Welcome to your weekly digest of approaching regulatory and clinical readouts. Data from Actelion’s selexipag in pulmonary arterial hypertension (PAH) are due in the coming weeks. The company is expected to lead the market with Opsumit, but with the loss of Tracleer imminent selexipag needs to prove a mortality benefit to stay ahead of the rest.
Meanwhile the PDUFA date for QRxPharma’s MoxDuo IR is May 25. The dual opioid received a unanimously negative FDA panel vote last month that crushed shares, and with two previous complete response letters another is likely, meaning that the future looks bleak for the Australian company.
The phase III Griphon trial is in 1,156 patients with symptomatic PAH. Last May an interim analysis concluded that the trial should continue as planned. Final results are expected in the second quarter. Selexipag is an oral prostacyclin agonist, and the primary endpoint in Griphon is time to PAH progression or death.
Actelion’s leading growth driver, Opsumit, is an endothelin receptor antagonist, is expected to become the biggest PAH drug by 2016. It was the first PAH drug to get a mortality claim on its label, and this is a benchmark that selexipag will also need to hit. The company has said that it "very much expects" to see a mortality benefit.
In a small phase II study selexipag produced a statistically significant reduction in pulmonary vascular resistance, but no definite findings on mortality or morbidity have yet been released.
Selexipag’s mechanism of action is well validated; however, other marketed prostacyclin analogues suffer from poor pulmonary selectivity and a short half-life, which requires continuous infusion or multiple inhalations, meaning that they are usually reserved for late-stage patients who have failed alternative oral treatments.
Selexipag’s oral administration has obvious advantages over others. United Therapeutic’s Orenitram, another oral prostacyclin agent, approved at the end of last year, had less than impressive clinical results and is only approved to improve exercise capacity in patients; it cannot be used in combination.
Selexipag is Actelion’s second-biggest growth driver behind Opsumit. EvaluatePharma consensus 2020 revenue forecasts are $363m, and Jefferies analysts forecast $800m peak worldwide sales assuming 20% penetration of PAH patients as a combination therapy, in addition to a minor share of new patients as monotherapy.
Leading the revenue stream for Actelion is its other PAH drug, Tracleer, which had $1.6bn last year. But with the impending loss of patent protection forecasts plummet to $137m in 2020, according to EvaluatePharma. But Opsumit is now in place to help fill the gap, with 2020 sales forecast to reach $1.5bn (Actelion gains breathing room for Opsumit push, March 17, 2014).
Takeover speculation has surrounded Actelion for a number of years, and the imminent readout from selexipag could see buyers finally come knocking.
QRxPharma: MoxDuo IR
Moxduo immediate release (IR) is a combination of morphine and oxycodone for the treatment of moderate to severe acute pain. It is unlikely to enjoy an immediate release onto the market: an advisory committee recently recommended against approval of the dual opioid, voting 14-0, prompting QRxPharma’s shares to tank 80%.
The panel said the company had not provided evidence that Moxduo was safer than its individual components at comparable doses. Documents from the panel note that the FDA has never before approved a combination of two drugs from the same pharma class, because of a rule to assure that a combo provides some benefit to patients that could not be obtained by prescribing the individual components alone.
QRxPharma was aiming to highlight the specific benefit of improved respiratory safety with MoxDuo IR. Respiratory depression is one of the most serious adverse events associated with opioids, but the FDA did not agree that MoxDuo IR provided an advantage.
The end is nigh
MoxDuo has had a dire history, receiving a complete response letter in 2012, followed by two formal dispute resolutions and then a second CRL last August. Regulatory review for opioids will always be stringent as the FDA continues to battle the possibility of abuse with long-term use (Further FDA crackdown on opioids could close market to generics, September 11, 2013).
In an investor call after the adcom QRxPharma’s then chief executive, John Holaday, said the group was “determined to press on with the process and make sure this drug makes its way into the marketplace”. Since the call Mr Holaday has been replaced by the company’s chief operating officer, Edward Rudnic.
Two further versions of MoxDuo, controlled-release and intravenous, are in phase II. However, with the FDA having such an entrenched view on the project there looks to be little good news on the horizon for QRxPharma.