17 July 2018

The Rise of Orals

With four oral JAK-i therapies expected to be available to rheumatoid arthritis patients by the end of 2019 we discuss how oral therapies may change therapy choices

For more than 15 years anti-TNF therapies delivered via subcutaneous injection or IV infusion have been the cornerstone therapies for immunological diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ulcerative colitis (UC) and Crohn’s disease (CD). That is until Pfizer and Lilly launched their oral JAK-i therapies in 2016/2017* in RA.

Now there is a rich pipeline of late stage oral therapies expected to launch in immunological indications over the next 5 years. This includes AbbVie’s JAK1 upadacitinib which demonstrated superiority to the company’s own blockbuster standard of care Humira in RA and Gilead Galapagos’ JAK1 filgotinib which is expected to launch in RA 2019 and be the first JAK in CD. In IBD Celgene and Arena Pharmaceuticals are also investigating oral S1P1 modulators; Celgene’s ozanimod is expected to complete Phase 3 trials Q4 2019.

For years in qualitative interviews we frequently heard from patients that they would prefer an oral therapy to injections or infusions. On a practical level this is driven, for example, by the inconvenience of attending infusion appointments, pain of injecting, organising travel around injection times and carrying cold boxes to maintain correct temperature of injection pens or syringes.

But it is on, an often latent, emotional level that patients struggle with their injection and infusion regimens. In the beginning, it can be the fear of the needle and the pain associated with delivering the medication or accidentally hitting a vein. The ‘invasion’ of their disease into their home can also be a significant emotional barrier as biologics must be stored in the fridge and patients require a bright yellow sharps bin for safe disposal. As therapy becomes the ‘norm’, needle-fatigue, where patients feel they can no longer face their medication, is very common amongst those with chronic conditions such as RA or UC.

Oral therapies do offer an alternative path, but they are not without their own practical and emotional hurdles. One of which is the need for daily compliance, which some may see as a greater burden than infrequent injections. For other patients, the process of injecting or attending hospital infusion appointments provides a reassurance that they are correctly taking their medication.  

That said, the developments in the immunology pipeline offer patients and physicians increased choice. Some of this choice is driven by clinical need, but it also provides the option for patients to discuss which route of administration is best suited to their lifestyle. Ultimately, greater choice and engagement in therapy decisions will help to foster patient empowerment and ownership of their therapy regimen.

As oral therapies become more widespread and approved in new indications we look forward to the opportunity to research the impact with patients and physicians.

*Pfizer’s pan-JAK Xeljanz was the first to be approved by FDA in 2012, followed by EU approval in March 2017. Lilly’s JAK1/2 Olumiant was the first approved by EMA in Feb. 2017, whilst the FDA only approved one of the two doses (2mg not the 4mg) in June 2018.