Can a Monoclonal Antibody Take Over Cheaper Drugs?

Amgen's (AMGN) denosumab (Xgeva/ Prolia) is a fully human monoclonal antibody that is FDA approved for the treatment of osteoporosis and prevention of skeletal-related events in patients with bone metastasis (a fancy way of saying that it helps to prevent cancer cells from spreading into bones and prevent fractures and pain caused by cancer cells).

A drug class called bisphophonates are typically used to treat these conditions. An example is Boniva, which had Sally Fields as a spokeswomen.  Compared to denosumab, these drugs are much cheaper , but have some serious adverse effects such as degradation of the jaw bone (osteonecrosis of the jaw).

Denosumab (Prolia) for Treatment of Osteoporosis
Cummings SR, Martin JS, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361:756-65.

• Compared to placebo, denosumab reduced the risk of vertebral fracture (2.3% denosumab, 7.2% placebo)
• Denosumab reduced the risk of hip fracture (0.7% denosumab, 1.2% placebo)
• Reduced non-vertebral fracture in denosumab group (6.5% denosumab, 8.0% placebo)
• No increased risk of cancer, infection, heart disease, slow fracture healing, injection site reactions, and no reports of osteonecrosis.
• Patients typically develop immune reactions to monoclonal antibodies (auto-antibodies) and the treatment becomes ineffective.  There have been no such reports in osteoporosis trials of denosumab, which is a good sign.
• It should be kept in mind that the trials were only a couple of years in duration and osteoporosis treatment would be lifelong.  This increases chances of immune tolerance.
• Bisphosphonates are taken usually taken weekly or monthly (Reclast is taken once a year).  the side effects are intolerable and the patient has to stand or sit up for 30-60 min after taking the dose.  Denosumab is taken twice a year.  This is a convenience factor and patients prefer the most convenient form.
• Further studies are needed comparing denosumab to bisphosphonates.  Denosumab acts through a different mechanism to prevent bone loss and may be more effective than bisphosphonates.
• Denosumab costs around $1,650 yearly.  This price should decrease as it will continue to compete with bisphosphonates.  I believe that Reclast, the once yearly bisphosphonate cost about the same.  However, Reclast requires an infusion, given over a hour or more, and Prolia is a subcutaneous injection like an insulin injection.  The cost of treatment for Prolia end up being less than Reclast.  Compound that with ease of administration and less injection reactions, expect Prolia to become the favorites  among physicians and patients.

Denosumab (XGEVA) for Treatment and Prevention of Bone Metastasis  

• Denosumab and Zometa were studied in castrate-refractory prostate cancer.
• Bone metastases occur in 1.5 million patients with cancer worldwide.  Most of these patients are debilitated by skeletal issues such as fractures and pain.
• Patients with bone metastases have higher medical costs.  Treating these skeletal issues can significantly reduce costs.
• The most common cancers associated with bone metastases  are those of the prostate, lung, and breast.
• Patients receiving XGEVA developed bone metastases about 8 months later than those taking Zometa
• Adverse effects, jaw bone degradation (osteonecrosis), overall survival, and cancer progression were similar in both groups.
• The fact that treating skeletal issues drastically reduces costs means that hospitals are acively seeking ways to treat the issue and lower their costs.
• To compete with Zometa cost wise, Amgen has begun the XGEVA FIRST STEP Coupon Program, the 1st of its kind for onocology commercial co-pay program and it does not have any income eligibility requirement.
• Patients will not have to pay out of pocket for the initial injection and only $25 for subsequent injections.
• XGEVA may become the preferred treatment for prevention of bone metastasis for similar reasons as those for osteoporosis.

Is Denosumab a Game Changer

• Denosumab is a novel way to treat osteoporosis and prevent bone metastases
• The costs are competitive vs. bisphosphonates
• Denosumab has a slightly better adverse effect profile and may be preferred by patients and physicians
• Denosumab has a high probability of being a game changer and becoming the standard of care for the approved conditions
• Further studies will need to examine adverse effects and immune tolerance
• Amgen has been trading in the $52-58 range over the past 6 months.  This can really give a boost to the stagnant stock price.