Viagra Still Riding High, But Competition Looms
June 12, 1998
Marketletter via NewsEdge Corporation : Pfizer's phosphodiesterase V inhibitor Viagra (sildenafil) remains the only orally-active drug for male erectile dysfunction and, as the first alternative to invasive or semi-invasive drug therapy, has broken all previous records for initial sales in the USA (Marketletter May 25).
The phenomenal success of the drug is likely to be enhanced by new data presented at the American Urological Association meeting held in San Diego earlier this month, which showed that the drug is effective even in men with the most severe impotence, ie those who can not get even a partial erection.
The new data, compiled from 10 other trials of the drug in the USA and Europe, found that 48% of men who never or almost never got an erection were able to achieve success with Viagra. The trials also show that the success rate in men with mild-to-moderate erectile dysfunction is around 70%.
However, claims that Viagra is being abused to increase sexual performance, rather than treat erectile dysfunction, has made it a controversial product, with the Israeli government only recently rescinding its ban on the drug (page 17). This view was encouraged by the AUA's decision to eject a company called University Compounding Pharmacy for selling it on the convention floor to delegates.
Nevertheless, the interest surrounding Viagra has led to a dramatic increase in attendance at the AUA. Over 17,000 delegates went to this year's meeting, compared to around 13,000 last year. Interest was also heightened by the prospect of near-term competition to Viagra, as well as a series of products further back in development which could expand the treatment options still further.
Two of the new orally-active agents - Zonagen's Vasomax (phentolamine) and TAP Holdings' apomorphine - have clinical data which suggest they offer a faster onset of action than Viagra, which takes 30-45 minutes to kick in. However, neither of these drugs appears to be as effective as the Pfizer compound in terms of response rates, although clearly no direct comparison can be made in the absence of head-to-head studies.
The tone of the conference was that the new agents will likely be niche players, representing no real threat to Viagra's blockbuster potential. This does not appear to have been dented even by a "mini-backlash" following reports of, at the last count, 16 deaths in men taking the drug (Marketletter June 1). The deaths are being investigated by the US Food and Drug Administration although no cause and effect relationship has been shown, and the agency said in a statement recently that the deaths "do not change FDA's perspectives on the safety of the drug." However, recent figures from IMS America suggest that the sales momentum for Viagra is slowing down.
The fact that some of the new agents act via different mechanisms to sildenafil (which prevents the enzymatic breakdown of cyclic GMP, allowing it to accumulate and increase signalling to boost blood flow), raises the possibility that combination therapy may be useful in the 30% of men who do not respond to Viagra alone, or cannot take it because they are on nitrates for cardiovascular disease.
Vasomax Data Reported Final data from two pivotal studies of Vasomax, a new formulation of an old alpha adrenergic antagonist, were presented for the first time at the conference. The two studies, Zon 300 and Zon 301, formed the basis of Zonagen's New Drug Application for Vasomax.
The final results of these studies, which were presented in a preliminary form last year (Marketletter June 2, 1997), were revealed by Irwin Goldstein of Boston University School of Medicine in a poster. At doses of 40mg and 80mg respectively, 51% and 53% of patients on the drug who had mild-to-moderate impotence - achieved penetration on 75% of attempts, compared to 38% of men receiving placebo. Erectile function, as measured by the erectile function domain of the International Index of Erectile Function, was corrected or improved to a less severe category of dysfunction in 40% of patients on the 40mg dose and 53% of those on 80mg. Improvements occurred in 15% of placebo patients.
Despite showing efficacy, the results have not been well-received by some analysts. The presentation of the results sparked a decline in Zonagen's share price as the markets decided that the data were not very positive and will make it difficult for the drug to make an impression on Viagra. Steve Lisi of Mehta Partners said the studies have only assessed patients with milder forms of impotence that can be hard for doctors to identify. He was also concerned about the high placebo response rate.
Others are less pessimistic, and Matt Geller of CIBC Oppenheimer maintains that Vasomax is the most important oral drug in the offing after Viagra, and could carve out a significant slice of the sizeable market for these agents if it reaches the market, eg in Viagra non-responders and those taking nitrates. A launch could occur as early as next year in the USA and, if approved, will be marketed by Zonagen's marketing partner Schering-Plough. It was approved in its first market, Mexico, earlier this month.
TAP's Apomorphine Considerable interest was generated by a new drug from TAP Holdings, the joint venture between Takeda Chemical Industries of Japan and Abbott Laboratories in the USA. Apomorphine acts in the central nervous system and has a dopamine-like action on brain functions responsible for erections.
As suggested by its central activity, apomorphine is effective primarily in men whose impotence is caused by psychogenic factors, estimated to make up 30%- 40% of the total patient population. A 457-patient study was presented at the AUA by Harin Padma-Nathan of the University of Southern California Medical School and showed that the drug, which is given sublingually, was effective between 45% and 60% of the time, depending on the dose taken (up to 6mg). However, the placebo response rate was also high at 34%. At its most effective doses, apomorphine was associated with mild nausea in up to 20%-30% of patients, although Dr Padma-Nathan said this tended to subside over time. TAP says it plans to file for approval of the drug, which is already marketed for other indications, as a treatment for impotence in 1999.
Vivus' MUSE One company that suffered at the AUA meeting was Vivus, which has developed an intraurethral formulation of an established treatment for erectile dysfunction, alprostadil, and is already marketing it along with partner Astra. Favorable data was presented on the long-term safety of the product, called MUSE, but most attention centered on a study conducted by researchers at the Presbyterian Hospital in Dallas, USA, which found that only 27% of patients achieved rigidity sufficient for intercourse with the product. Clinical trials conducted in support of its approval had found a 66% success rate.
The study, presented by urologist Pat Fulgham, also found a 41% rate of penile pain and burning in MUSE patients, and just 18% of the 115 men in the study chose to renew their prescriptions.
Vivus shares dropped on the back of media articles pointing to these " disappointing" results, although they bounced back after the company put out a statement noting that many of the patients in the trial had not received the drug at the approved recommended doses. Nevertheless, latest sales figures for the product from IMS America, according to the Wall Street Journal, have suggested that turnover of the product is declining in the face of competition from Viagra.
Further back in development is a drug in the same class as Viagra, ICOS' IC351, which may offer greater specificity and a lower tendency to cause side effects. Viagra has been associated with headache, flushing and dyspepsia as well as transient visual disturbances, including color-tinged or blurred vision. IC351 may avoid some of these reactions, but there is no clinical evidence for this as yet. The drug is in Phase II clinical trials.
Topical Agents Also highlighted at the AUA were new topically-applied products which are user-friendly and avoid the need for systemic treatment. Dr Goldstein reported the results of 114-patient study conducted at Boston University using MacroChem's Topiglan, which achieved response rates of 80%-90% with no significant side effects. The product is comprised of alprostadil and SEPA, a patented drug delivery technology which permits the drug to be absorbed through the surface of the skin. Dr Goldstein said that he believes the gel will give Viagra "fierce competition" once it is on the market. MacroChem says it is now gearing up to begin negotiations with potential licensing partners for the product.
Meanwhile, another topical alprostadil product, NexMed's Alprox-TD incorporating the company's proprietary NexACT absorption enhancer, can achieve increases in blood flow to the penis equivalent to that seen with injectable alprostadil, according to a study presented at the AUA. A Phase I trial of the drug has been completed in the USA, and Phase II studies in both men and women are ongoing. NexMed has signed distribution and license agreements for the Taiwan, Uruguay, and Argentine markets, although the product is not yet available in any of these countries.
Injectables Not Dead? Finally, Senetek presented results of a survey which indicated that 86% of users were happy with its developmental Invicorp (vasoactive intestinal peptide plus phentolamine) product, which offers an 83% response rate according to clinical trials, despite it being an injectable. "After the dust settles from the euphoria over the new oral therapies, the world will inevitably come to know Invicorp as the gold-standard [and] as the leading second-line therapy after pills," said chief executive Anthony Cataldo.
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