Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Prolia’

This week’s New England Journal of Medicine (NEJM) has an interesting paper (Teriparatide and Osseous Regeneration in the Oral Cavity) that caught my attention on the use of teriparatide (Eli Lilly, Forteo®) in patients with chronic peridontitis, a disease that affects one in five American adults.  The total market for periodontitis services and products is estimated to grow at 6.4% to 2016, when it will be worth $1,937 m.

Teriparatide is a recombinant form of parathyroid hormone (PTH) consisting of amino acids 1-34, and is used for the treatment of osteoporosis.  In the body, PTH is the hormone that regulates the level of calcium in the blood.  Low blood calcium causes increased PTH release. The use of teriparatide has been limited by the FDA due to the risk of osteosarcoma from long-term exposure.  However, what makes it an interesting compound is its ability to stimulate osteoblasts to build bone, which is why the results from the NEJM on peridontitis are perhaps not that surprising.

As Andrew Gray in his NEJM editorial comments, because teriparatide activates bone remodelling it may have a role to play in the management of osteonecrosis of the jaw (ONJ). ONJ is a particularly nasty side effect that many breast, multiple myeloma and prostate cancer patients experience following any dental work.

Badros et al, point out in their Journal of Clinical Oncology (JCO) paper, that bone disease effects 70% of multiple myeloma patients, many of whom take a bisphosphonate such as zoledronic acid (Novartis, Zometa®) to reduce the risk of skeletal related events (SRE). Unfortunately, a few patients subsequently end up with ONJ as a serious side effect! Clinical trial results showed that ONJ occurred with a similar frequency in breast cancer patients taking denosumab (Amgen, Prolia®) as compared to zoledronic acid.

One only has to read the patient commentary available on online forums such as to realize the debilitating effect that ONJ has, not to mention the severe morbidity because of lack of delayed diagnosis and lack of effective treatments.

It is unclear whether the positive results from the NEJM in peridontitis will lead to clinical trials for the treatment of ONJ in cancer patients.  Although there is an unmet need, the market is small. In the meantime, I expect that doctors will be using teriparatide off-label to treat severe ONJ, which is less than ideal.

One biotech company banking on continued interest in Forteo® is Zelos Therapeutics, whose CEO, Dr Brian MacDonald is a fellow alumni of the University of Sheffield.  Zelos have a nasal spray formulation of teriparatide (ZT-034), which they hope will be equivalent to Ely Lilly’s product (that requires a daily injection).

Source: Zelos Therapeutics. In a press release earlier this year, Dr MacDonald commented:

“We believe that formulation of teriparatide as a nasal spray with comparable efficacy and safety to Forteo represents a simple, convenient approach to dosing that will make PTH therapy a better option for many more patients.”

Zelos’ product is currently in early stage clinical trials, so it will be interesting to see how this develops. The NDA is planned for 2012.  It is certainly a valid strategy for emerging biotechnology companies to take an existing marketed product and use a new drug delivery mechanism such as Aegis Therapeutics’ Intravail® drug delivery technology to expand the market.

I saw the following press release from Amgen on friday evening:

Amgen Inc. (Nasdaq: AMGN) today announced that the U.S. Food and Drug Administration (FDA) has evaluated the content of the Company's Complete Response submission for Prolia(TM) (denosumab) in the treatment of postmenopausal osteoporosis and classified it as a Class 2 resubmission. With the Class 2 designation, the FDA set a corresponding Prescription Drug User Fee Act (PDUFA) action date of July 25, 2010.

The above paragraph wins a prize for one of the most unintelligible pieces of PR marketing communications I have read this year, since at first glance I was not sure what the message was i.e. whether this was good news, bad news or a piece of information that the company wanted to bury by intentionally distributing it late on a friday after the markets had shut.  So what does the above paragraph mean ?

Last October, the FDA responded to Amgen's BLA submission and in a complete response letter requested additional safety data and further information on the design of the post-marketing surveillance program.  Amgen responded to this in January this year.

Under the Prescription Drug User Fee Act (PDUFA) a submission of further information that addresses deficiencies in a BLA or NDA are classified into class 1 or class 2 resubmissions.  According to the FDA, Class 1 are minor such as final printed labeling, safety updates, stability updates and other minor clarifying information.  A Class 2 resubmission includes anything not in class 1 and any item that would require a presentation to an advisory committee. 

The PDUFA requires the FDA to review and act on 90% of class 1 resubmitted applications within 2 months of receipt, and 90 months of Class 2 resubmitted applications within 6 months of receipt. Source: FDA

In the case of denosumab, the FDA action date of July 25, 2010 is simply 6 months from when the additional information was submitted, and is the date by which the FDA must make a decision in order to hit its performance target under PDUFA.

It remains to be seen what the FDA thinks about the safety data submitted.  Denosumab is a key drug for Amgen, and any further delay in approval is likely to be taken negatively by investors given that every day of lost sales in a competitive osteoporosis market can be quantified as lost revenue.

So, the commercial significance of last friday's press release is that no approval is likely until the second half of 2010, an extended delay in the commercialization of Prolia, which is not good news for Amgen.

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