I think we’d all agree that 2013 was an exciting year for biotech and pharma drug development. New drug approvals, great late stage clinical trial results and exciting scientific data gave us all a wealth of topics to think about and discuss. There will be much more of this in 2014 and we can expect the excitement to continue. In the middle of all this however sits a big pile of unresolved questions and a plethora of diseases for which new therapies remain few of lacking. I want to pull a few things off that pile and have a look. What follows is a short list of drug development questions in the fields of inflammation, autoimmunity and oncology.
1) Will the use of biologics for Rheumatoid Arthritis (RA) begin to taper?
The blockbuster TNF antagonists Remicade, Enbrel and Humira continue to dominate the market for disease-modifying RA therapies (DMARDs). These drugs, other anti-TNF drugs, Stelara (anti IL-6 antibody), Orencia (CTLA4 fusion protein) and Rituxan (CD20 antibody) have transformed RA patient care to the point that the Rheumatologist’s goal has become disease remission.
Two challenges to the dominance of biologics were brought forward in 2013. One was the hypothesis that “triple therapy” – the use of a combination of the old and cheap chemical drugs methotrexate, sulfasalazine and hydroxchloroquine was just as effective as a TNF antagonist with or without methotrexate. This debate played out at the American College of Rheumatology conference in November. The consensus view that emerged was that triple therapy was effective for patients with mild RA who could tolerate the regimen. The problem is that triple therapy is very unpleasant and compliance can be very poor, especially in younger patients. The debate, while energetic, does not seem to have had an impact on the biologics market in RA.
The second challenge was brought on by the approval of Pfizer’s Jak2 inhibitor, a once-daily oral drug. Orals are considered the holy grail of RA drug development, allowing patients to move off of therapies that require either IV injections (in a health care setting) or subcutaneous injections (in a health care setting or self-administered). All approved biologics for RA are injectable drugs.
As discussed in that earlier post, Xeljanz showed impressive efficacy in RA clinical trials, and as approved by the FDA for use in methotrexate-refractory patients. This second-line label meant that patients did not have to try a biologic first, they could go directly to this nice, convenient once-a-day oral. So what happened?
Not much. Physicians balked at some of the side effects, and payers balked at the cost. The result was that this presumed blockbuster oral drug has posted very poor sales to date. It may be that Xejanz gains traction over time, we’ll have to see, but already we can take away several interesting lessons. One is that physicians have gotten comfortable with biologics, and being an oral drug does not automatically confer advantage. The second, which is really an old lesson, is that drug efficacy is paramount, and new drugs need to offer better efficacy. This is especially true if they are bringing some side-effect baggage along with them.
Is anything else in development that can challenge the established biologics in the near term? I think the short answer is no. Apremilast, Celgene’s PDE4 inhibitor, has trialed well in psoriatic arthritis and psoriasis, but did poorly in RA trials, so poorly that scheduled trials were terminated or withdrawn. Other Jak inhibitors and Syk, BTK and other inhibitors are currently in RA trials, but these are years away from approval. Some, like the Syk inhibitors fostamatinib from Rigel/Astra Zeneca and PRT062607 from Portola/Biogen Idec, have already failed.
Perhaps the next hurdle for the RA biologics will be the launch of biosimilar products, essentially generic versions of the antibody or protein. Thats a topic for another time.
In section 2 we will turn to an autoimmune disease that remains very poorly treated.