The following information comes from a variety of sources.
Vivus is the pioneer of a new therapy for erectile dysfunction. MUSE, or Medicated Urethral System for Erection, uses a small plastic device to place a small gelatin pellet into the urethra. The onset of response is consistently rapid regardless of dosage. In clinical trials, the onset of erection began approxiamtely 7.3 minutes after administration. Maximal penile engorgement occurred at approxiamtely 21 to 23.5 minutes.
According to Vivus officials, impotence affects between 15 and 20 million men in the U.S. and an additional 50 million worldwide. These numbers will continue to grow as the male population ages. According to the Massachusetts Male Aging Study from the American Journal of Urology, over 24 million men suffer from moderate or complete impotence now, and that number will increase to 28 million by the year 2005.
MUSE is the largest first year product ever launched in urology, and probably the second biggest ever behind only prostate cancer drug Lupron Depot. Nearly 500,000 patients sought treatment in the first year, as sales of the product exceeded $100 million in the first 3 quarters after the launch, making it one of the fastest selling pharmaceuticals ever. These sales came with no advertising, and just from demand in the US marketplace. Vivus finished 1997 with an EPS of $1.03. Sales for the year come in at just under $129 million and with margins of 70%, making the drugs's profitability attractive.
VVUS officials state that 50% of men with COMPLETE erectile dysfunction are able to return to sexual intercourse after using the product.
Two identically designed phase III studies (94-01, 94-02), referred to collectively as the Evaluation of Alprostadil for Safety and Efficacy (EASE) study, were conducted by 58 centers across the United States. After a double-blind titration phase in the clinic to determine the dosage producing an erection sufficient for intercourse or a rigid erection, patients were randomly assigned to alprostadil at that dosage or placebo for 3 months
EASE study data provide the most compelling evidence for the efficacy of MUSE, because of the large number of patients who completed the study and the large percentage who achieved sexual intercourse.
In two identical multicenter, double-blind, placebo-controlled studies, 1511 patients with erectile dysfunction were randomized to receive MUSE or placebo at home for 3 months. The mean duration of erectile dysfunction was 4 years, and each participant had at least a 3-month history of inability to attain an erection without medical assistance. Patients participating in the study began dose titration in the clinic with doses between 125 and 1000 mcg. A total of 996 patients (66%) achieved an erection sufficient for intercourse. Not all patients participating in dose titration tolerated MUSE, primarily because of penile pain. Despite a history of chronic erectile dysfunction, 64.9% of patients in the MUSE group had sexual intercourse at least once. In contrast, only 18.6% of patients receiving placebo had sexual intercourse (P<0.001). Among the patients reporting sexual intercourse on MUSE, a mean of 7 of 10 systems resulted in intercourse.34,41 The rate of orgasm was higher in the MUSE group as well (63.4% vs 23.6%, P<0.001).41
Despite chronic erectile dysfunction for an average of more than 4 years, 64.9% of patients had sexual intercourse at least once with MUSE during home treatment vs only 18.6% with placebo.
Efficacy was consistently maintained throughout the 3-month observation period, as 66.4%, 69%, and 73.5% of administrations resulted in sexual intercourse in responders during the first, second, and third months, respectively. Furthermore, the percentage of responders who achieved sexual intercourse increased from 67.6% after the first administration to 92% by the fourth administration. This success rate demonstrates that patient responsiveness to home treatment can be determined by the first few administrations.
Patients receiving MUSE had high comfort levels at all dosages. In the EASE study, at least 88% of patients rated MUSE as very comfortable, comfortable, or neutral at each dosage (Figure 12).34
About the patients:
All patients were men unable to achieve or maintain erections sufficient for sexual intercourse for at least 3 months before study entry. Mean patient age was 61.5 years (range: 27 to 84 years in individual patients). The mean duration of self-reported erectile dysfunction was 45.8 months (range: 29 to 55 months in individual studies). The distribution of patients according to etiology of erectile dysfunction was generally consistent across studies. Erectile dysfunction was primarily attributable to vascular insufficiency in 31.9% of patients, surgery or trauma in 31.2%, diabetes mellitus in 16.4%, and other reasons in 20.4%.
ETIOLOGY OF ERECTILE DYSFUNCTION:
Diabetes mellitus and vascular disease are two of the most common disorders associated with erectile dysfunction.
Although erectile dysfunction is no longer considered a necessary consequence of the normal aging process, the actual cause is not always easy to determine. Because of the complex nature of human sexual response and penile physiology, erectile dysfunction can have many different causes. In addition, while the causal factors are generally characterized as psychogenic, hormonal, neurogenic, arterial, or cavernosal, erectile dysfunction often results from problems in more than one of these areas.2 For example, the most common systemic disorder associated with erectile dysfunction, diabetes mellitus, is a hormonal disorder that may cause both vascular and neurologic deficiency. Five to 10 years ago, it was thought that most cases of erectile dysfunction were primarily psychogenic; however, it is now known that most cases have an organic component.
While there is an increased recognition of the importance of organic causes, which are thought to be involved in about 80% of cases of erectile dysfunction, it is assumed by many that psychological factors may contribute to 20% of cases. Psychogenic erectile dysfunction can be related to anxiety, depression, tension, guilt, stress, and marital discord.
Doses available: price to wholesaler: suggested pricing:
125 mcg 94.80 118.50
250 mcg 99.30 124.13
500 mcg 106.20 132.75
1000 mcg 114.60 143.25
Side Effects and Contraindications:
The most serious local side effects in clinical trials were priapism (rigid erection lasting more than 6 hours) and prolonged erection (rigid erection lasting more than 4 hours and under 6 hours), reported by <0.1% and 0.3% of patients, respectively. Although infrequent, these events are a potential risk of pharmacologic therapy. Physicians should lower the dose or consider discontinuing MUSE treatment in any patient who develops priapism or prolonged erection.1
The most frequently reported side effect in clinical trials was mild-to-moderate penile pain, reported at least once by 36% and 32% of patients, during in-clinic titration and home treatment, respectively.1 In patients reporting penile pain, not every administration was associated with it. Of 4,961 doses administered at home, 11% were pain-related.2 Urethral pain was reported at least once by 12% of patients during home treatment.1
Vaginal burning/itching was reported by 5.8% of partners of patients using MUSE. It is unknown whether this effect was due to MUSE or a result of resuming sexual intercourse.1
MUSE is contraindicated in men with hypersensitivity to alprostadil, with abnormal penile anatomy, with conditions that predispose to priapism, and in whom sexual activity is inadvisable. MUSE should not be used for sexual intercourse with a pregnant woman unless the couple uses a condom barrier.
OVERVIEW OF STUDY DESIGNS
A comprehensive series of studies of MUSE that included seven double-blind, placebo-controlled trials of more than 2500 couples was conducted to determine its clinical profile (Figure 11).34 More than 30,000 MUSE systems were administered, for a total of more than 500 patient-years of treatment. Five hundred patients received MUSE therapy for more than 6 months; some were followed on long-term therapy for more than 3 years.
According to the trials, Muse was effective, regardless of the duration of the ED.
"MUSE was as effective in men with a 1-year history of erectile dysfunction as it was in men with erectile dysfunction for at least 6 years, and previous therapy for erectile dysfunction did not affect outcome."
Demographics should increase interest in erectile dysfunction. LIke other disease, erectile dysfunction is more likely as a man ages. As the baby boomers age, there is a huge new influx of patients with erectile dysfunction coming into the doctor's office and the marketplace. And these new Baby Boomers aren't likely to go quietly on with their lives with ED. They are more like to go out and look for reasons and answers to their problems.
VVUS officials are also counting on the fact that the vascular damage that lies behind erectile dysfunction ia a degenerative disease. Even if patients are well-served by oral medications now, they likely won't be in ten years. If VVUS doesn't get them at 50 years old, they'll get them at 60. And since the biggest marketing challenge is attracting patients to seek treatment, even if Pfizer takes some of the market soon after Viagra's launch, that alone would help VVUS long term in its marketing efforts if, in the process, they bring in lots more patients into the physician's office.
VVUS officials contend erectile dysfunction is a "couple's disease"
Leland Wilson: "Typically, the wife is the instigator, bringing the husband in for therapy. He's usually reluctant until he goes for treatment, then becomesa willing participant when he sees what's available"
74% of prescriptions written for MUSE are reimbursed by insurers, and the productr is covered by every major pharmacy benefit manager.
VVUS has set up a hot-line to answer patients questions. In the first three months VVUS was getting 800 to 1000 calls per day.
Of all the potential competitors, Pfizer, which filed an expedited NDA last September, represents the most imminent competitive challenge to VVUS. Even
Schering-Plough is likely to be a year or more from market, given that it hasn't even filed its NDA yet.
VVUS officials argue that the systemic approach to treatment isn't the best way to deliver a drug because so little blood actually flows into the penis. In fact, injection therapy is the best system- its just not very appealing to men. MUSE offers easy application and direct delivery.
VVUS officials believe that oral medicaitions will help expand the market by making new treatments more widely known, while proving effective for only a segment of the population--those psychogenic or mildly dysfunctional who don't suffer from a complete inability to have sexual intercourse.
Patients in VVUS clinical trials had to have failed to get an erection sufficient for sexual intercourse for three months prior to the trial. the average length of time that patients suffered from erectile dysfunction in the VVUS trials was four years.
By contrast, patients in clinical trials for the oral medicaition had to have been diagnosed with erectile dysfunction, but had to be able to have sexual intercourse at least once during the lead-in to the clinical trials.
John Richard, VP of corporate development argues that "Pfizers and schering-plough's entrance into the market is the best thing that could happpen to VVUS, if only for the consumer marketing muscle they bring. They know how to get consumer's into the physician's office and that continues to be the biggest challenge in this (erectile dysfunction) market"
The issue isn't which ED product the patient will use, but rather whether he's willing to seek treatment in the first place. As a result, new competitor's tend to expand the market rather then take away existing market share.
For example, MUSE became the market leader with virtually no canibalization of the existing injection therapies.Both VVUS and Pharmacia Upjohn expected the latter to take a hit when MUSE came to market. Bbut what happened instead is that new patients were created.
John Gangolli, VP of Sales and Marketing, argues that its ridiculous to think that the ED marketplace will be gobbled up by a single company or that the advent of a new competitor will seriously threaten VVUS' existing position. "I've seen alot of product launches and it almost never happens that a new drug coming into the marketplace completely wipes out a product already there"
John Richard argues that "over time there will be segmentation (of the ED market)
and in every category there will be patients for whom one product works and others don't."
In particular, VVUS officials believe that oral medications are likely to have broader but shallower market reach, better serving patients with milder forms, while leaving VVUS those patients suffering from more severe cases.
VVUS started its US launch with 50 reps to call on the 7,700 urologists in the country. Over the past year, they've added an additional 24 reps to expand their coverage to 11,000 physicians in other specialties, such as diabetes, cardiovascular, and endocrinology, who in the course of their practice find patients duffereing from erectile dysfunctioon. And the company plans to add even more reps this year.
Vivus plans to work closely with key specialist groups--physicians to whom it can make the case about the greater effectiveness of local delivery over systemic drugs--and expand their sales force as teh market grows. Vivus is betting that even if its large competitors take the product to general practitioners, not all of those practitioners will write scripts themselves--many will instead refer patients to the urologists, diabetologists, and other specialists Vivus's 75-person sales force can call on effectively. Vivus may supplement with contract reps, but, the company believes, even GP's can be segmented, with high-prescribing GPs representing a smaller group that can be effectively targeted through organic sales force growth.
In Europe, by contrast, Vivus's strategy is strikingly different. Last year, the company signed a highly innovative agreement with one of Europe's leading pharmaceutical marketing organizations, Astra AB, to quickly get MUSE into the European marketplace.
Under terms of the deal, Astra commited to pay up to $30 million in up front payments, based upon regulatory miletstones, and to create, train, and launch adedicated sales force to detail Muse in the top five European markets. More importantly, the agreement gives Vivus the option to take over the sales force at the end of five years, two years before the patent expires, in the territories it chooses in those five markets. "The plan is to use those sales forces as a stepping stone into the European market," says Leland Wilson. "We hope eventually to bring in other products and expand to other markets to create a full-fledged marketing organization throughout the world."
For Astra, whose marketing skill is unquestioned, but whose short-term pipeline is lacking, the deal clearly brings benefits in access to a product that is widely believed to have blockbuster potential over the next five years. Still, by all measures, the deal seems a particularly good one for Vivus which, after five years, will get a sales force that as Wilson notes "will be as good as, if not better, than anything we could develop ourselves," without paying a dime for it.
One other reason Vivus could get such favorable terms is that the company actually had several large European drug firms vying for the rights to launch Muse in what Wilson calls "a very competitive situatoin in deal negotiations."
Vivus has also licensed marketing rights to Muse to Janssen Pharmaceutica in a number of smaller and developing markets, including Canada, Mexico, Africa, Russia, the Middle East, and some Asian markets, including China.
The company expects between 15 and 20 countries will grant regulatory approval to its product during 1998.
The Astra press release on its launching of the MUSE product:
Marketletter
Marketletter Publications Ltd. (UK)) Information
Access Company.
Monday, February 23, 1998
UK Launch Of Astra's MUSE
Subscription: 449 British Pound Sterling per year as of 1/97. Published weekly. Contact Marketletter (Publications) Ltd., 54/55 Wilton Rd., London SW1V 1DE, UK.
Astra Pharmaceuticals has launched its transurethral product for the
treatment of male erectile dysfunction of primarily organic etiology,
MUSE (alprostadil), a synthetic form of the vasodilator prostaglandin
E1, in the UK. It was launched in its first market, the USA, in January
last year. A Phase III clinical trial of MUSE, which is licensed from
VIVUS Pharmaceuticals, demonstrated that it was effective in 65.9% of
patients in the clinic, while 64.9% of men in the home treatment phase
achieved intercourse at least once versus 18.6% of placebo receivers.
The recommended starting dose of MUSE is 250mcg, which must be titrated
under medical supervision until the correct dose is found, following
which the patient can use the product at home. Only two doses are
recommended in every 24-hour period. The cost to the National Health
Service for a pack of six MUSE will be L54.84 ($89.37; 125mcg), L59.70
(250mcg and 500mcg) and L61.08 (1,000mcg). It was noted at an Astra
press meeting that there needs to be a shift towards the general
practitioner treating patients with erectile dysfunction. However, John
Pryor, a consultant and urologist, pointed out that the cost of MUSE
"is probably an issue," despite the fact that the treatment has a
significant effect on quality of life and that in practice patients are
quite reasonable with their demand for the product. He also noted that
approximately 7% of men regain spontaneous erection following treatment.
Astra is also the license holder for the rest of Europe, Australia, New
Zealand and South America.
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More recently, Vivus's stock slide has been tied to specific problems. The company's early success led to production shortfalls which hit the company hard in the fourth quarter of 1997. "We've exceeded every expectation we had," says Wilson. "And that put tremendous pressure on the operations group to put out product." Running three shifts a day, six days a week, out of Vivus's small New Jersey manufacturing facility finally caught up just as the company was bring on-line a new manufacturing facility. "We were just spread too thin," he acknowledges. "We couldn't continue to produce at the rate we had been."
Vivus officials don't disguise how frustrating the problem has been. Three months into one of the most successful product launches ever, notes Julian Gangolli, "we had to take our foot off the accelerator." He recalls that some pharmaceutical executives argued that having to cut back on marketing because of too much demand was being generated is a "nice problem to have." "Well," he goes on, "it was a lousy problem to have. We've spent an inordinate amount of time trying to get product from one place to another just to satisfy customer demand. We also spent a lot of time handling dissatisfaction from customers because they couldn't get the product."
Vivus is already looking for new products to expand the company's base. These new products are most likely to come in areas realted to erectile dysfunction and transurethral delivery. Vivus is already developing a second treatment for ED, called Alibra, which will present a different safety and efficacy profile and thus treat patients for whom Muse doesn't work.
EPS estimates from Stock Smart:
high low mean #of brokers
1998 1.05 0.46 0.74 6
1999 5.51 1.46 2.91 3
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I was going to comment on PFE and Viagra, but its hard to judge this drug, when so substantially little information has been released to date by the company itself. So instead, i'll just give a little background on the estimated <overestimated,IMO> market size for their product, and the study questions used to determine this market size:
Sex Quiz for Men
How science uncovered an impotence "epidemic"
From recent reports on impotence, you'd think it was spreading like the flu. In fact, what qualifies as erectile dysfunction (ED), as doctors call it, has changed. It used to mean being unable to sustain an erection during intercourse. But many experts felt this overemphasized mechanics--there's more to sexuality than plumbing, after all. So a groundbreaking study published in 1994 expanded the meaning, asking men nine questions about their sexual vigor. A selection:
How satisfied are you with your sex life?
How satisfied are you with your sexual relationship with your present partner or partners?
How satisfied do you think your partner(s) is (are) with your sexual relationship?
Has the frequency of your sexual activity with a partner been:
0.as much as you desire? a.less than you desire? b.more than you desire?
If your answers add up to "dissatisfied," you may qualify as suffering from ED. You would not be alone. Media reports now regularly state that 20 million to 30 million men in the U.S., and perhaps 140 million worldwide, have trouble achieving erections--and only 5% get treated. To developers of ED pills, such numbers are extremely sexy.
The statistics have gone on to provide foundation for analysts' bullish market
reports. Just crunch a few numbers yourself: Say an erection-boosting pill would be taken two times a week by a typical man with ED, roughly 100 doses a year. Say it's priced at $10 a dose--a reasonable buy for one of the best things in life. Assume just one in five men with ED uses it. Ca-ching! Annual U.S. sales of more than $4 billion. Here is how analyst David Saks of Gruntal & Co., quoted by Reuters, sized up the potential for Pfizer's Viagra pill for ED: "I hereby make the outrageous claim that Viagra will become the world's biggest drug success story, bigger than anything that has ever been seen." Added Viren Mehta of Mehta & Isaly on Viagra's potential: "Any number is possible." Among the ideas that excited some analysts was the possibility that millions of men and women with no medical need for the new drugs would take them to enhance sex, vastly amplifying sales. (Women also have erectile tissues.)
So, if the mild ED market is over-inflated, and Viagra is a drug targeting mild ED cases.......................well, you get my point.
regards,
Mike |
