The increasing incidence of rheumatoid arthritis caused by ageing Western populations is set to drive demand for drugs that treat both the disease itself and the symptoms, from non-prescription NSAIDs up to complex and expensive biological anti-TNF therapies.
As such, the pipeline of experimental drugs targeting RA is pretty full, with 4 novel compounds in late stage trials, and 51 in phase II (see table below). However, despite the huge success of the anti-TNF class, much hope is being held out for a break though in new oral remedies, and the first truly efficacious drug to reach the market in this segment is likely to be very successful.
The table below shows that oral approaches represent around half the approaches under development, at least in phase II and III. Pfizer is the most advanced with CP-690,550, a JAK-3 inhibitor which entered phase III in February.
|Count of pipeline RA products|
|Phase||Product Count||Route of Admin|
|Total active projects||259|
|Abandoned - Phase III||4|
|Abandoned - Phase II||50|
|Abandoned - Phase I||37|
|Abandoned - Pre-clinical||36|
|Abandoned - Research project||13|
|Abandoned - Unclassified||80|
|Total abandoned projects||220|
Eisai’s iguratimod appears to be a complex molecule described as being anti-TNF, IL-1, IL-6, IL-8 and a COX-2 inhibitor.
Not far behind, however is Rigel’s R788, which is close to announcing the final set of phase IIb data (Event - Rigel looking strong as second data set approaches, July 10, 2009). A partner is being sought, and considering the drug is the only Syk inhibitor in clinical development, could attract some attention. With the majority of the big pharma names already present on the list, any number of parties are likely to be taking a look.
|Rheumatoid Arthritis Market - key pipeline products||WW annual sales ($m)|
|Phase||Product||Generic Name||Company (s)||Pharmacological Class||Route of Admin||Lead Indication Summary||Launch WW||2010||2012||2014|
|Phase III||Arzerra||ofatumumab||GlaxoSmithKline + Genmab||Anti-CD20 MAb||Injection||CLL [Filed]; NHL [Phase III]; RA [Phase III]||-||113||355||624|
|PRO70769 (R1594)||ocrelizumab||Roche + Biogen Idec||Anti-CD20 MAb||Injection||RA [Phase III]; SLE [Phase III]; MS [Phase II]; NHL [Phase II]||Dec-2010||-||223||543|
|CP-690,550||-||Pfizer||Janus kinase-3 (JAK-3) inhibitor||Oral||RA [Phase III]||Dec-2011||-||100||380|
|Kolbet / Careram (T-614)||iguratimod||Eisai + Taisho Toyama Pharmaceutical JV||Anti-TNF, IL-1, IL-6, IL-8 & COX-2 inhibitor||Oral||RA [Phase III]||Dec-2012||-||57||69|
|Phase II||Denosumab (AMG 162)||denosumab||Amgen||Anti-RANKL MAb||Injection||OA [Filed]; Bone repair & regeneration [Filed]; Bone metastases [Filed]; RA [Phase II]||-||411||2,152||3,648|
|Benlysta||belimumab||Human Genome Sciences + GlaxoSmithKline||Anti-B lymphocyte stimulator (BLyS) MAb||Injection||SLE [Phase III]; RA [Phase II]||-||17||69||185|
|Atacicept||atacicept||Merck KGaA + ZymoGenetics||B lymphocyte stimulator (BLyS) & a proliferation-inducing ligand (APRIL) inhibitor||Injection||SLE [Phase III]; RA [Phase II]; MS [Phase II]||-||-||16||33|
|TRU-015||-||Wyeth + Trubion Pharmaceuticals||CD20 inhibitor||Injection||RA [Phase II]||Dec-2013||-||-||20|
|BMS-582949||-||Bristol-Myers Squibb||p38 MAP kinase inhibitor||Oral||Psoriasis [Phase II]; RA [Phase II]||-||-||-||19|
|PH-797804||-||Pfizer||p38 MAP kinase inhibitor||Oral||RA [Phase II]; COAD/COPD [Phase II]; Post-herpetic neuralgia [Phase II]||Dec-2012||-||-||11|
|RhuDex||-||MediGene + Active Biotech||CD80 antagonist||Oral||RA [Phase II]||Dec-2012||-||-||3|
|681323||dilmapimod||GlaxoSmithKline||p38 MAP kinase inhibitor||Oral||COAD/COPD [Phase II]; RA [Phase II]||Dec-2012||-||-||-|
|856553||losmapimod||GlaxoSmithKline||p38 MAP kinase inhibitor||Oral||COAD/COPD [Phase II]; RA [Phase II]||Dec-2012||-||-||-|
|PG-760564||-||Procter & Gamble||p38 MAP kinase inhibitor||Oral||RA [Phase II]||-||-||-||-|
|PS540446||-||Ligand Pharmaceuticals||p38 MAP kinase inhibitor||Oral||Psoriasis [Phase II]; RA [Phase II]; Atherosclerosis [Phase II]||-||-||-||-|
|R406/R788||fostamatinib||Rigel Pharmaceuticals||Syk kinase inhibitor||Oral||RA [Phase II]; Thrombocytopaenia [Phase II]; NHL [Phase II]||Dec-2011||-||-||-|
However, the table below shows that deals for RA have dropped off considerably this year.
|Product Deals for RA Drugs|
|Deal Date||Deal Count|
Only two deals have been struck so far this year, the most recent being Purdue Pharma and Nitec, the former buying European rights to Lodotra, a slow release formulation of prednisone. The other deal was struck by Roche, which licensed Synta Pharmaceuticals’ CRACM inhibitor programme, which is still only a research project, but are orally bioavailable, paying $26m upfront.
This decline in deals could possibly be due to the huge success of the anti-TNF approach, which has deterred development of the competition. Sales of Abbott Laboratories' Humira are seen doubling by 2014 to $9.0bn, when Enbrel, sold by Wyeth and Amgen, is forecast to be a generating $6.5bn. Although it should be remembered these drugs are also sold for other autoimmune diseases such as psoriasis and Crohn's disease.
Of the 259 RA products in development, just 11 are TNF inhibitors. Clearly the focus has shifted elsewhere, and perhaps until these new approaches have demonstrated they can stand up to the TNFs in terms of efficacy, deal levels will not return.
In fact, the R&D landscape is becoming increasingly dominated by p38 MAP kinase inhibitors, which are shaping up to replace the anti-TNFs in terms of R&D dollar spend. GlaxoSmithKline, Bristol-Myers Squibb and Pfizer are currently developing the most advanced of these orally-delivered, p38 MAP kinase inhibitors.
|Leading Classes of active Pipeline RA Drugs|
|Pharmacological Class||Count of products|
|p38 MAP kinase inhibitor||14|
|TNF inhibitors / Anti-TNF MAb||11|
|NF-kB inhibitor / modulator||7|
|CD20 inhibitors / Anti-CD20 MAb||6|
|Janus kinase-3 (JAK-3) inhibitor||5|
|Melanocortin (MC) receptor agonist||4|
|P2X7 ion channel antagonist||4|