Fw: NATAP: New HIV Drug Development-a problem

[Guest guest]

from Jules Levin: In the past few years we have seen development of a number of very effective new HIV drugs: raltegravir, darunavir, etravirine, Fuzeon, tiptranavir, and CCR5 inhibitor maraviroc,  with TMC278 on the way. Tibotec has been very busy developing 3 of these drugs along with a comitment to HCV drug development. Merck displayed quite a high level of commitment to developing raltegravir and also to developing new HCV drugs. All these companies spent money and effort developing these very important HIV therapies. Pfizer developed maraviroc as is Schering Plough developing their CCR5 antagonist vicriviroc, but to a market that has been lukewarm so far to using CCR5 inhibitors. Boerhinger Ingelheim developed and launched tipranavir when Fuzeon was the only new drug, and they too have an active HCV drug development program. At the time patients were very anxious for both Fuzeon and tipranavir. Of course Roche's development program of Fuzeon was a trailblazer in new drugs for patients with extensive drug resistance and saved quite a lot of lives.I sat on the company community advisory boards for al these drugs and witnessed the process companies and patients experienced in develoment for each of these drugs.  At ICAAC Nov 2008 there was an oral presentation by the FDA in essence laying out study requirements for new HIV drugs. It appears as though the FDA and the EMEA have created high barriers for new HIV drug approvals. It also appears as though many HIV researchers/'thought leaders' think we have enough HIV drugs and agree with these high barriers for new HIV drug development. I emphatically disagree. We need safer, more convenient, drugs with less side effects. We need new classes of drugs that have these characteristics and for patients with drug resistance. In the past I recall there was a movement to fast track new drugs for patients with resistance and I think this helped in the movement to delay studies in naives. This I think helped put naive drug development in a context that it was less important. More recently a number of well known HIV researchers have made their opinions clear that they think we have enough new HIV drugs and this has played an important role in creating high barriers for new drug development. This development certainly adds to an environment where additional factors discourage new HIV drug development. Developing a new HIV drug is costly, and there are already about 20 HIV drugs so these facts make it potentially much more difficult to justify investing the high cost for developing a new HIV which has been estimated at $500-750 million to develop a new HIV drug. Of course in addition due to economic reasons all companies are in a situation of having to tighten their financial belts and make decisions about where to invest their research dollars and decide I think where will they make a better profit -- cancer, HIV, cardiovascular disease. The industry has been under increasing scrutiny by regulators, the public, and politicians, and some of this added scrutiny is at least in part due to bad behavior by certain companies but also due to heightened public and patient undue anger. Drug companies have become the boogie man, the bad guy. Apparently forgotten or pushed to the side is that these companies provide the lifeblood for patients. Some companies have had significant trouble. Roche announced leaving HIV but they are still supporting saquinavir use in the field and Fuzeon is still being used but less. They turned to devoting their assets to developing HCV drug development. GSK has had difficulties with AZT and abacavir but are developing a new integrase inhibitor. Abbott had much success with Kaletra but have also turned to HCV drug development. Many drug companies are thankfully devoting much effort to developing HCV drugs. So, where will our new HIV drugs come from? Will we see new HIV drugs? Will biotech companies devote their efforts to identifying and developing new classes of HIV drugs, will academic and government researchers do this? There are lot of people in this field who share my concerns that new HIV drug development is a problem.Faster drug approvals jeopardise patient safety, researcher claims

04 December 2008

www.pharmatimes.comThere are concerns that pressures on regulators to approve new drugs more quickly have reduced the focus on patient safety, and this problem is exacerbated by new efficiencies in drug marketing which can quickly expose large numbers of patients to unknown risks, warns a researcher writing in this week?s British Medical Journal (BMJ).

New medicines which receive approval by the US Food and Drug Administration (FDA) up to two months before the deadline set for a decision are more likely to be subsequently withdrawn from the market on safety grounds or to have to carry safety warnings, writes Kao, fellow in cardiovascular medicine at the University of Colorado Health Sciences Center, USA in the current BMJ (BMJ 2008;337;a2591).

For example, he says, it is estimated that 20 million patients were prescribed Merck & Co?s non-steroidal anti-inflammatory drug (NSAID) Vioxx (rofecoxib) over five years before it was taken off the market, and events attributable to the drug ´may number in tens to hundreds of thousands.¡

Dr Kao points out that, as a result of the US Prescription Drug User Fee Act (PDUFA), FDA approval times for new drugs more than halved, from an average of 33.6 months during 1979-86 to 16 months by 1992-2007. Moreover, regulators in the USA, European Union (EU) and UK are ´somewhat dependent on the industry for funding,¡ given that user fees account for 43% of the FDA?s drug oversight budget, 75% of European Medicines Agency (EMEA)?s funding and 100% of that for the UK?s Medicines and Healthcare products Regulatory Agency (MHRA), he says.

At the same time, drugmakers? marketing techniques are now so sophisticated that a new product can be released onto websites within 90 minutes of being granted approval, says Dr Kao, and he calls for these techniques to be used to improve post-marketing surveillance and adverse drug reaction reporting.

However, industry and regulators have been quick to deny that faster approvals are creating risks for patients. Ken , senior vice president at the Pharmaceutical Research and Manufacturers of America (PhRMA), said that Dr Kao?s paper ´suffers from a number of flawed assumptions, among the most glaring that FDA deadlines for approving drugs have shifted the agency?s focus away from patient safety.¡

´While PDUFA does carry timeframes for the completion of a review, the FDA can, and repeatedly has, returned to the sponsor with further questions about safety or efficacy that ultimately lengthen the review time. The fact remains that experts? analysis - including a paper published in 2007 by the New England Journal of Medicine - showed no increase in the overall rate of safety recalls after the user-fee system was introduced¡ said Mr .

Moreover, he added, it is ´erroneous to conclude that marketing plays a dominant influence on which medicines physicians to prescribe.¡ A survey this year of 501 physicians conducted by KRC Research found that peer-reviewed journal articles and information received from peers had more influence on physician prescribing decisions than industry marketing. ´What?s more, only 8% of physicians usually prescribed a brand-name medicine, while 41% of doctors surveyed usually prescribed generic drugs,¡ said Mr .

Before any new drug is approved, it will receive ´a very thorough review of its quality, safety and efficacy conducted by an appropriate regulatory agency,¡ adds a statement from the MHRA reported by the Press Association. In addition, the Agency notes that, ´in the UK, new drugs will also be reviewed by the UK?s Commission for Human Medicines. Usually there will be questions posed to the applicant during the review, and only when the appropriate regulatory agency is satisfied that any significant issues are resolved, will approval be given. At the time of approval, the company will have an agreed risk management plan in place to ensure continued safety monitoring of the drug in clinical use in the market place.¡