Replies to post #44440 on Biotech Values

[DewDiligence]

Re: Sculptra

The product seems to fit into a no-man’s land (actually a no-woman’s land, since the overwhelming majority of dermal-filler patients are female) between Restylane/Juvederm and ArteFill. I don’t think it will succeed in the cosmetic arena where patients have to pay their own way.

>Just finished my first Artecol injections… Eventually he agreed to let me inject the patient free of charge as a trial, but I'm leary at this point and don't see myself using it again.<

I hope you remembered to send in your malpractice premium :-)

p.s. I assume you mean ArteFill rather than ArteColl. The latter is not being marketed in the U.S.

[DewDiligence]

FDA approves Perlane, a “heavy duty” version of
Restylane. Good news for MRX; bad for AGN.

http://online.wsj.com/article/SB117814432873790004.html

>>
FDA Approves Wrinkle Drug

By RHONDA L. RUNDLE
May 2, 2007 6:33 p.m.

Medicis Pharmaceutical Corp. said it received Food and Drug Administration clearance to sell Perlane, an injectable anti-wrinkle gel that is a thicker formulation of its Restylane dermal filler.

The approval gives the Scottsdale, Ariz., dermatology company a second product in the fast-growing market for non-surgical facial rejuvenation. The move will help Medicis meet mounting competition from Irvine, Calif.-based Allergan Inc., a larger company that sells two versions of a filler called Juvederm. Medicis said it would start shipping Perlane to dermatologists, plastic surgeons and other specialists within days.

Perlane, like Restylane and Juvederm, is a hyaluronic acid that is a natural, biocompatible substance. The products are approved as medical devices for use to plump up the deep folds that run from the bottom of the nose to the corners of the mouth. Physicians are using fillers in parts of the aging face that loses natural volume.

Perlane is identical to Restylane, except the gel particles are bigger, said Jeffrey S. Dover, a Boston dermatologist and investigator on the Medicis FDA human test. "The amount of material needed was slightly less than with Restylane, but the difference wasn't statistically significant," he added. Perlane persisted at least six months in two-thirds of patients, about the same as Restylane, he said.

Some physicians in Canada have been using Perlane and Restylane in combination to get optimal results in older patients who need significant volume restoration in the lower face. "It's great to attack the problem in layers," says Arthur Swift, a plastic surgeon in Montreal. Perlane is the "mattress stuffing" and Restylane is the "sheet tightening" on top, he said.
<<

[DewDiligence]

(SNY MRX AGN JNJ BFRM) FDA Approves Sculptra for Cosmetic Use

[SNY’s Sculptra was previously approved by the FDA only for lipoatrophy (facial wasting) in people with AIDS. With approval for cosmetic use generally, Sculptra joins an array of dermal fillers that includes Restylane and Perlane from MRX, Juvederm from AGN, Prevelle Silk from JNJ, and Radiesse from BFRM.

These products are not fungible, however; rather, they form a continuum from firmer and longer-lasting to softer and shorter-lasting. In general, the firmer and longer-lasting products are more painful during the injection procedure and are not as natural-looking as the softer and shorter-acting products. From the firm and long-lasting end of the spectrum to the soft and short-acting end of the spectrum, I would order the products as follows: Sculptra, Radiesse, Perlane, Restylane, Juvederm, Prevelle Silk. Sculptra consists of a polymer from the alpha-hydroxy-acid family; Radiesse consists of calcium hydroxylapatite (a component of bones and teeth); and the other products in the above list consist of hyaluronic acid in varying degrees of viscosity.

In the US, Restylane/Perlane has the leading market share, Juvederm is second, Radiesse is a distant third, Prevelle Silk (which JNJ acquired from Mentor) is fourth, and Sculptra is not yet on the radar screen of most derms and plastic surgeons.]

http://finance.yahoo.com/news/FDA-Approves-prnews-1450097164.html?x=0&.v=1

›Wednesday July 29, 2009, 12:00 pm EDT

BRIDGEWATER, N.J., July 29 /PRNewswire-FirstCall/ -- Sanofi-aventis U.S. announced today that the U.S. Food and Drug Administration (FDA) approved Sculptra®Aesthetic (injectable poly-L-lactic acid) for the correction of shallow to deep nasolabial fold (smile lines) contour deficiencies and other facial wrinkles which are treated with the appropriate injection technique in healthy patients. Sculptra®Aesthetic works gradually to offer natural-looking results that can last up to two years.

"We are excited by the FDA approval of Sculptra®Aesthetic because it changes the landscape of what physicians can offer patients seeking natural and gradual looking results from an aesthetic injectable that is long-lasting," said Doris Day, M.D., Clinical Assistant Professor of Dermatology at New York University and in private practice in New York City. "Sculptra®Aesthetic allows for a natural correction."

The FDA approval of Sculptra®Aesthetic is based on results from a randomized, comparative, evaluator-blinded, parallel group, multi-center study of 233 patients. Patients received Sculptra®Aesthetic or an approved human derived collagen for the treatment of their nasolabial fold wrinkles.

Sculptra®Aesthetic was administered in a single treatment regimen, at three week intervals, for up to 4 treatment sessions for the correction of shallow to deep nasolabial fold contour deficiencies using a deep dermal grid pattern (cross-hatch) injection technique. The Sculptra®Aesthetic patients were followed for an additional 12 months. Sculptra®Aesthetic treatment effects were maintained up to 25 months after the last treatment session, while the human derived collagen was effective up to 3 months.

"Sculptra®Aesthetic showed effective correction of the nasolabial folds, which are considered to be the hallmark signs of facial aging," said Paul Chew, M.D., Chief Science Officer/Chief Medical Officer, sanofi-aventis U.S.

No serious adverse events were reported in this study for either treatment. Commonly occurring short-term injection site reactions were bleeding, tenderness or pain/discomfort, redness, bruising, itching or swelling and were reported in both treatment groups. Other adverse events reported during the 25 month trial included small bumps and lumps, some with a delayed onset and were mild or moderate in intensity. Most side effects resolved on their own; one small lump required treatment by the healthcare provider.‹

[DewDiligence]

Sanofi’s Sculptra Needs a Dose of Patience

[Now that it has an FDA label for cosmetic use (#msg-40115547), is Sanofi-aventis’ Sculptra a serious contender to take share in the dermal-filler market from Restylane and Perlane (MRX), Juvederm (AGN), Radiesse (BFRM), and Prevelle Silk (JNJ)? These products form a continuum from firmer and longer-lasting to softer and shorter-lasting. In general, the firmer and longer-lasting products are more painful during the injection procedure and are not as natural looking as the softer and shorter-acting products. From the firm and long-lasting end of the spectrum to the soft and short-acting end of the spectrum, I would order the products as follows: Sculptra, Radiesse, Perlane, Restylane, Juvederm, Prevelle Silk. Sculptra consists of a polymer from the alpha-hydroxy-acid family; Radiesse consists of calcium hydroxylapatite (a component of bones and teeth); and the other products in the above list consist of hyaluronic acid in varying degrees of viscosity.

After reading this article in the NY Times, I’m more inclined than ever to think the answer to the question posed above is No. Sculptra seems to be overdesigned for the general cosmetic market (as opposed to the niche market of facial wasting in AIDS patients, where Sculptra is the only FDA-approved dermal filler). I think the risks inherent in Sculptra’s use, described in the article below, will cause many docs to be concerned about malpractice suits and be reluctant to recommend Sculptra for all but the most severe cases. Consequently, I don’t see Sculptra taking more than a mid-single-digit market share in the US cosmetic market.

If I’m wrong and Sculptra does in fact take a sizable market share, its share would presumably come at the expense of Radiesse. Hence, the commercial uptake of Sculptra is something that BFRM investors need to watch closely.]

http://www.nytimes.com/2009/09/24/fashion/24Skin.html

›By CATHERINE SAINT LOUIS
September 24, 2009

Sculptra, a long-lasting filler that has been used since 2004 to plump the cheeks of H.I.V.-positive patients with facial wasting, is finally having its cosmetic debut. In July, the Food and Drug Administration approved Sculptra Aesthetic — as the cosmetic version is named — for use to improve the appearance of nose-to-lip wrinkles (think Jack Nicholson’s Joker), horizontal chin wrinkles and so-called marionette lines that frame lips.

But that is not to say Sculptra is a new-to-the-ball debutante. Since 2004, Sculptra has been used off-label not only to tame stubborn skin folds but also to add volume to cheeks and temples withered by time. Now that Sculptra has been approved for some cosmetic uses, plastic surgeons and dermatologists are expecting a surge of interest. [Well, maybe. Keep reading and you may find you disagree.]

Previously, little prevented a dermatologist or plastic surgeon from recommending Sculptra to a patient gaunt from exercise or distressed by hollow cheeks. In fact, last year, plastic surgeons and other doctors treated nearly 80,000 patients with Sculptra, up from 46,732 in 2005, according to the American Society of Plastic Surgeons.

Sculptra has already won over some doctors and patients. One advantage is its longevity; it can last up to two years once an optimal result is achieved, while alternative fillers including Restylane, Juvéderm and Evolence generally last a year or less. [Oddly, the author neglects to mention Radiesse from BFRM.] Another advantage is Sculptra’s ability to address broader depressions like sunken cheeks.

That said, the drawbacks of Sculptra include the need for several treatments in some cases to achieve a desired result, the need to massage the treated area for up to a week, and the risk of developing lumps beneath the skin.

Dr. Z. Paul Lorenc, a plastic surgeon in Manhattan who offers eight kinds of fillers, thinks of Sculptra primarily as a “volumizing agent.” Fillers tackle wrinkles or depressions by discretely plumping up tissue, Dr. Lorenc said. Sculptra, he said, “diffusely increases the volume of the area I’m injecting.”

Made of a synthetic material called Poly-L-lactic acid, Sculptra is injected deep into the tissue below the skin to spur a patient’s collagen growth gradually. Results — sometimes months in the making — look natural, a benefit touted by Sanofi-Aventis U.S., the company that makes Sculptra.

“What we bring to the market is natural and gradual replacement of lost collagen,” said Brent Ragans, the vice president of general therapeutics at Sanofi-Aventis U.S. “If you look at it from a consumer standpoint, the ability to look better over time, without people looking like something has been done” is desired.

Collagen renewal takes patience. “This is not a lunch-time filler,” said Dr. Karol A. Gutowski, chief of plastic surgery at NorthShore University HealthSystem in Illinois. “You don’t come in and boom, you’re ready to go to your cocktail party the next day.”

Often, multiple treatments, spaced four to six weeks apart, are necessary. Some lucky people respond to a single treatment, but two or three is more typical, most doctors interviewed for this article said.

At a time when many anti-aging fillers offer immediate results, that wait-and-see period tested the patience of Dr. Kevin S. Pinski, a dermatologist in Chicago, and that of his patients. “It’s a little bit of a tough sell,” said Dr. Pinski, who injected Sculptra in patients for roughly two years and no longer does.

Cost, too, can be an issue. Dr. Pinski, who is on the advisory boards for filler marketers Allergan and Medicis, then charged $1,000 for each vial of Sculptra. That results would last up to two years “was pretty darn good,” he said, and worth the final bill for some patients.

Other doctors nationwide charge $800 to $1,200 per Sculptra vial. At Dr. Lorenc’s office, a vial of Sculptra is $1,200, while Restylane and Juvéderm are $750 a syringe.

Side effects of Sculptra include tenderness and redness near the injection site. But what has caused the most concern is the occasional occurrence of small bumps that can be felt under the skin. Some bumps are visible. Doctors speculate that they are un-dispersed Sculptra or a result of not injecting deep enough.

Massaging after injection helps evenly distribute the product, some say, as does massaging injection sites for five minutes five times daily for five days after treatment. Dr. Gerald N. Bock, a dermatologist in Stockton, Calif., was so concerned about nodules that he discontinued his use of Sculptra. In a recent interview, he said, it’s a “nice filler” for broad areas like hollow cheeks and temples, but “you can certainly do that with other fillers like Restylane, Radiesse or Juvéderm.” They just won’t last as long, he said.

In 2008, he called Sculptra a “time bomb” on his Web site because a few patients developed nodules, one 18 months after treatment. That blog post hasn’t stopped Sculptra representatives from wooing him. One once told him that several company representatives who received Sculptra treatments “have nodules they can feel but can’t see.”

Clinical trials found that 8.6 percent of patients who had been treated with Sculptra Aesthetic developed lumps. “That’s a bit high,” said Dr. Mark L. Jewell, a plastic surgeon in Eugene, Ore., and the organizer of the Physicians Coalition for Injectable Safety. “That to me is certainly higher than what I’ve seen with hyaluronic acid-type fillers.”

In a recent interview, Dr. Adriana Guana, the medical director for Sanofi-Aventis dermatology products, including Sculptra, emphasized that the patients who had complications were “still happy.” The lumps “were not bothersome, they were not serious, and they resolved spontaneously.”

But patients who are horrified by their Sculptra lumps are not hard to find; their stories of woe are hotly discussed on cosmetic enhancement sites like RealSelf.com and MakeMeHeal.com.

Several doctors said the solution for a lump is either to wait months or years till it goes away on its own, or, Dr. Lorenc said, “you can excise it, that’s the real answer.” In contrast, after injections with hyaluronic acid fillers, “if you get a lump or bump or whatever, it can be injected with hyaluronidase” to dissolve it, said Dr. Alan Gold, the past president of American Society of Aesthetic Plastic Surgery. A doctor’s skill matters when it comes to all anti-aging injectables, and that is especially true for Sculptra. Dr. Lisa M. Donofrio, a dermatologist with four offices, including one in Manhattan, said she is upfront with candidates for Sculptra. “I can put it safely in you,” Dr. Donofrio said she tells them. “After that, it’s up to how your body forms collagen around this product.” (Dr. Donofrio has been paid to consult for the marketers of rival fillers Medicis, and Allergan; in 2004, Sanofi-Aventis.)

What’s more, off-label usage can be problematic because doctors can’t be educated for such indications by the maker of the injectable. “The company can’t even mention off-label uses,” said Dr. Brian M. Kinney, a clinical assistant professor of plastic surgery at University of Southern California. “If something became too enthusiastically implemented without a critical enough eye, the chances of problems greatly increase and we are not serving our patients.”

Several years ago, before Sculptra was approved for cosmetic use in the United States, Dr. Kinney was trained by Sanofi-Aventis in Europe to use Sculptra for facial wasting in H.I.V. patients. But as Dr. Guana of Sanofi-Aventis said, “what happens after the training is the physician practice and their own judgment.” Dr. Kinney began injecting Sculptra at his practice in Los Angeles after his return, and taught other stateside doctors how to best inject for aesthetic enhancement.

But the trouble, as Dr. Kinney sees it, is that when off-label uses of an injectable are not openly discussed there is a “risk of not wide enough a dissemination of pros and cons.” As of late July, Sanofi-Aventis can offer robust training for cosmetic indications for doctors, but some don’t feel that will necessarily change the landscape.

In the coming months, Dr. Robert Singer, a plastic surgeon in San Diego, foresees “a lot more people using it who aren’t appropriate providers” and he fears an uptick in injectors using Sculptra Aesthetic in inappropriate areas like in the lips and under-eye depressions. “I don’t want to say it doesn’t have its place,” said Dr. Singer, who has not injected much Sculptra in his practice. “I have friends who use it and like it. I think it needs to be judiciously used and I’d be concerned in superficial areas.”‹