Are We Seeing Innovation In The "Me Too" Hep C Space?

By Anna Rose Welch, Editorial & Community Director, Advancing RNA

Sometimes we are up to our ears with signs of the industry’s competitiveness. This past week alone, for instance, we’ve heard the news that GSK’s HZ/su shingles vaccine performed well in its Phase 3 study, giving it an “unsurpassable edge” over Merck’s Zostavax monopoly in this therapeutic area.

In the immunotherapy space, sales figures released for Merck and Bristol-Myers Squibb (BMS) drugs revealed that BMS’ Opdivo was, surprisingly, the underdog, garnering $40 million for the first quarter of 2015 compared to Merck’s Keytruda, which raked in $83 million — $13 million more than investors expected for the quarter. (Something interesting to note: this upsurge is being linked to the fact patients received the drug via compassionate use trials, and, following its market release, chose to become paying customers, says Reuters. It’s not often we hear about the business perks of a successful compassionate use trial.)

So can you guess where I’m going next? That’s right — that the whirlwind hepatitis C therapeutic market seems to have accelerated in the past few weeks. When I think about industry competition, even the high-profile non-small cell lung cancer (NSCLC) immunotherapy race and the sprint to approve the promising PCSK9 inhibitors for cholesterol pale in comparison to hepatitis C. Perhaps this interest was born out of the drama of the AbbVie/Gilead/Express Scripts pricing hoopla, but it certainly seems this market has grabbed the industry’s attention and won’t let it go.

Now, not only do we have AbbVie and Gilead, we also have Merck, BMS, and Achillion Pharma making strides in the space. And, to keep things interesting and particularly whirlwind-ish, all released new data in the past two weeks (could that really have just been a coincidence?):

• Merck’s recently-renamed breakthrough grazoprevir/elbasvir combo resulted in a 99 percent cure rate in patients with chronic kidney disease (though it sounds like it’s actually closer to 94 percent given the company’s decision to exclude 5 percent of the primary efficacy analysis population because of death or non-treatment-related discontinuation of the trial).
• BMS’ post-transplant recurrence patient population receiving 12 weeks of treatment with daclatasvir plus sofosbuvir and ribavirin boasted a 94 percent sustained virologic response (SVR). Plus, patients with cirrhosis saw an 83 percent response rate from the regimen.
• AbbVie announced the FDA granted priority review to its New Drug Application for its ombitasvir, paritaprevir, ritonavir plus ribavirin regimen for genotype 4 (GT4) patients.
• Achillion Pharma, which was singled-out months ago by The Motley Fool as a biotech to watch in the hep C space, reported clinical results for its NS3/4A ACH-3102 (in combination with Sovaldi) and ACH-3422, its NS5B nucleotide polymerase inhibitor. In particular, ACH-3102+Sovaldi resulted in a 100 percent SVR after just six to eight weeks of treatment in patients with GT1.
• Gilead’s newest combo including Sovaldi and experimental NS5A inhibitor GS-5816 and the NS3/4A protease inhibitor GS-9857 showed that treatment-naïve non-cirrhotic GT1 patients experienced a 93 percent sustained response rate after six weeks of treatment. However, it’s important to note that success rates continued to decline as cirrhosis (87 percent) and treatment resistance (67 percent) were added into the mix. The short four-week run examining SVR was a failure, revealing only a 27 percent response rate.

In the past few months, pricing in the hep C market has been a common headline-stealer. But as companies continue to see good results for their treatments in shorter periods of time, perhaps attention on the competition in the hep C space will be redirected from price. Bloomberg so fittingly titled a recent article: “Need For Speed Defines Hepatitis C Race For Gilead, Achillion.”

The number of hep C genotypes (11), as well as complications including cirrhosis, HIV, and different viral loads from patient to patient, are all key factors in the length of time it takes to reach a cure, one expert told Bloomberg. However, the industry’s ultimate goal is to find one treatment that will span these differences, effectively treating a majority of hep C patients, while offering only one treatment time frame.

All of the flurry this past month, as well as the talk about seeking a single drug to meet the differing needs of many, has led me to think about the “me too” nature of the current market. There are the NS5A inhibitors (daclatasvir, GS-5816, and ACH-3102). There are the nucleotides, (Gilead’s Sovaldi and ACH- 3422, and though they’re not on the above list, we probably shouldn’t forget Idenix’s candidates IDX21437 and IDX21459, which Merck scooped up last year in its acquisition of Idenix). We also have the protease inhibitors (grazoprevir and GS-9857). It sort of feels like I’m listing the various cliques in a high school.

According to a Seeking Alpha article from last summer, nucleotides are the popular place to be — at least for Big Pharma. Seeking Alpha argued that, despite investor hopes that Achillion would one day be acquired by a Big Pharma company, Achillion was not a prime contender because it had not yet jumped onto the nucleotide bandwagon like the other hep C companies being acquired in recent years by Big Pharma, including Pharmasset, Inhibitex, and most recently Idenix. Instead of nucleotides, protease inhibitors were Achillion’s prime focus, which, according to Seeking Alpha, are still widely used, but are on their way out. The company does currently have a nucleotide inhibitor in development (ACH-3422), as mentioned earlier. However, if the treatment (currently in a Phase 1 proof-of-concept trial) should one day reach the market, there is always the fear it could be too late to garner a significant market share.

AbbVie’s Viekira Pak and Gilead’s Sovaldi are both currently approved for GT1 patients. BMS has its sights set on GT3, while Merck regained breakthrough designations by shifting its focus to patients with GT4 and those with GT1 with end-stage renal disease who are on hemodialysis.

Merck’s treatments might not be quite up to speed in terms of treatment time frame (cure rate took 12 weeks as opposed to the six for Achillion and Gilead.) However, the fact that its cure rate was high for a population with health issues besides hep C is certainly encouraging. Losing breakthrough status back in January because of the success rates for competitors was a big blow for the company; however, perhaps it was for the best so the company could redirect its attention to a smaller, more difficult subset of patients.

Similarly, while Gilead is still seemingly in the lead with its combination’s six-week 87 percent SVR rate for cirrhosis patients, BMS’ regimen is not far behind in treating those with cirrhosis, though the 83 percent response rate took 12 weeks to attain.

As Fred Poordad, a hepatologist and VP for academic and clinical affairs at the Texas Liver Institute in San Antonio told Bloomberg, “If you can treat that very difficult population, then by default you should be able to treat the easier-to-cure patient with that same regimen. It’s not a bad strategy to start with the most difficult groups.”

Over the years, pharma’s focus on “me too” drugs has led to concerns that these drugs are just distractions that are harming pharma innovation. However, it seems to me that there is still a drive for innovation in the hep C space — as witnessed by the slew of companies releasing their candidates’ progress one after another the past few weeks. While some of those reporting results were still focusing on 12-week regimens, the shift toward six- to eight-week regimens suggests that companies are attempting to bolster their candidates’ clinical benefits compared to those previously released to market.

I also think there is something to be said for the fact that so much attention has been lavished on the players in the hep C space. Each combination contains candidates from the same drug classes. But there is also a healthy sense of competition amongst the players for their share of the market, and setting sights on more efficient treatment timelines, I’d argue, does suggest these companies’ desires for continued innovation.