Biotech Strategy Blog

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

Posts tagged ‘teriparatide’

Contrary to popular opinion, innovation is not dead in the biomedical industry, as evidenced by news of a novel drug-delivery system published as a Rapid Publication in Science Translational Medicine (STM) on February 16, 2012.

The paper from Robert Farra of MicroCHIPS, Inc. and research collaborators, describes a first-in-human testing of a wirelessly controlled drug delivery microchip.

Farra et al., report the results of a clinical trial with 8 women in whom microchips were implanted for 103 days. The data showed that the pharmacokinetic profile of microgram-quantities of the anti-osteoporosis drug, teriparatide (FORSTEO), delivered by the microchip was similar to subcutaneous injections.  However, the device did fail in one of the 8 women, so data is only reported for 7 patients, a very small patient sample.

Picture Credit: MicroCHIPS, Inc.

The drug delivery device is an array of 600-nL micro reservoirs in which the drug is stored, that is associated with a 13.0 mm x 5.4mm x 0.5mm silicon chip.

The microchip was implanted beneath the skin (subcutaneously) in the abdomen by creating a 2.5cm incision, performed during an outpatient visit.

This paper is also interesting for its use of telemedicine. A remote operator was able to establish a wireless link and send instructions directly to the implant on dosing schedule as well as receive information back on operation of the chip.

John T. Watson, Professor of Bioengineering at the University of California San Diego  commented in the accompanying editorial that:

“The microchip represents more than 10 years of engineering design and development efforts to arrive at a programmable, implantable device for subcutaneous release of a therapeutic agent in discrete doses.”

Multiple engineering design advances were made along the way.

He also noted the results from the quality-of-life surveys administered during the trial; the majority of women stating they often forgot they had the device implanted and would readily consent to a fresh implant if needed.

Innovations in drug delivery offer hope of an improved quality of life to patients with chronic disease who require daily injections.  In 2010, there were approximately 50,000 teriparatide users, not an insignificant market opportunity.  People with diabetes who require daily injection of insulin is another potential market that springs to mind.

The first-in-human results reported in Science Translational Medicine show promise and the potential of a novel implanted wireless drug delivery system.

However, many questions remain unanswered by this research including the reliability & durability of the microchip device, given that it failed in 1 out of 8 women implanted.

Further work on validating the technology, and confirming its safety, reliability and efficacy in a larger sample size will be needed before it can obtain regulatory approval.

References

ResearchBlogging.orgFarra, R., Sheppard, N., McCabe, L., Neer, R., Anderson, J., Santini, J., Cima, M., & Langer, R. (2012). First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip Science Translational Medicine DOI: 10.1126/scitranslmed.3003276

Watson, J. (2012). Re-Engineering Device Translation Timelines Science Translational Medicine DOI: 10.1126/scitranslmed.3003687

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 breastcancer.org 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.

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