High-value molecules going off-patent – from an emerging markets perspective

Emerging markets are much more heterogeneous place compared to regulated markets like the US and EU. Regulatory norms, application of intellectual property rights, disease pattern, and market size vary considerably between developing countries.

All this means that market access strategy, portfolio management strategy would be quite different for these markets.

In emerging and for emerging markets

The truth is that there is no way to compare emerging markets with markets like the US. In many emerging markets, pharmaceutical manufacturing is dominated by mid and small-cap companies. These companies primarily specialize in producing off-patent branded generics. Some of these countries have quite a robust local pharmaceutical market like India, Brazil, or Russia.

In emerging markets, even the scope of intellectual property rights varies. For example, 46 least developed countries simply qualify for drug patents waiver. Some of these countries, like Bangladesh, have a healthy pharma market and local production.

To complicate things further, many countries like India or Russia may provide drug patent waivers for certain life-saving drugs on humanitarian grounds. Just take the example of Remdesivir. In 2020, the Russian supreme court backed a local manufacturer granting it the right to produce the patented drug.

Biologics aren't as prominent in emerging markets

It is true that as per all the projections, biologics will continue to gain traction. Biological pharma products are going to revolutionize the way diseases are treated. However, in most emerging markets, small molecules will continue to dominate in the foreseeable future. For example, even in nations like China, less than 10% of patients with colorectal cancer are treated with biologics compared to 55% in the US.

Further, there are regulatory challenges in the field, as countries are still identifying a pathway for biosimilars.

Additionally, there is also a difference between the disease pattern between developed markets and emerging markets. All these factors, along with the most vital factor, which is the country's financial capabilities, it appears that small molecules would continue to remain considerably relevant in emerging markets.

Despite all the challenges and ambiguities, considerable growth is expected in emerging markets. Therapeutic areas like diabetes, oncology, anti-infectives, cardiovascular, and nervous system would be the growth drivers.

Below are some of the molecules that have good perspectives in emerging markets. Fortunately, these molecules are either already off-patent in some markets or losing their protection in the next few years:

·        Rivaroxaban (Xarelto): Belongs to a new class of blood thinners that are far safer than warfarin. It is mainly indicated for the prevention of deep vein thrombosis and pulmonary emboli. It is also prescribed to prevent blood clots in those diagnosed with atrial fibrillation or after specific surgical procedures. It has a global market of above 1 billion USD. Still, more importantly, experts estimate that it has a total scope of 6 billion USD.

The only thing to watch out for when going forward with this particular molecule is the country's prescription habits. In some countries, its sister molecule apixaban is more successful.

·        Apixaban (Eliquis): This molecule has similar indications to rivaroxaban and is also indicated to prevent blood clots. However, it is generally regarded as even safer than rivaroxaban, with an even lesser risk of major bleeding. In some of the emerging markets, it has a much greater share than rivaroxaban. This molecule is already 9 billion USD strong globally.

·        Canagliflozin (Invokana): This is a second-line treatment of diabetes. It is the first of the SGLT2 inhibitors to be approved in the US. These drugs work by removing glucose via urine. It is among the potent SGLT2. It's a blockbuster. However, one should be cautious, as the FDA has issued few warnings regarding this drug, like an increased kidney injury and a greater risk of amputation.

·        Dapagliflozin (Farxiga):  Another potent second-line drug for managing diabetes, belonging to SGLT2 inhibitors. Thus, quite like canagliflozin, it works by inhibiting glucose transportation in the kidneys. The good news is that it appears to have an excellent safety profile. Although, kidney health should still be assessed before prescribing it.

However, a piece of bigger news makes this molecule one of the most perspective antidiabetic drugs. It is the first antidiabetic drug approved for heart failure, with or without diabetes.

This new approval by US FDA in 2020 may considerably increase the scope of the molecule. Further, this molecule is good to combine with metformin (Xigduo), further expanding the scope of the molecule.

·        Sitagliptin (Januvia): it is among the most successful second-line drugs to manage diabetes. A DPP-4 inhibitor that boosts insulin production and suppresses glucagon production. Despite reports of some rare side effects, it remains one of the safest antidiabetic medications. It is among the most prescribed drugs for diabetes, usually prescribed along with metformin.

·        Etoricoxib (Arcoxia): COX-2 inhibitors have a long but patchy history. COX-2 inhibitors are generally regarded as safer than other NSAIDs to manage chronic pains like those in osteoarthritis. In addition, they are regarded as a better and safer fit for prolonged use. Many COX-2 inhibitors were introduced in the last few decades with great promises. However, most failed to deliver on their promise of better safety on prolonged use, with post-marketing data showing some severe side effects. However, it seems that researchers have finally found the right COX-2 inhibitor in the form of Etoricoxib. It is already a significant player in many emerging markets. For example, in 2020, two of the top ten launches in Russia were of Etoricoxib brands.

·        Ta-pen-ta-dol (Nu-cyn-ta): A centrally acting opioid analgesic for moderate to severe pains. It is pretty similar to tra-ma-dol but usually has a higher efficacy. It has a higher affinity for mu-opioid receptors, and unlike tra-ma-dol, does not appear to affect 5HT reuptake.

·        Lacosamide (Vimpat): An anti-epileptic drug with a market greater than 1 billion USD and posed to grow, is already creating huge interest in generic manufacturers. It may also be used for neuropathic pains. Although it does not appear to have greater efficacy than older anti-epileptic drugs, it seems to have a much better safety profile.

It may be of particular interest to emerging markets because of its widespread off-label use to manage depression, headaches, migraines, panic disorder, tinnitus, and restless leg syndrome.

·        Remdesivir (Veklury): a small molecule, broad-spectrum anti-viral agent. Originally developed to treat hepatitis C, it gained sudden interest due to the COVID-19 pandemic. Although its patent would expire much later, but legal and regulatory authorities of many countries have made an exception, thus opening the scope for producers of generic drugs. In addition, more than 50 countries have given it emergency approval for use against COVID-19. And numerous countries have approved the sales of remdesivir generics on humanitarian grounds.

·        Cinacalcet (Sensipar): It is the first in a class of so-called calcimimetic compounds. It acts by mimicking the action of calcium in tissues. It is suitable for primary and secondary hyperparathyroidism and parathyroid carcinoma. It has a global market of greater than 1.7 billion USD and has an excellent growth rate of 143%.

The above list is not comprehensive. Nonetheless, these are some of the most perspective small molecules going off-patent. Additionally, this list does not include oncological drugs or biosimilars, as they pose a specific regulatory challenge for many small-molecule producers in emerging markets.

References:

1.      https://www.reuters.com/article/us-health-coronavirus-gilead-sciences-ex-idUSKBN22I1GP

2.      https://www.rferl.org/a/russia-remdesivir-patent-covid-supreme-court-gilead/31277004.html

3.      https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/whats-next-for-biosimilars-in-emerging-markets

4.      https://themedicinemaker.com/manufacture/why-small-molecules-are-still-a-big-deal

5.      https://www.mckinsey.com/industries/pharmaceuticals-and-medical-products/our-insights/whats-next-for-pharma-in-emerging-markets

6.      https://www.pwc.ru/ru/pharmaceutical/publications/assets/Strategyand_Pharma-Emerging-Markets-2.0.pdf

7.      https://www.marketwatch.com/press-release/rivaroxaban-market-size-2021-with-cagr-of-82-top-growth-companies-bayer-jj-and-end-user-swot-analysis-in-industry-2026-2021-06-06#:~:text=The%20global%20Rivaroxaban%20market%20is,8.2%25%20during%202021%2D2026.

8.      https://www.fiercepharma.com/special-report/top-20-drugs-by-2020-sales-eliquis

9.      https://www.endocrineweb.com/news/diabetes/57572-fda-orders-stronger-warning-about-canagliflozin-invokana-amputation-risk

10.   https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-type-heart-failure

11.   https://www.ema.europa.eu/en/documents/product-information/xigduo-epar-product-information_en.pdf

12.   https://www.echemi.com/cms/210254.html

About the Author:

Dr. Preet Pal S.B.

Dr. Preet Pal S.B. is a physician (M.D. Medicine, Kazakh National Medical University) specializing in diabetes (Fellowship in diabetes), a lifetime member of the Indian Medical Association. Dr. Preet has vast business development experience in the ex-soviet republics/CIS region (Ukraine, Kazakhstan, Uzbekistan, Russia, Kyrgyzstan, Azerbaijan, and so on). Dr. Preet is a  multilinguistic. He has held senior management posts in various healthcare/pharmaceutical companies like SEARLE – central Asia (now a subdivision of Pfizer), Shreya life sciences, AGIO pharma, Indian Immunological Limited (Human and veterinary biologicals). 
Dr. Preet is also a prolific writer and loves sharing my experiences. He firmly believe that an approach towards emerging markets differs considerably from developed markets. The bigger part of the global population resides in emerging markets. Yet, regretfully, most market reports remain focused on the developed markets. Even if they focus on emerging markets, they often use insights gained from developed markets.