Subscribe to this blog's feedHoffmann-La Roche, a pharmaceutical company with a checkered history in AIDS drug development, has recently announced that they are ending their efforts against HIV/AIDS. Some activists have pointed to news like this in the past to warn that big pharma is about to abandon AIDS research in droves, because AIDS activists have given them too much grief, or forced them to give their drugs away in Africa, or that there's just not enough money in it for them anymore. Wrong, wrong, wrong.
HIV/AIDS always has been, and sadly, probably always will be, a profitable business. Pharma isn't going anywhere. Individual companies have come and gone, but that's true with any disease area. Over time, the overall pool of companies working in AIDS has actually increased, however slowly. In the late 80's, it was 2 to 3 companies, then 5 to 7 in the 90's, and now it averages around 10.
As long as overall antiretroviral sales average over $10 billion a year, industry isn't going to walk away. And with HIV infections continuing to rise, this is sadly a growth industry.
But back to Roche. They've always been one of the weakest links in the chain. They were the third company to bring an antiviral to market, with a me-too drug called ddC (Hivid, 1992), which followed AZT (Retrovir, 1987) and ddI (Videx, 1989). It paled in comparison, and eventually become the first AIDS drug pulled from the market due to lack of sales.
Then came the first protease inhibitor, saquinavir (starting as Invirase, then reformulated as Fortovase, then back to an easier-to-take boosted Invirase - at least they kept trying!), which quickly got out-marketed by stronger and easier-to-take PIs.
When they finally brought a useful AIDS drug to market, it wasn't even theirs! Fuzeon, the first entry inhibitor, became a crucial salvage therapy over the last five years, offering thousands of people with AIDS their last hope after becoming resistant to first- and second-line therapies. But another company, a small biotech called Trimeris, discovered it. They partnered with Roche to help them market it. Even still, the drug is now faltering as easier-to-take salvage therapies have hit the market.
Roche fumbled the development and marketing of all three of these drugs, working poorly with and infuriating AIDS activists along the way. I was one of hundreds of activists from ACT UP and TAG that completely blocked over a dozen entrances to their Nutley, NJ headquarters in February, 1993, protesting Roche's refusal to offer ddC on expanded access. Then they tried to abuse the accelerated approval process with saquinavir, causing a huge policy schism among AIDS activists over AIDS drug development and the FDA drug approval process.
Finally, they infuriated activists by pricing Fuzeon at close to $25,000 for a year's supply, the highest price ever charged for an anti-HIV drug. There were many demonstrations, but the company never budged on the price. We all cheered when Tibotec (Prezista, approved in 2006) and Merck (Isentress, approved in 2007) actually listened to AIDS activists and priced their salvage therapies at levels more typical of other HIV drugs on the market.
Roche got one big thing right. They have been a leader in drug development for hepatitis C, especially for those coinfected with HIV. Since almost a third of people living with HIV in the U.S. are coinfected with HCV, Roche's commitment in this area has been of huge benefit to our community.
For the record, here's Roche's letter to AIDS activists announcing their decision:
In response to your request, we are writing to provide further clarity on Roche's presence in the HIV field. Please share this information with other community members as you deem appropriate.As you know, Roche has a long-standing heritage of innovation in HIV since we initiated our protease inhibitor discovery project more than twenty years ago. Our work has resulted in major contributions in this field, among them the development of PCR diagnostic and viral load technology, the introduction of the first protease inhibitor, and the introduction of the first fusion inhibitor to patients in 2003 - despite the considerable technical challenges we faced in producing this very complex molecule on a large scale.
For several years, we have been investigating compounds targeting the CCR5 entry pathway and the reverse transcriptase enzyme. All these compounds were in pre-clinical studies, and therefore at least six years away from availability to patients. While we had initially been hopeful about their potential, we now have concluded that none would provide a true incremental benefit for patients compared to medicines currently on the market - and therefore do not warrant further development. We had hoped to provide you with this information in an in-person meeting.
Assessing this setback in the context of our overall Virology Disease Area, we have decided to refocus our resources within Virology on diseases in which we can deliver substantial improvements over existing medicines. However, when we identify a significant scientific breakthrough in HIV externally, we would certainly assess our ability to make a further contribution to the field, as we did with Fuzeon.
Developing new treatments for viral diseases continues to be a priority.
In particular, we have a promising pipeline of new drugs for the treatment of hepatitis C, which is one of the most significant causes of mortality among patients living with HIV. Furthermore, our scientists are currently examining a range of other viral diseases to determine those which offer the potential for us to make a difference.
Roche will, of course, continue to support our medicines that are currently available for the treatment and monitoring of HIV-related disease, including Fuzeon, Invirase and Viracept, as well as our molecular diagnostic tests. In addition, we remain committed to increasing the access to our HIV medicines for people living with HIV in resource-limited countries with programmes such as our preferential patent and pricing policy and the AIDS Technology Transfer Initiative.
If you would like additional information on the discontinued HIV programmes, we would be happy to engage in further dialogue with you.
SincerelyJenny Edge-Dallas
Global Leader, HIV FranchiseMike Nelson
International Communications Manager, Hepatitis and HIV
Hi Peter, there was also the saquinavir dosing debacle. In vitro, saquinavir is among the most potent PIs. This is a quote from the letter Mark Harrington wrote to Anne Collier, PI for ACTG 229, about the dosing issue:
"I remain perplexed about the current design of ACTG 229. In particular, I share the CTRC's (Clinical Trials Review Committee) concern about 'the selection of 600 mg tid [three times a day] as the dose of Ro 31-8959 [saquinavir] since there is no established maximum tolerated dose.' Doses as high as 1200-1800 mg tid have been tested in HIV-negative patients and found to be safe... but people with HIV have only been given doses up to 600 mg tid. I would concur with the CTRC that 'the need for the pharmaceutical sponsor to be forthcoming with data from their European trials' is pressing as we proceed towards opening ACTG 229."
A few years later, after the ACTG had been complicit in Roche's exposing thousands of people to suboptimal saquinavir doses (with attendant cross-resistance to other PIs), Tom Merigan did a study showing that higher dose saquinavir was tolerable and had far superior antiretroviral activity (on par with indinavir and ritonavir).
After [url=http://www.thebody.com/content/art47196.html?mtrk=9045233]this [/url]article I have read recently, come this news.
In the same time, as a "newly" infected person, I haven't follow-up in the last past years how well is going the research.
I just know from what I have read since few months that there are a lot of interesting research, trials, etc..
(OPAL, VRX496, TAT, 273 proteins inventory, GeoVax, HIV shortcut to reproduce, etc.)
I am wondering if compared to prior, if this amount of new good news are higher, same or lower than what ever before 2007.
Thanks for sharing,
John
I'm kind of torn on this one.
Based on your post, Peter, it would seem that there is no great loss here. Also as a matter of business (and we both have investment banking backgrounds) one less player means there is more money to be invested in companies that are producing results.
That said, I just can't see this as good news. Maybe I am missing something here.
After reading what you wrote as well as the first reader comment, it seems Roche had the clout and resources to be great, but they just couldn't get it together; and along the way, caused tons of heartache. A metaphor would be that "friend's friend" who's got mega-potential and cash, but due to odd priorities and bad choices, always seems to have one big life problem after another after another. But thank you for giving Roche credit where it's due. I learned alot from this, thanks.
John -- as far as the pipeline is concerned, I'd agree with Paul Dalton's analysis (see the link he provided -- http://www.thebody.com/content/art47196.html?mtrk=9045233 -- it's well worth reading) -- compared to recent history, it's pretty skimpy. We had a burst of new drugs hit the market over the last two years, so when they were in the pipeline, it was more flush than I had seen it previously.
That said, I remember that in years past, the pipeline could look skimpy at times, and then it would start to fill up again. It has ebbs and flows, like everything.
I do think you give far too much weight to pinning your hopes on compounds in early development. You'll find that old farts like me, and most other AIDS treatment activists, have learned the hard way how to keep those promising press releases and phase I trials in perspective. The vast majority never pan out.
The worst thing you can do is to start championing an early compound, drumming up a false sense of hope before the cake has actually been baked (in a controlled clinical trial). I'm not saying ignore them -- that would be equally lazy. But look at them with a healthy dose of scientific skepticism. Follow them, ask questions about them, report on them, but don't start a fan club for them before they've proven themselves.
Mark -- I agree, this isn't "good news" -- I never said it was. But it's not devistating news either, or signs of a worrisome trend.
I've received a couple of emails about this posting I'd like to share. Mark Harrington, TAG's ED, reminded me about the saquinavir dosing debacle, which has been well documented online:
http://www.aidsinfonyc.org/tag/tx/sqv.html
Also, another reader pointed out that I failed to mention an additional important contribution Roche has made in the field of AIDS -- Amplicor. This is the leading HIV viral load test we all take, and let's face it -- it would be hard to manage our disease without it.
In my defense, this post deals entirely with Roche Virology, and Amplicor comes from Roche Diagnostics, a separate entity within the House of Roche. But yes, they deserve kudos for this.
I haven't been involved in the struggles with pharma and HIV drugs, but there's something that creeps me out when someone's business title is "Global Leader, HIV Franchise"! I tend to think of a franchise as something like McDonalds.
Thanks for that TAG/saquinavir link, Peter. Unfortunately, as I stated in your AM thread, I'm one of those unfortunate folks who were put on this med when it first came out and developed cross-resistance to all PI's. Combined with the fact that for that first year my insurance policy would not pay for viral load tests until several "medical necessity" protest letters by my HIV specialist, by the time we saw what was going on it was too late. If we'd had those viral load tests I would assume my doctor would have switched me quicker to something else. Or at least I must assume that this is what happened. I'd read previously about this saquinavir mishap but this is more detailed.
I swear when I read stuff like this I wish I could sue.
Hi Peter, I stumbled across your blog for the Jesse Helms piece, but then found this one.
I just wanted to add my own perspective on the astronomical pricing of Fuzeon. I'm a chemical engineering grad student and had the opportunity last year to attend a conference at Roche and visit their production facility for Fuzeon. When Roche decided to try to produce this drug on a clinical scale, most people thought (some people still do think) they were crazy for trying. Fuzeon, aka enfuvirtide, is a linear peptide, a type of molecule most had assumed would never be pharmacologically or economically feasible for a drug company to develop and manufacture.
I make peptides as part of my research (admittedly for a completely different purpose), and I can tell you I was absolutely astonished at the complexity and cost of their Fuzeon plant. I do not mean that it was wasteful--their manufacturing process is incredibly streamlined and well-designed; nevertheless, peptide synthesis uses massive amounts of reagents and solvents and extremely complex and expensive purification methods for the amount of product you get out.
I am not trying to say that all $25,000/year was justified. But I do know that they could have only priced the drug so low before they would lose money rather than make money on it. Fuzeon really isn't anything like any other drug out there, and unfortunately, that uniqueness involves a great deal of added cost (not only from the manufacture, but also the research, development, and clinical trials required for a type of molecule that has never been used as a drug before) to both the company and the end user.
Boosted saquinavir literally saved my life, so I am not as down on Roche as others. Hivid (ddC),when combined with Zerit, also seemed to keep me healthy in the days before HAART. Saqunavir will be one of the first PIs to go generic and may provide a low cost alternative to Kaletra if Abbott ever lowers the price of ritonavir. The GEMINI study also showed boosted saquinavir/ritonavir to be comparable to lopinavir/ritonavir in efficacy with better lipid profiles. To quote AIDSMed.com, "Dr. Walmsley noted, 'These data are of considerable importance because they confirm that Invirase offers treatment-naïve patients an effective treatment to control the virus with significantly smaller increases in triglyceride levels than lopinavir, the most commonly prescribed PI.” http://blogs.poz.com/peter/archives/2008/07/roche_abandons.html
I wish I was in a position that I could ban their medications to spite them for giving up on finding better meds to help keep me alive!
F**K ROCHE! I do not feel sorry for them. They cannot handle the grief? Then get out of the business of medications!