Who dares stay in hepatitis C as another drug dies?
This article was originally published in Scrip
Merck & Co has informed the US FDA that it will stop selling its hepatitis C drug Victrelis (boceprevir) in the US by the end of this year.
Victrelis is of course a casualty of Gilead Sciences' hugely successful hepatitis C franchise, which includes Sovaldi (sofosbuvir), which was approved in December 2013, and Harvoni (sofosbuvir/ledipasvir), which garnered US approval in October 2014.
Victrelis was approved in May 2011, giving Merck precious little time to recoup its development costs for the product. But at least it reached the market.
Other pharmaceutical companies have had to make tough decisions over the past year to either their abandon their hepatitis C endeavors or completely change their commercialization models. The speed with which the hepatitis C landscape shifted caught many by surprise.
Vertex was the first to bow out (scripintelligence.com, 30 January 2014). Then Boehringer Ingelheim conceded defeat (scripintelligence.com, 20 June 2014). Novartis followed suit a few months later (scripintelligence.com, 2 October 2014).
However, some companies decided to stay and tough it out, notably AbbVie, J&J and Merck (despite this latest announcement).
the challengers
AbbVie recently had its all-oral regimen consisting of Viekira (ombitasvir/paritaprevir/ritonavir) and Exviera (dasabuvir) approved by the FDA as Viekira Pak (scripintelligence.com, 20 December 2014) and immediately priced it lower than Harvoni, knowing it faced an uphill struggle to achieve commercial success. There is now an ongoing battle for the hearts and minds of payers.
Johnson & Johnson surprised no-one this week when it admitted that it expected a "lower level of income" from its hepatitis C product Olysio (simeprevir) in 2015 compared with 2014 (scripintelligence.com, 21 January 2015).
But it did surprise some observers last year with its commitment to early phase development in hepatitis C, as demonstrated by the closing of the $1.75bn acquisition of Alios BioPharma during the fourth quarter.
Alios's antiviral platform includes a chemical library of nucleoside analogs. Since any Olysio-containing combination therapy that J&J might develop with Alios-discovered compounds will be years behind fixed-dose combinations from Gilead, AbbVie and other competitors, it would appear that J&J sees something in the Alios portfolio that could differentiate the big pharma's hepatitis C programs given the large, all-cash investment in the private company.
Alios said in September 2014 that it planned to advance the uridine nucleotide analog AL-335 into Phase I by the end of last year followed by initiation of a Phase I program for the purine nucleotide analog AL-516 in 2015. AL-335 showed potent inhibition of HCV in cell-based assays across hepatitis C genotypes.
"AL-335 and AL-516 could be combined with Olysio and an NS5A inhibitor that J&J bought from GSK (JNJ-56914845) in an attempt to compete with Gilead etc," Datamonitor Healthcare analyst Michael Haydock told Scrip. "This combination will be a me-too approach but at least it means that J&J has all the basic building blocks required to build a regimen that fits the new standard of treatment. Trying to position Olysio as an add-on to Sovaldi is not going to cut it anymore following the Harvoni and Viekira Pak approvals because it is just too expensive."
J&J sales data released this week showed a drop in sales from $796m in Q3 2014 to $321m in Q4 2014. "It looks like Olysio could go the same way as Incivek (Vertex/J&J's telaprevir) and Victrelis," added Mr Haydock.
acquisition opportunities?
Datamonitor has conducted an analysis of the remaining early-phase opportunities in hepatitis C (scripintelligence.com, 20 January 2015).
Its findings revealed that apart from Gilead, AbbVie, Merck and J&J, the only notable companies with early stage programs are Achillion with and Presidio Pharmaceuticals. Does this make them ripe acquisition targets?
"The obvious buyer for Achillion, which has early 'nucs', would be AbbVie, as everybody else already has nuc candidates," suggested Mr Haydock. However, "AbbVie appears to be going it alone with its second-generation protease inhibitor/NS5A inhibitor combo ABT-493/ABT-530."
AbbVie's partner Enanta has a preclinical nuc "so AbbVie might decide to try and license that," noted Mr Haydock. However, buying Achillion probably does not make the most financially sound strategy "because AbbVie would also be paying for sovaprevir (a protease inhibitor) and ACH-3102 (a non-nucleoside NS5A inhibitor), which would just be duplicating mechanisms of actions that it already has," said Mr Haydock.
Presidio, meanwhile, has signed a couple of interesting licensing deals in emerging markets for its NS5A inhibitor PPI-668 in the last year, hoping to shore up its future: one with Egyptian firm Pharco and another with Ascletis in China.
"We won't be seeing Presidio signing similar deals in major markets," stated Mr Haydock. "Its compounds don't have scarcity value like nucs do. PPI-668 is an NS5A inhibitor – everybody has these – and its candidate PPI-383 is a non-nucleoside NS5B inhibitor. There doesn't seem to be much interest in these in second-generation regimens, probably because nucs are preferred."