Novartis/Ophthotech eye combo fails in phase 3

Novartis and Ophthotech's pegpleranib has flopped in two phase 3 trials, failing to improve efficacy when added to the Swiss pharma’s Lucentis in neovascular age-related macular degeneration (wet AMD).

Lucentis still has a few more years left on its patents in the US and Europe, but Novartis wants to find new combinations, or successors to the big-selling eye drug.

Pegpleranib is a genetically engineered DNA strand, or aptamer, that through interaction with other targets, strips away cells that wrap around and protect the rogue blood vessels that cause AMD.

Novartis hoped that combining Lucentis with pegpleranib would improve efficacy compared with standard of care – which is Lucentis alone.

But the studies OPH 1002 and OPH 1003, sponsored by Ophthotech did not meet the primary endpoint of superiority for the combination therapy, measured by improvement in performance when reading an eye chart.

After a year, patients in the pegpleranib and Lucentis (ranibizumab) combination treatment group showed a 10.74 letter best corrected visual acuity (BCVA) improvement in study OPH1002, and a 9.91 letter BCVA improvement in study OPH1003.

Patients treated with ranibizumab alone showed a 9.82 letter BCVA improvement in the OPH1002 study and a 10.36 letter BCVA improvement in the OPH1003 study.

In May 2014, Novartis signed a licensing and commercialisation agreement with Ophthotech, and holds the exclusive rights to pegpleranib outside the US. Ophthotech holds the rights to pegpleranib in the US.

But it looks unlikely that Novartis will continue further development of the combination. At the same time, Vasant Narasimhan, Novartis’ chief medical officer, said it was “fully committed” to developing Lucentis as standard of care for diseases of the retina.

Novartis and Ophthotech will continue to analyse the data, and the Swiss pharma has high hopes for RTH258, a next-generation eye drug developed by its Alcon unit.

This year has seen lots of speculation around whether or not Novartis will sell off Alcon, which currently makes a loss. Novartis chairman Joerg Reinhardt confirmed last month that the company will consider a divestment.