CGRP (Akela Pharma)

Photo by Flickr user Jernej Furman When it comes to medicine, catering to convenience and patient preference can have life-changing results. Ease of use can influence treatment pathways, long-term adherence, and ultimately clinical outcomes. As patient preference drives clinical adoption, it can also have lasting impact on the market itself. A prime example of this influence was demonstrated last summer, when Johnson & Johnson announced that in just two years’ time, more than 80% of U.S. and European sales for its blockbuster Darzalex for multiple myeloma had shifted from its original IV form to subcutaneous injections. Darzalex was the first anti-CD38 monoclonal antibody approved by the U.S. Food and Drug Administration (FDA) back in 2015. It was so effective that by 2019, it surpassed $2 billion in sales and moved into first-line treatment regimens. However, the IV formulation of Darzalex is extremely burdensome. More than half of all patients experience an infusion reaction, and regimens to reduce these incidents mean extremely slow dosing – up to 8 hours for the first dose, and 4 hours for subsequent doses every 2-4 weeks. In 2020, the second anti-CD38 hit the market – Sanofi’s Sarclisa, which requires half the infusion time of Darzalex. To keep up with the competition, J&J developed the subcutaneous injectable, Darzalex Faspro, which was approved shortly after Sanofi’s drug. The subcutaneous version significantly cut treatment time down from hours to just under five minutes. Darzalex Faspro also cut administration-related reactions by more than half. On top of improving the quality of life for its patients, the introduction of subcutaneous administration increased Darzalex sales by 112%. The Darzalex story is just one of several recent examples highlighting the immense power of patient preference to drive changes in the biopharmaceutical marketplace. In recent years, improving the route of administration for biologics has repeatedly reshaped markets that had been dominated by injected or infused therapies. The logical and final conclusion of this progression is, of course, to convert these drugs into pills. The appeal of pills over needles is no surprise. Needle aversion can lead to missed or delayed treatments and preventive care, causing worse health outcomes. In a 2018 study looking at the influenza vaccine, 16% of adult patients – including 27% of hospital employees and 18% of workers at long-term care facilities – declined to get the vaccination due to needle fear. In line with those findings, the Centers for Disease Control and Prevention estimates that 1 in 10 people may delay Covid-19 vaccines for the same reason. The problem of patient adherence reaches far beyond the fear of a one-time injection. Our recent survey of more than 500 patients and more than 100 physicians and conducted by an independent third party shows the true scope of the issue: more than one-third of patients surveyed who have to give themselves injections for chronic conditions said they skip doses frequently. In a separate survey we did, the independent third party reported the strikingly apparent preference that patients have for an oral route of drug delivery. The survey found that among patients who take an injectable medication as infrequently as twice a year (Prolia), 76% would rather take a pill every day than continue on their current, infrequent injection treatment regimen. There have already been a few examples of drugs being converted to an oral form that show catering to patient preference can have a big impact on the market. In 2017, Novo Nordisk’s Ozempic (semaglutide) was approved as a once-weekly subcutaneous injection for glycemic control in adults with type 2 diabetes. Two years later, Novo Nordisk introduced Rybelsus, an oral formulation of semaglutide for daily administration. With a more convenient route of administration, revenue from semaglutide for the treatment of diabetes increased 105% in just one year. One limitation of the Rybelsus oral technology is that it requires delivery of 100-200 times higher dose per week compared to the subcutaneous formulation (98 mg weekly compared to 1mg or 0.5mg weekly, respectively) – a staggering increase that is needed due to the low absorption rate of Rybelsus via oral administration, with a bioavailability between 0.4%-1%. This significantly increases the cost of goods and can potentially strain the supply chain, an issue exacerbated by the explosion of on- and off-label use of semaglutide for weight loss. Ubrelvy is another evident example of patient preference driving market dynamics and an increase in sales. AbbVie’s Ubrelvy was the first oral CGRP antagonist for the treatment of migraines to hit the market in 2019. Revenues from Ubrelvy rose quickly and continued to grow through 2021, with an overall increase of 182% in revenue from 2020 to 2021. Meanwhile, sales of Amgen’s Aimovig, an injectable CGRP, dropped by 16% the same year, despite having been first to market. Similarly, Amgen’s Otezla was the first oral therapy approved for plaque psoriasis in 2014, and has since become the most-prescribed drug for the indication. This body of data shows that there is a very strong patient preference for more convenient alternatives, with oral being the preferred modality. These preferences can significantly impact revenue and sales. But oral biotherapeutics have not yet proliferated because it is very difficult to make the treatments effective. In the next part of this series, I’ll discuss why it is so difficult to make oral biologics and the technological breakthroughs that may create a future where there is no longer a need for injectable biologics. Photo by Flickr user Jernej Furman