The Hepalogue

The Balm of Gilead, Pill Burdens and The Viekira Pak

by The Golden Phaeton on 05/06/2016

Gilead Sciences, those Wise Masters who reign over Harvoni and its two ingredients – ledipasvir and sofosbuvir (AKA Sovaldi) – are the mightiest of Big Pharma’s tentacles to penetrate the world of Hep C.

I liked to think, until I began writing this, that the company was named after The Balm of Gilead – either a rare and ancient perfume, a universal panacea, or both, which is mentioned a number of times in the King James Bible.

The precious balsam (balm) is said to have grown only in two small gardens near the doomed city of Jericho. It served a sacred function, perhaps still does, in both Jewish and Christian rituals and, notably, was given to King Solomon as a gift by the Queen of Sheba. Paleo-botanists remain uncertain exactly which shrub produced it; though most believe it oozes from the same bush as the fabled Balsam of Mecca.

As for the drug company, it was named, rather drearily, after a cafe which featured in a play called Balm in Gilead. Written in 1965 by US playwright Lanford Wilson, it features ‘the underworld adventures of the patrons of the namesake cafe‘. A shame. I preferred the more exotic explanation.

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Why am I talking about Gilead Sciences? Because their flagship drug – sofosbuvir – has, for the first time shown a year-to-year slump in sales. This might seem crazy, considering how many are using the drug – at least in our part of the world – but it has been suggested that the wind may might have left the sails of the frenzied Hep C treatment industry, which at one point was supporting the development of over a hundred new drugs.

But, to quote Bloomberg, HCV is not going anywhere. And Gilead, together with any number of other big pharmaceutical companies, is far from ceasing research into Hep C treatment. Since the first interferon-free DAA-based therapies appeared towards the end of 2013, Big Pharma has raked in a combined USD 38 Billion – and there is plenty more to be had. In case you didn’t know, it is wild down in the fighting pits of Hep C drug development. The giants of big pharma are running a very fast game, powered by god-awful sums of money.

Currently, Gilead remains the star, massively outselling all other Hep C medications. And one would assume they are making hay while the sun shines, shoring up their markets, putting the whip to their R&D department, fattening their purse for acquisitions – as they drain every last gem of profit from their ageing wonder drugs.

Of course, the days of sky-high profits will not last forever. Region by region, Gilead’s patents will lapse. Operations like the Hep C buyers’ club are funnelling away potential earnings from rich countries without universal health care – to a point where, according to buyers’ club founder Greg Jefferys, Gilead have established a ‘crisis team’. In Australia, it is rumoured that once our health system has forked out an agreed amount on Gilead merchandise, all subsequent purchases will be free – creating an effective limit on the profits to be gained in this country.

But all of this is small change compared to the threats posed by Gilead’s competitors within Big Pharma (and, to be accurate, Big Biotech).

Indeed, another shiny new regimen has already arrived. On the first of May, two months after the first new therapies were heralded into the Pharmaceutical Benefits Scheme, AbbVie’s exotically-named multi-drug regimens – the Viekira Pak and Viekira Pak-RBV (with Ribavirin) – were also listed.

The Viekira Pak contains four drugs – Paritaprevir, Ritonavir, Ombitasvir (combined in a single daily pill) and Dasabuvir (twice daily with food). It boasts a similar overall cure rate to the sofosbuvir-based treatments, but for people without cirrhosis some studies show it edging on 100%. All the components are new DAAs, but for ritonavir – an older anti-retroviral agent still used against HIV in a tailored combination called HAART (Highly Active Antiretroviral Therapy). Though ritonavir has been associated with some unpleasant side-effects among HIV patients, it appears that – at the dosage used to treat Hep C – these rarely occur.

As a general rule, the Viekira Pak is well-tolerated. There does seem to be a local perception that it is slightly more likely to produce side-effects, but I suspect this impression is mainly derived from anecdotal evidence. Ultimately, clinicians in Australia see no particular advantage in taking one combination rather than the other. (One reason a patient might be prescribed the Viekira Pak is if they have difficulty remembering to take the drugs. Though there is technically more of a ‘pill burden’ with the Viekira Pak, the medication is very intuitively packaged.)

The Viekira Pak targets genotype one. This is to be expected. Most of the Big Pharma players tend to focus on genotype one because it is has the widest distribution, particularly in developed countries (though it is still outnumbered by the sum of of other genotypes) and therefore offers the juiciest profits.

Even allowing for a shorter period on the market (and a vicious price war in the US) the profile of AbbVie’s new drugs remains low. There was somewhat of a sharemarket kerfuffle last year when authorities in the US released a liver toxicity warning for the Viekira Pak. A small number of patients, usually with cirrhosis, were experiencing elevated ALT levels, mild jaundice, sudden liver decompensation, and death.

AbbVie’s share value sank while Gilead’s surged. A portfolio manager for a US healthcare fund – seemingly bereft of any moral compass – described the toxicity warning as ‘a huge positive for Gilead‘.

Strangely, the same report mentions similar episodes among users of Gilead and BMSs’ oral antiviral combinations, saying that – this phenomenon may be unrelated to a specific agent, but rather common to all potent antiviral therapies for hepatitis C and perhaps is a paradoxical response to sudden clearance of HCV.

(Interesting. It immediately makes me think of two friends of mine, both with genotype three, who experienced unusual liver pains during the first few weeks of treatment. One told me it felt like his ‘liver was reshaping itself’. Certainly sounds like a ‘paradoxical response’ to me.)

Whatever the case, extreme outcomes are rare and far from sufficient to destroy the reputations of such successful treatments, or threaten their withdrawal from the market.

In truth, AbbVie’s future is actually looking golden. In recent news, outstanding results have been recorded for their potent, pan-genotypic combination of new inhibitor molecules (ABT-493 and ABT-530 ). In one study, over a brief eight week period, across genotypes one through three, the drugs achieved a 97-98% success rate. Given an extra four weeks (and no cirrhosis) the treatment seems to mop up genotypes 4-6 as well.

Gilead has another looming competitor in the pharma giant Merck and a combination therapy called Zepatier (elbasvir/grazoprevir) which treats genotypes one and four. As third in line, Merck has adopted a competitive pricing strategy, making their product 42% cheaper than Harvoni , breaking ‘an unspoken gentleman’s agreement‘ among drug companies that ‘until generic competition comes along, companies price similar drugs in a similar – usually high – range, giving them a bigger pie to split‘. 

At least Merck won’t have to face the extreme criticism levelled at Gilead for the fantastically high price of their life saving medications. They are also working to find niche markets for Zepatier which include ‘patient populations where significant unmet medical need still exists, such as prior treatment failures, as well as those living with co-morbid conditions, including HIV infection and advanced chronic kidney disease‘. Predictably, Merck has a new super-combination in the works, hopefully due for release in 2018.

A recent report suggested that Zepatier could be leading the pack in terms of safety, but this immediately precipitated a cat fight with Gilead who, with some justification, challenged the results. The upshot is that all three companies, at this stage, appear to have products which are well tolerated. Basically, there is no reason to fear taking them, or to hold off hoping for the appearance of safer options. Perhaps you will be unlucky enough to experience a rash or an occasional headache, but the chances of you contracting, say, progressive multifocal leukoencephalopathy are beyond vanishingly small.

Many ‘price-wars and market-share brawls‘ lie ahead, as companies spar for their slice of the golden pie, but – for we humble patients, with our simple requirements – it looks like the wondrous treatments we are getting today will seem crude by the end of the decade – and that, in time, Hep C will become little more than a bad memory.

The Golden Phaeton.

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