“With BA058-TD, the transdermal patch, we expect the current 6-month trial to show that it is as effective as the subcutaneous delivery method. There is reason to believe it may even be more effective when delivered transdermally in highly vascularized skin, because doing so allows the administered drug to absorb into the system at a faster rate. If the transdermal works as well as the subcutaneous, we will have not only the best-in-breed anabolic drug, but also a convenient, patientpreferred delivery method we believe will improve compliance.”
Radius Health, Inc. is a biopharmaceutical company focused on developing advanced therapeutics for healthy aging. The company’s mission is to improve the quality of life in older adults by treating age-related conditions with new solutions that target osteoporosis and other women’s health conditions. Michael S. Wyzga, President and Chief Executive Officer of Radius Health, Inc., formerly served as Executive Vice President, Finance and Chief Financial Officer of Genzyme, where he held primary responsibility for the firm's financial management worldwide and provided leadership in the successful $20.1 billion sale of Genzyme to Sanofi - the second-largest acquisition in biotechnology history. Drug Development & Delivery recently interviewed Mr. Wyzga to discuss what Radius is bringing to the underserved market for women’s healthy aging solutions.
Q: According to the National Osteoporosis Foundation, the prevalence of osteoporosis is continuing to grow, yet the disease is still significantly under-recognized and under-treated. Do you see this changing in the future?
A: I believe there are three trends that will drive changes in this market. To start, we are seeing osteoporosis treatments that build and repair bone for the first time as opposed to only slowing the resorption process. Previously, there was little that could be done to rebuild the lost bone mass for patients with osteoporosis, but new therapeutics have the potential to move patients out of the fracture zone and keep them out with a “build and hold” strategy.
Second, big pharmaceutical companies like Amgen, Merck, and Eli Lilly are working on their own treatment systems to target osteoporosis. The fact that these major players in the industry are taking action underscores the unmet need of this large and growing market.
Finally, the population is aging and maintaining an increasingly mobile lifestyle. People in their 60s and 70s are remaining very active, and they are demanding better osteoporosis treatment options. We should not accept the treatment limitations of the past.
Q: The range of treatment and prevention options for osteoporosis has expanded in recent years. Can you elaborate on the new types of treatments and explain what Radius Health, Inc. is currently doing to develop new therapeutics in this area?
A: As we know, bones are constantly forming and resorbing, and this balanced process keeps bones from becoming brittle. In an osteoporosis patient, particularly postmenopausal woman, the resorption process continues, but the formation mechanism becomes weaker. Bones become brittle and more prone to breaking. The process typically begins in thinner bones like the vertebrae, where it may manifest in backaches, then moves to more dense bones, like the hip. The majority of osteoporosis treatments currently on the market are antiresorptive, which means they slow down the resorption process. However, anabolic agents assist in the building of bone and offer a solution beyond slowing resorption.
Our treatment, BA058, is a novel, synthetic proprietary peptide analog of human parathyroid hormone related protein or PTHrP, a bone-building anabolic compound. This treatment is currently in a Phase III clinical trial for a version delivered via subcutaneous injection, as well as a Phase II trial for a transdermal delivery method.
Q: In 2011, Osteoporosis International published results of a study indicating that patients' preferences for osteoporosis medications are strongly influenced by the mode of administration. What are pharmaceutical companies doing to move toward patientpreferred solutions?
A: There’s an old saying in biotech: “It’s a fascinating drug, but only if somebody uses it.” We know that a drug’s mode of administration is key, and a drug is only effective if it is used for an appropriate time period. If the treatment mechanism is cumbersome or painful, patients won’t use the drug. For example, the only available anabolic for the treatment of osteoporosis is delivered by daily subcutaneous injection and must be refrigerated. Our data suggests that the inconvenience of daily injection and the need for refrigeration significantly affects compliance rates. Between the hassle of refrigeration and the unpleasant self-injection delivery, many just give up.
Amgen has a treatment that must be administered monthly in the doctor’s office, in a series of two to three separate 1-mL injections. These injections are administered with significantly larger needles, and the patient has the added inconvenience of having to travel to the doctor’s office.
Our treatment, BA058-SC, currently in Phase III testing, is delivered via athome subcutaneous injection as well, but one key difference is it does not have to be refrigerated, which offers the potential to keep patients using it for a longer period of time. The real game changer is BA058-TD, the transdermal delivery option currently in Phase II testing. We have an exclusive agreement with 3M Drug Delivery Systems to develop and commercialize this convenient, short wear time patch that uses a Microstructured Transdermal System (MTS) from 3M Drug Delivery Systems. Studies with the BA058-TD have shown that a 5-minute wear time of the patch delivers peak drug levels consistent with subcutaneous injection. Patients can apply the patch in the morning as they are getting ready for their day and leave it on for about 5 minutes without having to deal with large needles, refrigeration, or scheduling monthly doctor visits. We believe by utilizing 3M’s innovative technology, BA058-TD has the potential to improve patient compliance significantly.
Q: What results have you received so far in the testing for BA058, and what are your expectations for the new product once it is commercialized?
A: One major difference we’ve seen compared to the currently available anabolic is that BA058 works faster. Results have shown that bone mineral density (BMD) levels increase significantly in both vertebral and non-vertebral areas. We are studying this further in the Phase III testing.
With BA058-TD, the transdermal patch, we expect the current 6-month trial to show that it is as effective as the subcutaneous delivery method. There is reason to believe it may even be more effective when delivered transdermally in highly vascularized skin, because doing so allows the administered drug to absorb into the system at a faster rate.
If the transdermal works as well as the subcutaneous, we will have not only the “best-in-breed” anabolic drug, but also a convenient, patient-preferred delivery method we believe will improve compliance.
Q: An estimated 2 million women undergo menopause every year in the US, totaling around 50 million postmenopausal women. What is currently being done in the pharmaceutical industry to address the needs of this demographic?
A: Radius has two potential products focused on helping these patients. In addition to the osteoporosis treatment, we have a product currently in Phase II testing for the treatment of “hot flashes” called 1901. While the statistics of osteoporosis are very sobering, many women seem to be equally or even more concerned with hot flashes. It’s a quality of life issue.
Hot flashes often last 4 to 5 years, and in about 20% of women, hot flashes may never go away. The night sweats and daily discomfort can be quite significant, and the currently available hormone replacement therapies with estrogen and/or progesterone have been associated with increased risks for malignancy and cardiovascular disease. We saw the need for better options, and we are developing RAD1901, a selective estrogen receptor modulator. We’ve completed a 4-week, Phase IIa study that established clinical proof of concept, and achieved a statistically significant reduction in frequency of moderate and severe hot flashes. As an alternative to conventional estrogen therapy, this treatment is very promising. It functions as an estrogen agonist in the body, promoting normal estrogen, except for in the uterus and the breast where it actually functions as an antagonist, which is what you want in order to avoid the problems associated with other therapies. This treatment will soon go into Phase IIb, another 90-day efficacy and safety study, focused on the frequency and severity of hot flashes in postmenopausal women.
Q: With several programs currently in the pipeline focused on treating osteoporosis and menopause, what can we expect to see from Radius Health, Inc. in the future?
A: We are projecting approval for BA058- SC, the subcutaneous anabolic bone builder, in 2016. The BA058-TD patch should have approval about a year later. As resources permit, we will focus on RAD1901.
We also have a drug in the preclinical phase, a selective androgen receptor modular SARM, which is a potential treatment for age-related muscle loss, frailty, and wastingtype disorders. Very often in patients with cancer or HIV, we see issues that have less to do with the primary disease than with the associated weight loss and frailty, which makes the patient susceptible to many more problems. This fits well within our focus area of healthy aging, and we look forward to making progress with this treatment.