Shire Pharmaceuticals has submitted their latest product, Lifitegrast, to the U.S. Food and Drug Administration (FDA). However, the FDA has declined registration. The product is designed to treat the symptoms of Dry Eye Syndrome (DES) in adult populations. The FDA sent Shire Pharmaceuticals a letter requesting more information on October 16, 2015. Specifically, they requested further studies to be included. Shire has now resubmitted their new drug application (NDA), including an OPUS-3, which is a phase 3 safety and efficacy trial. This trial reports symptom improvement as experienced by patients. Furthermore, Shire added information regarding the quality of the product, as per the FDAs request.
A Timeline of Lifitegrast
The table below highlights the various stages that Lifitegrast has gone through.
| Date | Action |
| May 16, 2014 | Shire intends to submit their first NDA for their Lifitegrast product, developed for the treatment of adult DES. |
| March 2, 2015 | The first NDA is submitted to the FDA for approval. |
| April 9, 2015 | The FDA grants a priority review for the Lifitegrast NDA. |
| October 16, 2015 | FDA sends complete response letter to Shire, prompting Shire to start an OPUS-3 trial. |
| January 25, 2016 | Shire resubmits NDA to FDA for Lifitegrast. |
| February 4, 1016 | FDA acknowledges resubmission of Lifitegrast NDA |
The New Drug Application
In the latest new drug application, Shire has included data from five different controlled and randomized clinical trials. Over 2,500 patients have taken part in these trials, which means it is the largest study of its kind looking specifically at dry eye syndrome. Shire believes that Lifitegrast, if it receives FDA approval, could help the millions of adults in this country who currently suffer from DES. As such, they have diligently worked to make sure the FDA’s requests were responded to as soon as possible. Shire feels that this is true testament to the fact that they are committed to creating treatment options within fields where medical need is currently unmet.
The latest NDA includes:
- One phase 2 study data set
- Three phase 3 study data sets, looking at efficacy and safety (OPUS-1, 2, and 3)
- One phase 3 SONATA study, that took one year to complete
- The FDA has six months to respond to the NDA. This means that, if approved, Lifitegrast could be available by November 2016.
What Is Lifitegrast?
Lifitegrast is a chemical compound that binds to the integrin LFA-1 (lymphocyte function-associated antigen). This is a protein found on the surface of leukocyte cells and it blocks the LFA-1’s interaction with ICAM-1 (cognate ligand intercellular adhesion module). Studies have shown that people with DES have higher build ups of ICAM-1 in their conjunctival and corneal tissues. It is believed, therefore, that the interaction between LFA-1 and ICAM-1 forces an immunological response in the body, activating T-cells, which migrate to target tissues.
A number of in vitro studies have been completed, and these have shown that Lifitegrast can stop T-cells from sticking to ICAM-1 expressing cells. Furthermore, it stops the secretion of cytokines that cause inflammation. The various cytokines that it is able to respond to are all known to be linked to DES.
What Is OPUS-3?
During the OPUS-3 trial, scientists looked at the safety and efficacy of Lifitegrast, comparing it to a placebo group and a control group. The results of the study showed that those who were given the drug reported a significant improvement in their DES symptoms. These results were noticed quite rapidly, and improved as time went on.
What Is DES?
DES is a common condition that affects the eyes. Two types of DES exist, one being insufficient tear production, and the other being a reduction in the quality of the tears. An ophthalmologist, optician, or other eye specialist is able to diagnose the condition from reported symptoms. Common symptoms include:
- Dryness of the eye
- Discomfort of the eye
- Burning and stinging
- Feelings of grittiness or having a foreign body in the eye
- Blurry vision
A number of medical tests exist to diagnose DES, including:
- Tear break up time (TBUT) tests
- Conjunctival lissamine green staining
- Corneal fluorescein staining
- Schirmer test
It is known that there are a number of risk factors that may contribute to the development of DES, including:
- Genetic factors
- Wearing contact lenses
- Prolonged use of computer and digital screens, known as Computer Vision Syndrome or CVS
- Refractive surgery
- Cataract surgery
- LASIK eye surgery
The condition is chronic and causes inflammation. This, in turn, may lead to surface damage of the eye. It is for this reason that the condition is classed as progressive. It is also one of the most common reasons people have for wanting to see an eye specialist.
Shire and Ophthalmics
Shire has made a public commitment to finding new and improved treatment methods for ophthalmological conditions, including DES. They focus on discovery, development, and delivery, specifically in diseases with an unmet medical need, and in rare diseases. The company has made a number of strategic acquisitions, as well as experiencing organic growth. They have built a solid reputation as being one of the globe’s leading biotech companies.
Currently, Shire’s ophthalmics portfolio is quite significant. It includes a number of treatment options for posterior and anterior segment eye conditions. However, the company is committed to further expanding their portfolio. This is why they have made a number of significant acquisitions as of late, in order to grow this element of their business. Their acquisitions include:
- BIKAM Pharmaceuticals
- Premacure AB
- SARcode Biosceince
- Foresight Biotherapeutics
Currently, they focus on a number of specific eye conditions:
- Glaucoma
- Autosomal dominant retinitis pigmentosa
- Retinopathy of prematurity
- Infectious conjunctivitis
- Dry eye disease
To date, people who suffer from DES only have Restasis, a blockbuster drug created by Allergan, to cope with their symptoms. It is the only drug that currently has FDA approval for the treatment of DES. Restasis is a therapeutic based on cyclosporine, providing patients with clinical benefits by reducing their ocular inflammation. The fact that Shire is offering competition through its Lifitegrast product has filled the market with confidence.
An added benefit is that patients are often not happy with Restasis. This is because the drug takes quite a long time before it becomes effective, and some people find their symptoms actually get worse before they get better. This has prompted a lot of patients to stop using the product before they are able to experience any real benefits.
Shire is hopeful that Lifitegrast will be available on the market this year. The FDA has a period of six months after acknowledgement of receipt to make a decision due to the fact that the drug has been granted priority status. As such, the product could potentially hit the shelves before the end of the year.
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