States and the European Union in the second half of 2023, based on publicly available information from competitors including Celltrion and Biogen.

/ 6 / Xyrem(sodium oxybutyrate)

Xyrem is a narcolepsy drug made by Jazz, and accounted for 28% of Jazz's 2022 sales, or $1.02 billion. While Xyrem isn't quite among the top drugs in this report in terms of total sales, it's a true treasure for Jazz.

Now, however, competition for the generic version of Xyrem has begun.

On the first business day of this year, Hikma launched a licensed generic version under an exclusive agreement it signed with Jazz back in 2017. The generic version of Hikma will have 180 days of market exclusivity. Jazz also signed a patent settlement agreement with Amneal in 2018, allowing Amneal to launch a limited number of generic versions on July 1.

Jazz has responded to the patent cliff with the introduction of cationic hydroxybutyrate therapy Xywav.

And when it comes to diversifying its operations, Jazz is picking up the pace, acquiring GW Pharmaceuticals for $7.2 billion in 2021. Acquired full rights to Epidiolex, a cannabinol-based drug used to treat certain rare forms of epilepsy, and saw sales increase 12 percent to $736 million in 2022.

/ 07 / Symbicort(Budesonide/Formoterol)

Symbicort is Astrazeneca's respiratory star product and has been a reliable revenue contributor for many years. But its exclusive rights in the United States are likely to end this year.

Symbicort, a combination of the corticosteroid budesonide and the long-acting beta-agonist (LABA) formoterol, was first approved by the FDA to treat asthma in 2006 and was approved in 2009 for chronic obstructive pulmonary disease (COPD).

Symbicort generated $2.538 billion in revenue worldwide in 2022, down 2% year-over-year on a constant currency basis. Sales in the United States were $973 million, down 9% from 2021 and still Astrazeneca's top selling product in the respiratory segment, despite the decline in revenue.

Astrazeneca, meanwhile, is in a long-running court battle with Viatris and KindevaDrugDelivery over a patent dispute with Symbicort. In March 2022, Kindeva's generic version of Symbicort won final FDA approval under the trade name Breyna. But Astrazeneca's patent litigation, Viatris has not yet launched the generic version, but Viatris is undoubtedly Astrazeneca's closest competitor.

/ 08 / Lexiscan

Lexiscan, a cardiovascular contrast agent originally developed by CVTherapeutics, was approved for marketing by the FDA in April 2008. According to Astellas, the product will generate $720 million in U.S. sales in 2022.

Lexiscan has a five-year patent war behind it.

Lexiscan was originally owned by CVTherapeutics, which was approved by the FDA in 2008. In 2009, Gilead acquired CVTherapeutics for $1.4 billion, and Gilead later licensed it to Astellas.

To avoid generic competition, Pfizer's Hospira generics unit filed a generic application for its version of Lexiscan.

Astellas and Gilead sued Curia, which makes the active pharmaceutical ingredient for the product, and lost.

/ 09 / Gattex

Gattex is a glucagon-like peptide-2 (GLP-2) analogue, a naturally occurring hormone that reduces gastric emptyand secretion, used in the treatment of short bowel syndrome (SBS) in adults. The drug had sales of about $540 million (74 billion yen) in the United States in 2022.

In addition to ADHD drug Vyvanse, Takeda's short-bowel syndrome drug Gattex will also face the first biosimilar challenge from March.

Takeda's annual report noted that Gattex could be launched after March 2023 under a settlement agreement with an unnamed bioanalogue manufacturer.

However, according to a recent search of the FDA's approval database, no biosimilar drug manufacturers have received regulatory approval. It is unclear whether Endo, a unit of Johnson & Johnson, will be able to launch its Gattex biosimilar, as the company filed for bankruptcy protection in August.

In addition, Sealand's Glepalutide, a long-acting GLP-2 analogue being investigated for the treatment of short bowel syndrome, has been designated an orphan drug by the FDA and is currently in Phase 3 trials.

 /10 / TrokendiXR(topiramate)

2023 is certainly going to be a tough year for SupernusPharmaceuticals, as its longtime bestseller TrokendiXR will face its first U.S. generic competition. For now, Supernus will have to rely on new growth forces to withstand the onslaught of its star products falling off the patent cliff.

Trokendi has enjoyed 10 years of market exclusivity since its initial FDA approval in 2013. The drug, which is approved to treat certain seizures and prevent migraines, has been the apple of Supernus' eye for years.

A family is happy and a family is sad. The countdown to Trokendi's patent dividend has begun, signaling time for Zydus and other generic drugmakers to grab a piece of the market. Zydus launched a generic version of TrokendiXR on Jan. 18. Back in 2017, Zydu reached a settlement agreement with Supernus that allowed the generic version of Zydus to enter the market at the beginning of the year.

Meanwhile, Supernus braced itself for the loss of exclusivity. Sensing a looming cliff, Supernus paid $400 million for AdamasPharmaceuticals in 2021, taking ownership of Gocovri and OsmolexER.