While Botox Cosmetic was the first, there are now many toxins in various stages of development. Since FDA approval of Dysport, the big question is how this new form of botulinum toxin will stand up to the titan of toxins. Recently, a new form of botulinum toxin, Dysport, became available in the marketplace. Given the fact that 203,000 hits on Google come up when searching “Dysport” as compared to 803,000 for “botulinum toxin,” this event has clearly been of great interest to the general public and media. But while the advent of this and other new forms of botulinum toxin has been highly anticipated, the big question in the minds of many — including this investigator — is whether they will be able to live up to the hype? What’s New The main new forms of botulinum toxin in Phase III clinical trials are PurTox (Mentor Corporation) and NT201 (Merz Pharmaceuticals). Additionally, there are other forms of toxins from China, Brazil and South Korea that are being tested in countries other than the United States. As Dysport was recently approved by the FDA, this discussion will focus upon the characteristics of this Medicis product in comparison to Allergen’s Botox Cosmetic. Dysport VS. Botox Characteristics Molecule Each botulinum toxin batch contains a slightly different molecule, so it is no surprise that the Dysport molecule isn’t exactly the same as the Botox molecule. On the other hand, the similarities between them are quite striking, with both molecules being in the 900 kilodalton size range, with a 150 KD subunit, the active toxin molecule, which is surrounded by non-toxin associated proteins, resulting in the 900 KD size. There are various subunits that make this configuration possible. Composition While Botox is prepared with human albumin in the vial, the Dysport vial contains both lactose and albumin. Both vials contain toxin-associated peptides. It is unlikely that the lactose in the Dysport vial will result in any problems for those who are lactose-intolerant due to the fact that lactose intolerance is specific for gastrointestinal enzymes and isn’t an allergy, per se. Strength While there have been no firm comparison trials for Botox versus Dysport, Dysport is supplied in vials of 300 units, which will be fairly equivalent to 100 units of Botox. Studies performed in Europe and the clinical trials in the United States on Dysport have shown a conversion ratio of 2.5:1 to be a good starting point, while a conversion rate of 4:1 typically results in higher rates of adverse reactions. With the use of a 300-unit vial, it appears that the material will be reconstituted in the same manner as Botox and will treat approximately the same number of patients or slightly more than a 100 unit vial of Botox (assuming a 2.5:1 conversion ratio). Time Available for Use While many studies have shown that reconstituted Botox retains activity for longer than the 4 hours noted in the package insert, that is the time of usage for Botox as per package insert (PI). Dysport has a PI time of use of 8 hours in the EU, yet a recent study by Doris Hexsel shows activity of Dysport 15 days after reconstitution.1 Time to Onset Time to onset for Dysport has been shown as soon as 1 day with 25% of patients and a median onset time of 2 or 3 days compared to Botox, which showed a 68% response rate in patients at day 7. Diffusion Characteristics There has been much discussion about diffusion with Dysport. While when comparing the package inserts for these products, there seems to be slightly more diffusion from this product than from Botox, there doesn’t seem to be any increased incidence of ptosis or ocular-related events in the trials when compared to Botox. The concept of improved coverage due to diffusion is one that this author looks forward to testing in practice. Where there are challenges on upper foreheads with Botox at times, Dysport may provide an advantage due to its diffusion. Additionally, a smoother appearance after Dysport use may be another advantage because of the field of spread. Botox holds the advantage in patients where there is a concern for brow ptosis, in this author’s opinion. Longevity Phase III studies have shown Botox to have a 50% survival rate in 45% of patients at 90 days at a dose of 20 units, while Dysport demonstrated statistically significant improvements in glabellar line severity at day 120 using a 50 units dose and at day 150 for a variable dose, according to package inserts. Side Effects The side effect profiles of both Botox and Dysport are similar, based on studies released to the public. One study in Europe showed a slightly higher incidence of hand weakness when using Dysport in doses of 4:1 (a higher dose than this author would recommend) for hyperhidrosis.2 Another study, which was done on cervical dystonia, showed that with a dose of 3:1, Dysport showed a complication rate of 58% versus 69% with Botox and similar efficacy.3 In a study by Hexsel et al using a dosing ratio of 2.5:1, there were no diffusion-related issues when treating frontalis muscles and lateral periorbital areas.4 While this dosage is not the one that this author would choose, there is the possibility of some diffusion-related differences in the 3:1 ratio. (The Hexsel study was funded by Ipsen, the maker of Dysport.) Potential Areas of Future Research for Dysport While most, if not all, of the current studies on new forms of botulinum toxin are centered on use in the glabellar area, there is no doubt that this drug is being used for other areas including hyperhidrosis, periorbital areas, frontalis muscle activity, platysma, depressor anguli oris, among many; research will hopefully report on this usage. One recent study by Hexsel serves to clarify this issue to some degree.1 Additionally, there are other considerations for topical use of peptides for novel indications that are being researched by several companies, including research on topical treatment of hyperhidrosis.5 Competition In United States: Post-Approval Pricing Issues Competition among the toxins is already fierce, with several other cosmetic products being offered by the companies that are supplying Dysport or developing other forms of this product. A vial of Dysport currently costs $50 less than a vial of Botox, which may challenge Allergen to respond with a price reduction. Time will tell, but it doesn’t seem likely that there will be significant savings due to competition. This mirrors the economic model of a duopoly in many ways. Once there are many players in this field, competition may become more heated and be reflected in price decreases, but that may also be restricted by Medicare rules that apply to products with medical as well as cosmetic indications and are paid via Medicare reimbursement. While some price savings have already been seen with the introduction of other, newer forms of fillers and Dysport in the United States, the price savings have typically gone to those individuals who purchase larger amounts or who purchase both types of fillers and neurotoxins from one company. Outside the United States There are at least three countries where Dysport has already gone head to head with Botox, including Germany, where both were launched in 1993, and Dysport reportedly is the market leader. In the UK and France, Dysport is approved only for medical indications, yet apparently is being used to some degree in the aesthetic arena. According to personal communication with Medical Affairs at Medicis, Dysport is the market leader in Russia, Ukraine and several other Eastern EU countries, Iran and possibly Brazil. Figures aren’t readily available, so reports on markets are based on market analysis by venture capital firms. Dr. Schlessinger is a board certified dermatologist and cosmetic surgeon in private practice in Omaha, NE. He is President Emeritus, American Society of Cosmetic Dermatology and Aesthetic Surgery. Disclosures: Dr. Schlessinger is currently an investigator for Medicis, Merz, Mentor and Revance. He has performed research for Allergan previously as well. _____________________ Further Reading 1. Rzany B, Ascher B, Fratila A, Monheit GD, Talarico S, Sterry W. Efficacy and safety of 3- and 5-injection patterns (30 and 50 U) of botulinum toxin A (Dysport) for the treatment of wrinkles in the glabella and the central forehead region. Arch Dermatol. 2006 Mar;142(3):320-6. 2. Rzany B et al. Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg. 2007 Jan;33(1 Spec No.):S18-25. 3. Farahvash MR, Arad S. Clostridium botulinum type A toxin for the treatment of upper face animation lines: an Iranian experience. J Cosmet Dermatol. 2007 Sep;6(3):152-8. ______________________ Save The Date Dr. Schlessinger invites you to attend his new meeting, Cosmetic Surgery Forum 2009, a multi-specialty forum to facilitate education and discourse on the most relevant issues in dermatology and cosmetic surgery. This meeting will be attended by industry experts and physicians from the fields of dermatology, cosmetic surgery, and plastic surgery. The meeting will be held December 4 to 6 at The Palazzo at the Venetian. For more information, or to register, please visit www.Cosmetic SurgeryForum.com.
A NEW FORM OF BOTULINUM TOXIN
While Botox Cosmetic was the first, there are now many toxins in various stages of development. Since FDA approval of Dysport, the big question is how this new form of botulinum toxin will stand up to the titan of toxins. Recently, a new form of botulinum toxin, Dysport, became available in the marketplace. Given the fact that 203,000 hits on Google come up when searching “Dysport” as compared to 803,000 for “botulinum toxin,” this event has clearly been of great interest to the general public and media. But while the advent of this and other new forms of botulinum toxin has been highly anticipated, the big question in the minds of many — including this investigator — is whether they will be able to live up to the hype? What’s New The main new forms of botulinum toxin in Phase III clinical trials are PurTox (Mentor Corporation) and NT201 (Merz Pharmaceuticals). Additionally, there are other forms of toxins from China, Brazil and South Korea that are being tested in countries other than the United States. As Dysport was recently approved by the FDA, this discussion will focus upon the characteristics of this Medicis product in comparison to Allergen’s Botox Cosmetic. Dysport VS. Botox Characteristics Molecule Each botulinum toxin batch contains a slightly different molecule, so it is no surprise that the Dysport molecule isn’t exactly the same as the Botox molecule. On the other hand, the similarities between them are quite striking, with both molecules being in the 900 kilodalton size range, with a 150 KD subunit, the active toxin molecule, which is surrounded by non-toxin associated proteins, resulting in the 900 KD size. There are various subunits that make this configuration possible. Composition While Botox is prepared with human albumin in the vial, the Dysport vial contains both lactose and albumin. Both vials contain toxin-associated peptides. It is unlikely that the lactose in the Dysport vial will result in any problems for those who are lactose-intolerant due to the fact that lactose intolerance is specific for gastrointestinal enzymes and isn’t an allergy, per se. Strength While there have been no firm comparison trials for Botox versus Dysport, Dysport is supplied in vials of 300 units, which will be fairly equivalent to 100 units of Botox. Studies performed in Europe and the clinical trials in the United States on Dysport have shown a conversion ratio of 2.5:1 to be a good starting point, while a conversion rate of 4:1 typically results in higher rates of adverse reactions. With the use of a 300-unit vial, it appears that the material will be reconstituted in the same manner as Botox and will treat approximately the same number of patients or slightly more than a 100 unit vial of Botox (assuming a 2.5:1 conversion ratio). Time Available for Use While many studies have shown that reconstituted Botox retains activity for longer than the 4 hours noted in the package insert, that is the time of usage for Botox as per package insert (PI). Dysport has a PI time of use of 8 hours in the EU, yet a recent study by Doris Hexsel shows activity of Dysport 15 days after reconstitution.1 Time to Onset Time to onset for Dysport has been shown as soon as 1 day with 25% of patients and a median onset time of 2 or 3 days compared to Botox, which showed a 68% response rate in patients at day 7. Diffusion Characteristics There has been much discussion about diffusion with Dysport. While when comparing the package inserts for these products, there seems to be slightly more diffusion from this product than from Botox, there doesn’t seem to be any increased incidence of ptosis or ocular-related events in the trials when compared to Botox. The concept of improved coverage due to diffusion is one that this author looks forward to testing in practice. Where there are challenges on upper foreheads with Botox at times, Dysport may provide an advantage due to its diffusion. Additionally, a smoother appearance after Dysport use may be another advantage because of the field of spread. Botox holds the advantage in patients where there is a concern for brow ptosis, in this author’s opinion. Longevity Phase III studies have shown Botox to have a 50% survival rate in 45% of patients at 90 days at a dose of 20 units, while Dysport demonstrated statistically significant improvements in glabellar line severity at day 120 using a 50 units dose and at day 150 for a variable dose, according to package inserts. Side Effects The side effect profiles of both Botox and Dysport are similar, based on studies released to the public. One study in Europe showed a slightly higher incidence of hand weakness when using Dysport in doses of 4:1 (a higher dose than this author would recommend) for hyperhidrosis.2 Another study, which was done on cervical dystonia, showed that with a dose of 3:1, Dysport showed a complication rate of 58% versus 69% with Botox and similar efficacy.3 In a study by Hexsel et al using a dosing ratio of 2.5:1, there were no diffusion-related issues when treating frontalis muscles and lateral periorbital areas.4 While this dosage is not the one that this author would choose, there is the possibility of some diffusion-related differences in the 3:1 ratio. (The Hexsel study was funded by Ipsen, the maker of Dysport.) Potential Areas of Future Research for Dysport While most, if not all, of the current studies on new forms of botulinum toxin are centered on use in the glabellar area, there is no doubt that this drug is being used for other areas including hyperhidrosis, periorbital areas, frontalis muscle activity, platysma, depressor anguli oris, among many; research will hopefully report on this usage. One recent study by Hexsel serves to clarify this issue to some degree.1 Additionally, there are other considerations for topical use of peptides for novel indications that are being researched by several companies, including research on topical treatment of hyperhidrosis.5 Competition In United States: Post-Approval Pricing Issues Competition among the toxins is already fierce, with several other cosmetic products being offered by the companies that are supplying Dysport or developing other forms of this product. A vial of Dysport currently costs $50 less than a vial of Botox, which may challenge Allergen to respond with a price reduction. Time will tell, but it doesn’t seem likely that there will be significant savings due to competition. This mirrors the economic model of a duopoly in many ways. Once there are many players in this field, competition may become more heated and be reflected in price decreases, but that may also be restricted by Medicare rules that apply to products with medical as well as cosmetic indications and are paid via Medicare reimbursement. While some price savings have already been seen with the introduction of other, newer forms of fillers and Dysport in the United States, the price savings have typically gone to those individuals who purchase larger amounts or who purchase both types of fillers and neurotoxins from one company. Outside the United States There are at least three countries where Dysport has already gone head to head with Botox, including Germany, where both were launched in 1993, and Dysport reportedly is the market leader. In the UK and France, Dysport is approved only for medical indications, yet apparently is being used to some degree in the aesthetic arena. According to personal communication with Medical Affairs at Medicis, Dysport is the market leader in Russia, Ukraine and several other Eastern EU countries, Iran and possibly Brazil. Figures aren’t readily available, so reports on markets are based on market analysis by venture capital firms. Dr. Schlessinger is a board certified dermatologist and cosmetic surgeon in private practice in Omaha, NE. He is President Emeritus, American Society of Cosmetic Dermatology and Aesthetic Surgery. Disclosures: Dr. Schlessinger is currently an investigator for Medicis, Merz, Mentor and Revance. He has performed research for Allergan previously as well. _____________________ Further Reading 1. Rzany B, Ascher B, Fratila A, Monheit GD, Talarico S, Sterry W. Efficacy and safety of 3- and 5-injection patterns (30 and 50 U) of botulinum toxin A (Dysport) for the treatment of wrinkles in the glabella and the central forehead region. Arch Dermatol. 2006 Mar;142(3):320-6. 2. Rzany B et al. Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg. 2007 Jan;33(1 Spec No.):S18-25. 3. Farahvash MR, Arad S. Clostridium botulinum type A toxin for the treatment of upper face animation lines: an Iranian experience. J Cosmet Dermatol. 2007 Sep;6(3):152-8. ______________________ Save The Date Dr. Schlessinger invites you to attend his new meeting, Cosmetic Surgery Forum 2009, a multi-specialty forum to facilitate education and discourse on the most relevant issues in dermatology and cosmetic surgery. This meeting will be attended by industry experts and physicians from the fields of dermatology, cosmetic surgery, and plastic surgery. The meeting will be held December 4 to 6 at The Palazzo at the Venetian. For more information, or to register, please visit www.Cosmetic SurgeryForum.com.
While Botox Cosmetic was the first, there are now many toxins in various stages of development. Since FDA approval of Dysport, the big question is how this new form of botulinum toxin will stand up to the titan of toxins. Recently, a new form of botulinum toxin, Dysport, became available in the marketplace. Given the fact that 203,000 hits on Google come up when searching “Dysport” as compared to 803,000 for “botulinum toxin,” this event has clearly been of great interest to the general public and media. But while the advent of this and other new forms of botulinum toxin has been highly anticipated, the big question in the minds of many — including this investigator — is whether they will be able to live up to the hype? What’s New The main new forms of botulinum toxin in Phase III clinical trials are PurTox (Mentor Corporation) and NT201 (Merz Pharmaceuticals). Additionally, there are other forms of toxins from China, Brazil and South Korea that are being tested in countries other than the United States. As Dysport was recently approved by the FDA, this discussion will focus upon the characteristics of this Medicis product in comparison to Allergen’s Botox Cosmetic. Dysport VS. Botox Characteristics Molecule Each botulinum toxin batch contains a slightly different molecule, so it is no surprise that the Dysport molecule isn’t exactly the same as the Botox molecule. On the other hand, the similarities between them are quite striking, with both molecules being in the 900 kilodalton size range, with a 150 KD subunit, the active toxin molecule, which is surrounded by non-toxin associated proteins, resulting in the 900 KD size. There are various subunits that make this configuration possible. Composition While Botox is prepared with human albumin in the vial, the Dysport vial contains both lactose and albumin. Both vials contain toxin-associated peptides. It is unlikely that the lactose in the Dysport vial will result in any problems for those who are lactose-intolerant due to the fact that lactose intolerance is specific for gastrointestinal enzymes and isn’t an allergy, per se. Strength While there have been no firm comparison trials for Botox versus Dysport, Dysport is supplied in vials of 300 units, which will be fairly equivalent to 100 units of Botox. Studies performed in Europe and the clinical trials in the United States on Dysport have shown a conversion ratio of 2.5:1 to be a good starting point, while a conversion rate of 4:1 typically results in higher rates of adverse reactions. With the use of a 300-unit vial, it appears that the material will be reconstituted in the same manner as Botox and will treat approximately the same number of patients or slightly more than a 100 unit vial of Botox (assuming a 2.5:1 conversion ratio). Time Available for Use While many studies have shown that reconstituted Botox retains activity for longer than the 4 hours noted in the package insert, that is the time of usage for Botox as per package insert (PI). Dysport has a PI time of use of 8 hours in the EU, yet a recent study by Doris Hexsel shows activity of Dysport 15 days after reconstitution.1 Time to Onset Time to onset for Dysport has been shown as soon as 1 day with 25% of patients and a median onset time of 2 or 3 days compared to Botox, which showed a 68% response rate in patients at day 7. Diffusion Characteristics There has been much discussion about diffusion with Dysport. While when comparing the package inserts for these products, there seems to be slightly more diffusion from this product than from Botox, there doesn’t seem to be any increased incidence of ptosis or ocular-related events in the trials when compared to Botox. The concept of improved coverage due to diffusion is one that this author looks forward to testing in practice. Where there are challenges on upper foreheads with Botox at times, Dysport may provide an advantage due to its diffusion. Additionally, a smoother appearance after Dysport use may be another advantage because of the field of spread. Botox holds the advantage in patients where there is a concern for brow ptosis, in this author’s opinion. Longevity Phase III studies have shown Botox to have a 50% survival rate in 45% of patients at 90 days at a dose of 20 units, while Dysport demonstrated statistically significant improvements in glabellar line severity at day 120 using a 50 units dose and at day 150 for a variable dose, according to package inserts. Side Effects The side effect profiles of both Botox and Dysport are similar, based on studies released to the public. One study in Europe showed a slightly higher incidence of hand weakness when using Dysport in doses of 4:1 (a higher dose than this author would recommend) for hyperhidrosis.2 Another study, which was done on cervical dystonia, showed that with a dose of 3:1, Dysport showed a complication rate of 58% versus 69% with Botox and similar efficacy.3 In a study by Hexsel et al using a dosing ratio of 2.5:1, there were no diffusion-related issues when treating frontalis muscles and lateral periorbital areas.4 While this dosage is not the one that this author would choose, there is the possibility of some diffusion-related differences in the 3:1 ratio. (The Hexsel study was funded by Ipsen, the maker of Dysport.) Potential Areas of Future Research for Dysport While most, if not all, of the current studies on new forms of botulinum toxin are centered on use in the glabellar area, there is no doubt that this drug is being used for other areas including hyperhidrosis, periorbital areas, frontalis muscle activity, platysma, depressor anguli oris, among many; research will hopefully report on this usage. One recent study by Hexsel serves to clarify this issue to some degree.1 Additionally, there are other considerations for topical use of peptides for novel indications that are being researched by several companies, including research on topical treatment of hyperhidrosis.5 Competition In United States: Post-Approval Pricing Issues Competition among the toxins is already fierce, with several other cosmetic products being offered by the companies that are supplying Dysport or developing other forms of this product. A vial of Dysport currently costs $50 less than a vial of Botox, which may challenge Allergen to respond with a price reduction. Time will tell, but it doesn’t seem likely that there will be significant savings due to competition. This mirrors the economic model of a duopoly in many ways. Once there are many players in this field, competition may become more heated and be reflected in price decreases, but that may also be restricted by Medicare rules that apply to products with medical as well as cosmetic indications and are paid via Medicare reimbursement. While some price savings have already been seen with the introduction of other, newer forms of fillers and Dysport in the United States, the price savings have typically gone to those individuals who purchase larger amounts or who purchase both types of fillers and neurotoxins from one company. Outside the United States There are at least three countries where Dysport has already gone head to head with Botox, including Germany, where both were launched in 1993, and Dysport reportedly is the market leader. In the UK and France, Dysport is approved only for medical indications, yet apparently is being used to some degree in the aesthetic arena. According to personal communication with Medical Affairs at Medicis, Dysport is the market leader in Russia, Ukraine and several other Eastern EU countries, Iran and possibly Brazil. Figures aren’t readily available, so reports on markets are based on market analysis by venture capital firms. Dr. Schlessinger is a board certified dermatologist and cosmetic surgeon in private practice in Omaha, NE. He is President Emeritus, American Society of Cosmetic Dermatology and Aesthetic Surgery. Disclosures: Dr. Schlessinger is currently an investigator for Medicis, Merz, Mentor and Revance. He has performed research for Allergan previously as well. _____________________ Further Reading 1. Rzany B, Ascher B, Fratila A, Monheit GD, Talarico S, Sterry W. Efficacy and safety of 3- and 5-injection patterns (30 and 50 U) of botulinum toxin A (Dysport) for the treatment of wrinkles in the glabella and the central forehead region. Arch Dermatol. 2006 Mar;142(3):320-6. 2. Rzany B et al. Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients. Dermatol Surg. 2007 Jan;33(1 Spec No.):S18-25. 3. Farahvash MR, Arad S. Clostridium botulinum type A toxin for the treatment of upper face animation lines: an Iranian experience. J Cosmet Dermatol. 2007 Sep;6(3):152-8. ______________________ Save The Date Dr. Schlessinger invites you to attend his new meeting, Cosmetic Surgery Forum 2009, a multi-specialty forum to facilitate education and discourse on the most relevant issues in dermatology and cosmetic surgery. This meeting will be attended by industry experts and physicians from the fields of dermatology, cosmetic surgery, and plastic surgery. The meeting will be held December 4 to 6 at The Palazzo at the Venetian. For more information, or to register, please visit www.Cosmetic SurgeryForum.com.
