Welcome to your weekly digest of approaching regulatory and clinical readouts. The next couple of weeks is set to be busy at the US FDA as decisions are expected on Johnson & Johnson's hepatitis C project simeprevir, as well as Galenica and Fresenius’s phosphate binder PA21.
One PDUFA decision, on Forest Laboratories’ cariprazine, came earlier than expected, but yesterday resulted in a complete response letter for the anti-psychotic project. The news has left Forest with one less option to plug the hole left by the expiry of Lexapro's patent last year.
Analysts at Leerink Swann estimate that Forest is now looking at a two-year delay for cariprazine, which had been forecast to contribute $280m in sales by 2018 and was slated to become the sixth-biggest growth driver at the New York-based company.
Adverse events are worrying the FDA, which has asked for more trials to find the optimal dosing that retains efficacy but minimises side effects.
Cariprazine differs from other anti-psychotics in that it is a dopamine D3/D2 partial agonist, with a partcularly high affinity for D3 that could be causing the side effect and tolerability issues. The biggest side effect was akathisia, or restlessness – an undesirable symptom to promote in schizophrenics.
Regulatory success is expected for J&J, however, which is hoping that simeprevir, now named Sovriad, will provide it with a springboard to participate in the growing combination of hep C drugs that are slated to hit the market over the next few years.
A unanimous advisory panel vote in October means that the agent, licensed from Sweden's Medivir, should be a shoo-in for approval by its November 28 PDUFA date. While it will likely be indicated in combination with interferon and ribavirin for adults with genotype 1 hepatitis C, like others in the space its potential lies in interferon and potentially ribavirin-free regimens.
This combination use could come sooner than expected given the positive results from the Cosmo trial, where it was used with Gilead Science’s sofosbuvir and achieved viral suppression rates of 90% without ribavirin or interferon. Off-label use of the two drugs together is expected once sofosbuvir is approved in early December (AASLD – Sofosbuvir-simeprevir pairing scores big, November 5, 2013).
Also up for approval by December 1 is the phosphate binder PA21. This was originally developed by Vifor Pharma, then rolled into a joint venture between Galenica and Fresenius Medical Care.
The iron-based treatment is targeted at kidney dialysis patients who face a build-up of phosphate in the blood due to their illness, and works by adsorbing the dietary phosphate in the gut, preventing its uptake into the blood. The adsorbed phosphate is then excreted.
While PA21 is set to enter a space that will soon see generic competition, it has the advantage of a lower pill burden than other therapies. Patients need only take three chewable pills instead of the nine for other therapies. Given that kidney dialysis patients can take up to 50 pills per day, any reduction is welcome.
However, PA21 faces a very narrow window of opportunity, as the biggest-selling brand currently, Sanofi’s Renagel, loses patent protection next September, while another novel product, Keryx Biopharmaceuticals' Zerenex, could win approval in June (Therapeutic focus – Phosphate binders seeking safety in small numbers, December 08, 2010).
PA21 will be sold by Fresenius, while Galenica gets 55% of the profits under the deal. Analysts believe that Fresenius's strong position in dialysis provision should give PA21 an advantage over Zerenex, but the arrival of generics makes the potential of both products hard to predict.
Consensus forecasts from EvaluatePharma show sales of around $300m for Zerenex in 2018, while Galenica is seen receiving royalties of $145m in the same year.