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Serono: innovative research in reproductive health and infertility
INDUSTRY UPDATE
Serono: Innovative Research in Reproductive Health and Infertility Paul Lammers, M.D. Chief Medical Officer, Serono, Inc.
The number of couples delaying childbirth is increasing and one out of five American women is having a first child after the age of 35. As a consequence, infertility is becoming more commonplace and the challenges in reproductive health and infertility are growing. The need for innovative research is as compelling as ever. The keys to research in the field over the next several years are furthering our understanding of the biology of reproduction and targeting unmet medical needs. erono’s current pipeline in reproductive health and infertility is a prime example of this focus. As a pioneer and innovator in the field for more than 70 years, Serono offers the first and only fully recombinant portfolio of gonadotropins for the most important stages of the infertility treatment cycle and is committed to the research and development of advances that improve upon existing treatments, are patient friendly and address areas still without adequate therapies.
S
Understanding Biology to Target Unmet Medical Needs An understanding of biology is helping researchers address unmet medical needs in two areas - embryo implantation failure and premature labor. Embryo implantation failure is a major cause of infertility and is responsible for more than 50% of IVF failures. We know that leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is present in the endometrium and a mediator involved in processes associated with implantation and in early embryonic development. Recombinant emfilermin (r-LIF), licensed from AMRAD, Australia, may have a therapeutic role in overcoming embryo implantation failure following IVF. The product is currently undergoing a proof of concept study.
Sexuality, Reproduction & Menopause, Vol. 2, No. 1, March 2004 © 2004 American Society for Reproductive Medicine Published by Elsevier Inc.
53
With biology as the foundation, Serono is also investigating two approaches to the problem of premature labor. Oxytocin and prostaglandin F2a have been linked with uterine contractility, and receptors for both are up regulated in myometrial tissue during labor. In animal models, oxytocin and prostaglandin antagonists have been shown to be effective in switching off uterine contractility, which results in pregnancies being carried to full term. A Phase 1 trial for an oxytocin antagonist is underway, and a prostanoid F2-alpha Prostaglandin (FP) receptor antagonist is ready for preclinical evaluation. The unmet medical needs of rare patient populations are also being addressed by current research at Serono. One such patient group is infertile hypogonadotropic hypogonadal (HH) women with profound luteinizing hormone deficiency (LH ⬍ 1.2 IU/L). HH is a rare endocrine deficiency affecting between 2,800 and 5,600 women in the US and can range from mild to severe. Luveris® (lutropin alfa for injection) administered with follitropin alfa for injection, is under consideration by the FDA and is proposed for the indication of stimulation of follicular development in profoundly deficient HH women. Luveris® is currently approved in more than 40 countries worldwide.
Patient Friendly A key for many patients undergoing infertility treatment is reducing the need for daily injections. With Alkermes, Inc., Serono is working on a sustained release formulation of recombinant FSH. The aim is to deliver sufficient r-hFSH in a single injection for the first 5–10 days of an infertility treatment cycle. The project combines Serono’s recombinant FSH and Alkermes’ patented technology for sustained release drug formulation development. Phase 1 studies demonstrated clear evidence of dose dependent response in the important indices of follicular growth and estradiol production. The project is now progressing to Phase 2. Serono is also conducting a Phase 2 clinical trial in the U.S. with anastrozole, which could be a single dose, oral treatment for ovulation induction and follicular development. The primary endpoint of the trial is the ovulation rate in the anastrozole arms as compared with the clomiphene citrate control group. As an aromatase inhibitor, anastrozole is expected to have a lesser anti-estrogenic effect than clomiphene citrate. Results from the study are expected sometime in the second half of 2004.
Research Strategy Serono continues its strong focus on drug discovery programs for reproductive health and infertility. Serono is looking at ways to develop new and better drugs, both small molecules and protein therapeutics, to optimize success in assisted reproductive technology and target unmet medical needs. As a world leader in biotechnology, Serono also has strong positions in neurology, and growth and metabolism. The company has more than 30 projects in development, which are focused on growing its existing businesses and establishing new therapeutic areas.
Paul Lammers Chief Medical Officer Serono, Inc. One Technology Place Rockland, MA 02370 [email protected]
54
Sexuality, Reproduction & Menopause, Vol. 2, No. 1, March 2004
Serono: Innovative Research in Reproductive Health and Infertility Paul Lammers, M.D. Chief Medical Officer, Serono, Inc.
The number of couples delaying childbirth is increasing and one out of five American women is having a first child after the age of 35. As a consequence, infertility is becoming more commonplace and the challenges in reproductive health and infertility are growing. The need for innovative research is as compelling as ever. The keys to research in the field over the next several years are furthering our understanding of the biology of reproduction and targeting unmet medical needs. erono’s current pipeline in reproductive health and infertility is a prime example of this focus. As a pioneer and innovator in the field for more than 70 years, Serono offers the first and only fully recombinant portfolio of gonadotropins for the most important stages of the infertility treatment cycle and is committed to the research and development of advances that improve upon existing treatments, are patient friendly and address areas still without adequate therapies.
S
Understanding Biology to Target Unmet Medical Needs An understanding of biology is helping researchers address unmet medical needs in two areas - embryo implantation failure and premature labor. Embryo implantation failure is a major cause of infertility and is responsible for more than 50% of IVF failures. We know that leukemia inhibitory factor (LIF), a member of the IL-6 cytokine family, is present in the endometrium and a mediator involved in processes associated with implantation and in early embryonic development. Recombinant emfilermin (r-LIF), licensed from AMRAD, Australia, may have a therapeutic role in overcoming embryo implantation failure following IVF. The product is currently undergoing a proof of concept study.
Sexuality, Reproduction & Menopause, Vol. 2, No. 1, March 2004 © 2004 American Society for Reproductive Medicine Published by Elsevier Inc.
53
With biology as the foundation, Serono is also investigating two approaches to the problem of premature labor. Oxytocin and prostaglandin F2a have been linked with uterine contractility, and receptors for both are up regulated in myometrial tissue during labor. In animal models, oxytocin and prostaglandin antagonists have been shown to be effective in switching off uterine contractility, which results in pregnancies being carried to full term. A Phase 1 trial for an oxytocin antagonist is underway, and a prostanoid F2-alpha Prostaglandin (FP) receptor antagonist is ready for preclinical evaluation. The unmet medical needs of rare patient populations are also being addressed by current research at Serono. One such patient group is infertile hypogonadotropic hypogonadal (HH) women with profound luteinizing hormone deficiency (LH ⬍ 1.2 IU/L). HH is a rare endocrine deficiency affecting between 2,800 and 5,600 women in the US and can range from mild to severe. Luveris® (lutropin alfa for injection) administered with follitropin alfa for injection, is under consideration by the FDA and is proposed for the indication of stimulation of follicular development in profoundly deficient HH women. Luveris® is currently approved in more than 40 countries worldwide.
Patient Friendly A key for many patients undergoing infertility treatment is reducing the need for daily injections. With Alkermes, Inc., Serono is working on a sustained release formulation of recombinant FSH. The aim is to deliver sufficient r-hFSH in a single injection for the first 5–10 days of an infertility treatment cycle. The project combines Serono’s recombinant FSH and Alkermes’ patented technology for sustained release drug formulation development. Phase 1 studies demonstrated clear evidence of dose dependent response in the important indices of follicular growth and estradiol production. The project is now progressing to Phase 2. Serono is also conducting a Phase 2 clinical trial in the U.S. with anastrozole, which could be a single dose, oral treatment for ovulation induction and follicular development. The primary endpoint of the trial is the ovulation rate in the anastrozole arms as compared with the clomiphene citrate control group. As an aromatase inhibitor, anastrozole is expected to have a lesser anti-estrogenic effect than clomiphene citrate. Results from the study are expected sometime in the second half of 2004.
Research Strategy Serono continues its strong focus on drug discovery programs for reproductive health and infertility. Serono is looking at ways to develop new and better drugs, both small molecules and protein therapeutics, to optimize success in assisted reproductive technology and target unmet medical needs. As a world leader in biotechnology, Serono also has strong positions in neurology, and growth and metabolism. The company has more than 30 projects in development, which are focused on growing its existing businesses and establishing new therapeutic areas.
Paul Lammers Chief Medical Officer Serono, Inc. One Technology Place Rockland, MA 02370 [email protected]
54
Sexuality, Reproduction & Menopause, Vol. 2, No. 1, March 2004