For a drug that is predicted to generate $1.7bn in sales and royalties by 2014 the diabetes drug Onglyza has slipped into the market with barely a ripple or movement in the share prices of partners AstraZeneca (NYSE:AZN) and Bristol-Myers Squibb (NYSE:BMY).
By late afternoon in London yesterday, Astra shares, which had risen 20% in the last three months, were flat at £27.91½. BMY shares were also stagnant in early New York trade at $21.80. This seeming lack of excitement by the market for the drug which is forecast to be the third and second biggest growth driver at each company respectively, is due to the fact that Friday’s thumbs up from the US regulator was widely expected and therefore largely in the shares prices of both groups.
The writing on the wall for approval started in April after an FDA advisory committee voted 10-2 to approve the drug, agreeing that the level of cardiovascular risk was acceptable when compared to other marketed products in the space (FDA panel review points to DPP-IV success in diabetes market, April 3, 2009).
Notwithstanding the hiccup of Onglyza’s PDUFA date being moved from the end of April to the end of July, (AstraZeneca and Bristol-Myers Squibb face short delay to Onglyza approval , April 23, 2009), additional confidence it would make to market was supplied by European regulators who, recommended approval for the drug on June 25.
However, despite these positive omens the ultra cautious in the market had predicted that the FDA might want to wait for the results of trials showing the drugs effects on the skin of patients with renal impairment before granting approval.
The worry about renal impairment goes back to pre-clinical studies that had shown Onglyza had the ability to cause skin lesions in monkeys, a similar side effect that prevented the US approval of Novartis’ (NYSE:NVS) Galvus.
What appears to have prevented Astra and BMS from having to wait for the renal studies were the much higher doses of Onglyza that had to be used for lesions to appear, 60 times the maximum recommended dose, compared with just 6 to 8 times the maximum dose for Galvus.
US approval of Onglyza leaves it as the second DPP-IV inhibitor on the market in the US, following the approval of Januvia in 2006, which managed to notch up impressive sales of $1.4bn last year.
DPP-IV inhibitors work by affecting the action of natural hormones in the body called incretins. Incretins decrease elevated blood sugar levels by increasing the body's utilisation of sugar, mainly through increasing insulin production in the pancreas and decreasing glucagon secretion.
Despite being second to market many are expecting that Onglyza will be able to capture a fair share. UBS believes that Onglyza’s smaller pill size and its once-daily combination with metformin, instead of twice-daily for Janumet, Merck & Co’s (NYSE:MRK) sitagliptin and metformin combination pill, will help to drive sales. Astra also announced today that it would be pricing Onglyza at the same level as Januvia setting the two up for a battle for market share that could slow the impressive growth profile of Januvia, which is likely to retain its first mover advantage.
The approval of Onglyza should also give the handful of late-stage DPP-IV inhibitors queuing up to get a slice of the highly lucrative diabetes market some hope (see table). However, the most advanced, Takeda’s (OTCPK:TKPHF) alogliptin, is staring down the barrel of a very long wait for approval following its failure to provide the FDA with enough clinical data to allow it to adequately assess the cardiovascular safety of the drug, which earned it a complete response letter in June (Alogliptin disappointment continues for Takeda, June 29, 2009).
Ono Pharmaceuticals (OTC:OPHLF) has filed its drug, Glactiv, in Japan and could get approval by next year, but it is not clear if the group has a strategy for the US. PHX1149, a drug being developed by Forest Laboratories and Phenomix, is not expected to complete its latest set of phase III trials until April 2010, meaning that it is unlikely to be on the market until about 2011.
All of these drugs face a potentially longer and tougher time to approval in the US given that they will have to go through the FDA’s new stringent marketing process for diabetes drugs that requires two years of cardiovascular safety data. This will leave Januvia and now Oglyza to enjoy a market that some analysts estimate will be worth $7bn by 2015, for some time to come.