Ophthotech’s anti-PDGF med fails late-stage combo tests in wet AMD

Ophthotech has seen its share price decimated after it announced over the weekend that its big hope, and what much of its financing has been centered around in recent years, failed to help wet AMD patients see better when used with Novartis’ blockbuster VEGF med Lucentis (ranibizumab).

In fact, the two phase 3 pivotal trials showed that adding its med Fovista (pegpleranib) with Lucentis failed to be significantly better than using Lucentis alone in more than 1,200 patients when it came to improving visual acuity over one year.

This is the reverse of the positive midstage test that saw it best Lucentis as a monotherapy, when Fovista was also used alongside Novartis’ aging med, four years ago.

“We are very disappointed in the results from these trials, particularly for patients afflicted with wet AMD,” commented David Guyer, CEO of Ophthotech.

The future of this combo approach remains in the balance; Guyer added: “We will continue to analyze the data from these two studies to better understand the trial results,” but gave no other updates about the program.

This is also poor news for Novartis, which paid Ophthotech $200 million upfront, with a total of $1 billion in biobucks lined up, for ex-U.S. rights to its anti-PDGF candidate back in 2014. Novartis currently has ex U.S. rights to Lucentis, which is also sold by Roche. The Big Pharma recently opted in with Novartis to jointly have certain rights to Ophthotech's med with its fellow Swiss co. 

The biotech went public in 2013 amid a wave of new offerings, gathering $165 million, which ranked it in the top 10 biotech IPOs of the year as investors bought into the blockbuster potential of Fovista.

Both the IPO and Novartis deal were spurred on by the positive Phase IIb study in 2012. In this test, Fovista hit its marks as in combination with Lucentis, it significantly improved visual acuity when compared with patients using Lucentis on its own

Analysts at Leerink noted this morning that some KOLs and investors "did question whether the hurdle posed by the Lucentis arm in phase 3 may be higher than the phase 2, since the Lucentis arm appeared to have underperformed in that study."

As an anti-platelet-derived growth factor, or anti-PDGF, it is designed to stop the errant growth of new blood vessels tied to AMD.

The plan for Ophthotech has been to develop an efficacy-boosting add on to blockbuster eye medicines such as Lucentis, as well as newer offerings from Bayer/Regeneron in the form of Eylea (aflibercept).  

Lucentis and its rivals work by blocking vascular endothelial growth factor, or VEGF, and Ophthotech believes combining the two approaches could create a market-leading treatment option for the growing number of people with AMD, which mainly affects the elderly and can cause blindness.

Under its 2014 deal, Novartis had also planned to study a combination of Fovista with an anti-VEGF drug of its own.

In September, the biotech also had bad news when Regeneron saw a midstage combo failure wiith anti-PDGF beta rinucumab used with Eylea, failing also to beat Eylea monotherapy. 

There is another phase 3 test, expected to report mid-2017, that sees Fovista and Eylea with Roche's VEGF cancer med Avastin used together in a combo trial.

Leerink had seen a 65% probability of success here: "However, that estimate is under review in light of today's results. There is no specific reason to expect success in that trial, but it is a potential redeeming event for the Fovista program that we feel is prudent to mention," the firm said in the note. 

At the end of Friday trading, before the news was announced, the biotech was up 8.3% with a market cap of around $1.5 billion. This morning on premarket trading, however, the biotech was hit hard, down 80% from nearly $39 a share to under $8, while Novartis fell 0.6%.