Press Teleconference on Lopinavir/Ritonavir

Transcript of a press teleconference on the lack of availability of Abbott's new heat-stable Kaletra in African countries.

Speakers:

• Kate Evans, US Coordinator of MSF's Campaign for Access to Essential Medicines
• Nathan Ford, the Coordinator of MSF's Campaign for Access to Essential Medicines in South Africa
• Dr. Jens Henkel, a clinician in an MSF HIV/AIDS treatment project in Lagos, Nigeria
• Dr. Bintare Diawardiani, the Medical Coordinator of MSF's projects in Homa Bay, Kenya
• Daniel Berman, MSF's Access to Essential Medicines Campaign

Kate Evans:

Thank you – thank you to everybody for joining us today. I would just like to begin by welcoming everyone as we discuss the need for newer antiretroviral (ARV) medicines to treat HIV/AIDS in developing countries. And in particular, the need for Abbott Laboratories's new heat stable formulation of lopinavir/ritonavir which is marketed as Kaletra. Currently MSF provides ARV therapy to nearly 70,000 patients in 51 projects across 31 countries. And what is important to understand is that as patients spend more and more time on treatment, it is inevitable that they develop resistance to the HIV medicines they're taking. And so, like in the U.S. and Europe, our patients and thousands of others on treatment need access to newer drugs to continue to be able to fight HIV.

The new formulation of lopinavir/ritonavir by Abbott Laboratories does not require refrigeration which makes this a critical component of the second-line treatment regimens we use. And it makes it one of the very few options that we have that are actually adapted for use in developing countries. However, today this drug is only available in the U.S. Because MSF has an urgent need to provide this drug to our patients, we have placed an order today with Abbott's worldwide headquarters in Chicago to meet the needs of our patients.

To discuss this issue further we will be speaking with Nathan Ford, the Coordinator of MSF's Campaign for Access to Essential Medicines in South Africa. Dr. Jens Henkel, a clinician in an MSF HIV/AIDS treatment project in Lagos, Nigeria,, and Dr. Binta Diawardiani, the Medical Coordinator of MSF's projects in Homa Bay, Kenya. We will hear from each of our speakers for just a few minutes and then open it up to questions.

So at this point I'd like to turn it over to Nathan Ford.

Nathan Ford:

Hi, thank you, Kate. Thank you to everyone for joining us.

I'm sitting in South Africa at the moment. I'm working in an HIV program where we have two sites treating patients. One is in the western cape near Cape Town where we treat three-and- a-half thousand patients. And the other in the eastern cape, in Lusikisiki, where we have another one-and-a-half thousand patients on treatment. We've been working here for about five years. And we've been seeing that the general trend is a need for second-line drugs after four years of treatment on first-line medicines. Today, around 16 percent of patients need second-line treatment. We can be pretty sure that that's going to get higher and higher as time goes on.

Here in Lusikisiki in the Eastern Cape it's around 37 degrees Celsius [99 degrees F]. It's a very, very hot day. Half the clinics have no electricity and certainly most of the people we're helping have no refrigerators. So this second line drug that we're pushing for today, the lopinavir/ritonavir combination that doesn't need to be refrigerated, seems to me to be designed for use in Africa, precisely in these sections where people don't have refrigeration or electricity. And it's very frustrating for me to consider that this drug might not be available in Africa for many, many years to come. So we think it's important that Abbott make clear commitments to making this drug registered and available and affordable as soon as possible.

Now it's not just MSF in South Africa that needs this drug. There have been clear demands from physicians all over South Africa and in fact from many other countries who have signed on to a letter to try and push Abbott to make these commitments. We have physicians from roughly 25 countries that have signed on to a letter demanding three things from Abbott. The first is that Abbott takes seriously the registration of this drug. One of the problems with accessing drugs is that they might be available on the general market, but unless the company actually takes steps to register the drug, the public sector cannot use those medicines and that can lead to several years' delay. We've seen it with other medicines and we're very, very concerned that we're going to see that problem with this medicine. So they need to submit registration requests immediately so that the drug can be used in the public sector as soon as possible. Second, we want Abbott to work on finding interim solutions so they don't just file the dossier and then sit on their hands and we have to wait two years before the drug is registered. We need to make absolutely certain that strong interim measures are in place so that we can start using this drug as soon as possible. And then, finally, we need to make sure the drug is affordable. I understand that currently the market price for the drug in America is around nine-and-a-half thousand dollars. Now, that's a price that nobody in this country can afford and we need to make absolutely sure that the company is making firm guarantees to roll out this medicine at an affordable price.

As I say, it's a drug that we need right now in our programs in South Africa, but we're going to be needing it even more because as the number of patients on treatment mature – and more and more patients have been on treatment over time – then more and more of those patients will have to move from the older medicines to the newer medicines. So it's an acute need for us now, but it will be an even greater need as time goes on. We're taking this course of action today because we see an ever increasing problem.

Kate Evans:

Thanks very much, Nathan. And now we'll hear from Dr. Jens Wenkel, who actually just came from a press conference in Lagos, Nigeria and is treating patients in our HIV/AIDS project there.

Dr. Jens Henkel:

Hello. Thank you and welcome to everybody. Greetings from Lagos. I'm working here as a doctor in Lagos where right now we have 1,200 patients on ARV treatment. We have started them on the first-line regiment recommended by the World Health Organazation. The problem in our project is probably the same faced by many others right now and will face in the future: about 10 percent of our patients are in need of a second-line treatment because of therapy failure That means if they run into clinical failure and develop all kinds of infections, we don't have a really stable and efficient second-line treatment for them. So we feel responsible as an organization, and as well as physicians, to not to let the patients down and provide an effective second-line regiment.

Now the cornerstone drugs recommended from the World Health Organization (WHO) in second-line treatment are protease inhibitors (PI), like the lopinavir/ritonavir combination, marketed as Kaletra. A major advantage is that it has two PIs in one tablet, but the major problem with the old version is that it is not heat stable. So we are obliged to store it in the fridge. As soon as the medicine is taken out of the fridge, the company says we can only handle it under 25 degrees for six weeks. We fear that most of the time it is handled at more than 30 or 35 degrees — which means after some weeks the drug's activity goes down and we have seen it even clump together so the patient can't take the drug out of the boxes anymore.

Right now we have about 100 patients in need of effective second-line treatment. And we project that by July 2006 we're going to have 140 patients. The problem is that they don't really have time, and so we need this heat-stable version of Kaletra now. We have so far reached one patient with the old version. Just to give you a practical example of how difficult it is, I'll mention his story. He really has no power at home because the power situation in Lagos is very difficult. So he needs to run generators and he has problems with the switches. So he stores the medicine in our clinic and comes on a daily basis to get his drugs. If we look into the 100 other patients in need of second-line drugs, then it becomes very, very difficult to make sure that the older version is stored under proper conditions. We really urge Abbott to make the thermal stable version available here. And as Nathan Ford mentioned before, it's ironic that African patients have no access to a second line drug designed for an African setting.

Kate Evans:

I want to thank you for that and to clarify that the temperature measurements are all in Celsius. We'd like to move to Dr. Binta Diawardiani, who will speak briefly about the situation in Kenya and what the recent ministry of health there has decided versus MSF's forced protocol.

Dr. Binta Diawardiani:

Thank you, Kate. Welcome, everybody. In Kenya MSF has four HIV care programs. I worked for one year in Homa Bay. Today we are caring for 5,000 patients. Right now we have a very few number of patients taking second-line treatment, but soon we will have more and more. In Kenya, the Ministry of Health started a scaling up process for treatment in January 2005. And they released new guidelines in November 2005, which follows the WHO guidelines for ARV treatment.

MSF and many providers cannot provide the older Kaletra to many of our patients because they are too poor to buy it and the temperature in the area where we work is far above the recommended one. And we don't see how to offer better treatment to those who have enough money to buy it. So currently we are still using Nelfinavir. Of course Kaletra is better because the pill burden is less and there is no dietary restrictions — both factors that can sometimes interfere with our patients adhering to the treatment. So we really need this new heat-stable version of in Kenya.

Kate Evans:

Thank you, Dr. Biawardinia. I appreciate your explaining the situation in Kenya and in particular how MSF is actually not able to follow the Ministry of Health guidelines at this point because we do not have a heat stable formulation of this critical drug available to us in Kenya. And at this point I would also like to open it up to any questions for our speakers.

Questioner 1:

Thank you. Have there been any discussions with Abbott Laboratories? Is it just Abbott in this case and have there been any discussions at all and what have they said?

Kate Evans:

At this point we have made a request in the beginning of the year to speak with Abbott Laboratories, specifically on their plans to distribute this new formulation outside of the U.S. and to understand what price they were going to make this drug available at. We received very vague responses, which is to say that they committed to at some point in the future pursuing registration, but insisted that registration was necessary first in Europe because of the requirement for a Certificate of Pharmaceutical Product. We looked into this issue further and have additional information available on our website which we can certainly get to you about the myth of this Certificate of Pharmaceutical Product. And what is actually the case is that Abbott, if it wanted to export this drug right now from the U.S., it could do so and request the Certificate of Pharmaceutical Product from the FDA and begin the registration process now. Instead, Abbott has taken a commercial decision to wait until the EU approval comes through so that they can export from Germany. This represents additional delays to us that are unacceptable. And so in our communications with Abbott the fact that they talk about beginning the process of registration at the end of 2006 or the beginning of 2007 are completely unacceptable because of the reasons you've heard today from Kenya and Nigeria in terms of the numbers of patients that need this drug now.

Nathan Ford:

To add, we have tried to negotiate with Abbott, but what they have said to us so far has been extremely vague and non-committal. The registration issue, I can't emphasize enough how much of a blockage that is to accessing the medicine. The time between submitting the registration and getting registration in South Africa is roughly two years. And right now our understanding from Abbott is they said they were going to submit for registration the end of last year, beginning of this year, but they still today have not done so. So the longer they wait to submit, the longer we wait for the drug to be registered. And until the drug is registered it's not available at all. The second issue, of course, is price. We want a firm commitment from Abbott that they will make it available at a greatly reduced price, certainly nothing like the price that's being charged in the U.S. and Europe at the moment. And, again, we don't have any firm commitment there. So that's why we're upping the ante, so to speak, and trying to put pressure in a more public way towards Abbott. And finally, we need this drug today in our project, so we have placed an order for these medicines for a number of countries that need the drug. And we're hoping very much that Abbott will respond by ensuring that the order that we've placed will be serviced at an affordable price.

Questioner 1:

Even if they agree to this, the availability would still be two years down the line? And the order that you've placed, have you placed it based on purchasing it at the present price if it's not available at a cheaper price?

Nathan Ford:

I'll respond to the time question and if it's okay, I'll let Kate respond to the price question. The time between submitting and getting a drug registered differs from country to country. So when I said two years, that's roughly what it takes in South Africa. And as I've mentioned, it's also incumbent upon the companies, I think, to work to find an interim solution. So to work not just to submit the dossier and then put the burden of responsibility entirely upon drug regulatory authorities to do the registering of the drugs, but to actually work with the regulatory authorities to make sure the drug is registered as soon as possible. Avian Flu has been a good example of many dynamics in the drug market. But in South Africa it's notable that the avian flu drug, Tamiflu was registered very, very quickly, within a matter of months, in fact. So how long it takes to register a drug is also a matter of political priority and it's also a matter of to what extent drug companies cooperate in that process.

Kate Evans:

And just regarding some more specifics on the order that was placed today by MSF. It is for patients treated by MSF in nine different countries, which encompasses, by the end of 2006, enough treatment for 800 of our patients. And it's really just an initial order. It does not represent the total need, but specifically the countries that were included in that list were countries in which we can easily get and have already started in many cases the process of special authorization to overcome the barrier to registration, because Abbott has not begun that process themselves. And so rather than waiting for months and years, we will go ahead and get special authorization to use this drug in country because of that need.

Regarding the price question, we're asking Abbott for a price no greater than the price they charge for the original formulation in developed countries, which is $500 per patient per year. We see no reason that the price for the new formulation should be above that and want the most affordable pricing for our patients and others.

Questioner 2:

This registration process, does that mean that even if you guys get the drug from Abbott and want to distribute it, you can't? I mean, what would happen if you tried? Would it be stopped at the borders? Would it be taken out of your clinics?

Nathan Ford:

So, again, to take the example from South Africa. We currently face this problem with another anti retroviral, Tenofovir. The way we access that drug is through special authorization. It's on a named-patient basis. And we have to apply for use patient by patient to the drug regulatory authorities. So it's possible and completely legal to use drugs that are not registered, but you have to go through a very complicated and lengthy bureaucratic process. MSF is an international organization and so is able to jump through all those various hoops which include also importing drugs from another country, because if a drug isn't registered then it can't be stocked in country either. But it excludes use of that drug in the public sector. So we're using Tenofovir today, but most of our public sector physician counterparts are completely unable to use that drug and they have to wait for registration. And it will be the same case for the new Kaletra. We will be able to use that drug legally but it won't be a mechanism that will make the drug more broadly available.

Questioner 2:

And can I just follow up? Where are you with Gilead on your fight about Tenofovir?

Nathan Ford:

We're still waiting for the drug to be registered and we're still waiting for Gilead to propose an interim solution that is more quick and cost effective than having to ship the drug from California.

Daniel Berman:

Can I address that question? Regarding Gilead, one of the problems is they had given voluntary license to Aspen, which is a generic drug company in South Africa. Aspen needs to file for registration. So the company had two paths. One would have been that they could have registered the existing product and it would have already been on the market in South Africa and other countries. But in fact they've waited for this generic company and so far the company, Aspen, doesn't even have a product that they can request registration for.

So, in other words, Gilead still has not even filed in many of the countries in Africa and they haven't even started that process. So I think we have a similar problem in terms of Gilead as we do with Abbott.

Questioner 3:

Is Kaletra used only as second line therapy or is it used as first line therapy in its present formulation? And can somebody explain – I thought I read in the letter that this is actually a cheaper process — to make it heat resistant. So I'm curious about that.

Daniel Berman:

I can try to address both questions. First, there was a group of experts who met at the World Health Organization in July. And the WHO is going to be releasing new guidelines for resource poor settings. The draft of that is already available on their website. And it recommends only boosted protease inhibitors, ones that have ritonovir in them for a second line. So the clear answer is that this drug is recommended for second line. The situation we have now is that the drug we have been using is no longer recommended. We had been using Nelfinavir because it's the only one that you don't have to refrigerate. But the new guidelines say that that's not recommended anymore. They recommend boosted drugs, and the only boosted one that doesn't have to be refrigerated is this new version of lopinavir/ritonavir.

Kate Evans:

I would just like to add that those guidelines are specific, as Daniel said, to resource-poor settings. So in the U.S. and Europe you may find people living with HIV who are taking lopinavir/ritonavir as their first-line medication.

Daniel Berman:

And regarding the cost of production. We did some investigation. Of course, MSF doesn't have the expertise to know about production. So we went to the experts. We went to the World Health Organization. We went to Chinese drug manufacturers and we went to Brazilian drug manufacturers. And they all had the same conclusion that this technology at high volumes would have a lower cost of production per unit. And very simply put, that's because the technology is actually put several steps into one machine and so you don't have the loss of the product between each step. That's one of the key reasons. And so the experts say that at high volumes this product would be less expensive to make.

Questioner 3:

Just a quick follow up on that then. Are you suggesting then that once this heat resistant formulation of Kaletra is available that this will become first-line therapy?

Daniel Berman:

No. What I was saying is that the guidelines talk about use of protease inhibitors as second-line. And I think what Kate was referring to was that in the U.S. and in Europe patient care is more individualized and physicians may decide to put patients on protease inhibitors as first-line. But I think there's more or less a trend to use non-nucleotides as first-line and to save the protease inhibitors. I think that's the way things are moving in general. And in terms of the WHO guidelines, they've actually put that into writing and said that these drugs are meant for second line. That's their recommendation.

Questioner 1:

Does anyone know whether any of these drugs are available through PEPFAR, the second line treatments. Do they make them available?

Kate Evans:

I can answer that to a certain degree, but part of the answer is no. PEPFAR at this point does use Tenofovir. And we have been speaking with representatives of PEPFAR, particularly regarding the use of heat stable lopinavir/ritonavir to see if grantees would be importing that drug and that that would be a way to accelerate access through the PEPFAR program. At this point they have no plans to make special use of the new heat stable lopinavir/ritonavir, although this could change if particular care providers wanted to make sure that this drug was available to their patients.

Daniel Berman:

I think that that for us is a real problem: that the U.S. government is sending the old formulation which we know is not adapted to a lot of places, because as we said, it melts at high temperatures. So it's a real problem that the U.S. government is paying for the old formulation and not pushing for the new formulation.

Kate Evans:

I'd like to thank everybody for staying with us and we will follow up with any additional information.