* Imminent launch of Phase III fostamatinib clinical trials
* Astra gained experience after failure of in-house products
* Drug licensed from Rigel seen as key late-stage asset
* Chasing Pfizer in race for rheumatoid arthritis pill
By Ben Hirschler
LONDON, Sept 28 (Reuters) - AstraZeneca (AZN.L) is set to start costly final-stage trials of a new pill for rheumatoid arthritis, ramping up investment in a programme that highlights its new-found pragmatism towards drug development.
The imminent launch of Phase III studies with fostamatinib, just six months after a licensing deal for the product was finalised with Rigel Pharmaceuticals (RIGL.O), underlines the group's readiness to "externalise" the hunt for new drugs.
AstraZeneca is chasing rival Pfizer (PFE.N) in a race to develop a convenient oral alternative to costly anti-TNF injections, which have led the field for the past decade.
The Anglo-Swedish company, which badly needs new products to bolster its late-stage pipeline, had originally hoped to develop an oral arthritis drug in house -- but that project hit a wall in 2009 when two experimental products failed to show efficacy.
In a quick strategic turn, however, AstraZeneca jumped horses and signed up Rigel's product instead.
"It illustrates a departure for AstraZeneca. At the same time as we were progressing with our own two compounds in Phase IIb, we were also looking at the competitive opposition," said Ricky Bache, head of the fostamatinib global product team.
"Within two weeks of us regrettably finding we had a negative result with our compounds, we were already talking to Rigel ... We're pretty pleased with how fast we moved," he said in an interview.
If all goes well, fostamatinib, also known as R788, will be submitted for U.S. and European regulatory approval in 2013 and could be launched in its first markets in 2014.
Rigel got a handsome $100 million upfront payment from AstraZeneca back in February and is entitled to up to $1.25 billion, if the drug is a success. [ID:nSGE61F054]
But speed, as well as cash, was also a big consideration when Rigel picked its partner, and the fact that AstraZeneca had already done a lot of groundwork for its failed compounds meant it could move faster than rivals in starting late-stage trials.
PIPELINE PRIORITY
The move into Phase III will cost hundreds of millions of dollars, underscoring the big bet being placed on fostamatinib.
"It is an expensive area to develop drugs in by nature of the regulatory requirements, but it is a key opportunity for us," said Lisa Anson, vice president for AstraZeneca's emerging brands. "It is certainly one of our top Phase III priorities."
AstraZeneca needs to find new winners to offset expiring patents on some of its best-selling medicines, such as heartburn treatment Nexium and Seroquel for schizophrenia.
Its recent product development news has been mixed, with heart drug Brilinta recommended for approval in Europe last week but its cancer drug pipeline suffering another setback on Monday. [ID:nLDE68N188]
Fostamatinib, a so-called spleen tyrosine kinase (Syk) inhibitor, is viewed as a potential blockbuster that could help transform pipeline prospects, although it is by no means perfect. Mid-stage clinical trials found it could increase blood pressure levels and one of three Phase II studies also showed a worrying lack of effectiveness.
Despite this, AstraZeneca is confident. Bache said the blood pressure issue was manageable, and the one failed trial appeared to be due to technical issues with study design [IMO R788 failed in the referenced Phase 2b trial because the patient population had also failed existing biologics, so to me it's not too surprising that a drug fashioned to work similar to existing biologics, but as a pill, would fail to show efficacy in a patient population where the biologics also failed].
Given as a once- or twice-daily pill, the new drug is a rival for current rheumatoid arthritis injections that include expensive biotech medicines such as Humira from Abbott Laboratories (ABT.N) and Amgen's (AMGN.O) Enbrel.
But it also faces competition from another new class of oral medicines, led by Pfizer's (PFE.N) JAK-3 inhibitor CP-690,550, which has been in Phase III development for more than a year and is likely to be first to market among the new wave of pills.
One differentiating factor with fostamatinib could be its faster onset of action, which is important in rheumatoid arthritis since it means earlier bone protection.
Given the variability of response among arthritis patients to different types of drugs, AstraZeneca believes there is unlikely to be a single winner among the new pills.
Within the Syk inhibitor space, Bache estimates fostamatinib is at least two or three years ahead of rivals, which include a Phase I product from unlisted U.S. firm Portola Pharmaceuticals. (Editing by Will Waterman)
[This presentation is from a few months ago but I have RIGL back on my watch list and wanted to catch up on things. There were some notable disclosures from this presentation, as reflected below.]
1. R788 for RA which is now partnered with AZN and in Phase 3 is now generally referred to as FosD. Although the prior post detailing the AZN deal just generally referred to RIGL receiving stepped-up double-digit royalties on FosD sales, the CEO specifically disclosed during this presentation that RIGL will be entitled to royalties on FosD sales that start at 20% in the U.S. and scale up to 35%. This is quite a deal for RIGL, IMO, especially considering the fact that they don't have to spend another dime on the drug's development or the ultimate marketing if the drug makes it to market (i.e., RIGL is not required to co-promote FosD to receive these royalties).
2. Trials for FosD against lupus will follow the start of the Phase 3 for RA and oncology trials will also start in 2011.
3. RIGL believes that FosD may inhibit bone damage in RA patients faster than TNF inhibitors, which would be a big differentiating point in the marketplace.
4. AZN will be testing FosD in 3000 patients in the double-blind pivotals and in double that number of patients in the additional sub-studies, including Phase 3b trials. AZN anticipates a 6,000 - 10,000 patient safety database at the time the FosD NDA submission is approved. This will be the biggest single indication Phase 3 trials that AZN has ever done, including cardiovascular trials.
5. RIGL is partnered with PFE for R343, an inhaled SYK inhibitor that targets asthma. PFE will be presenting Phase 2 results later this year that show that the drug "worked" and will be moving into Phase 2b later this fall. RIGL is entitled to additional milestones on drug development and, ultimately, mid double-digit royalties if the drug makes it to market.
6. RIGL expects to initiate Phase 1 trials for R348, its JAK3 inhibitor, this year targeting transplant rejection. Actual trials testing the drug in transplant rejection patients are targeted for 1Q11. RIGL expects there to be advantages in the transplant rejection population for a drug that is specific for JAK3 as opposed to also hitting JAK2.
7. RIGL expects to commence Phase 1 trials in early 2011 for its PKC theta inhibitor where they are targeting MS. This is a completely novel mechanism and RIGL expects the drug to be an oral once/day small molecule drug. The drug works better than anything they've seen in pre-clinical MS models but these models are not as predictive for drug activity in humans as models used for other diseases.
8. RIGL also is developing ACVR2B for muscle atrophy and R481 (adiponectin for T2DM/muscle metabolism). These drugs will enter the clinic in late 2011 and early 2012. ACVR2B activates fast-twitch muscle fibers and is downstream of the myostatin pathway. R481 is an oral agonist of adiponectin, which is widely applicable in muscle metabolism. R481 is apparently the first oral molecule to trigger this pathway.
Market Data 
Markets 
AI
