FDA authorizes Sylentis (PharmaMar Group) to initiate Phase III trial with tivanisiran for the treatment of dry eye disease

  • This Phase III study, called SYL1001_V, will involve more than 30 hospitals in the United States.
  • It will evaluate the efficacy and safety of tivanisiran ophthalmic solution on the signs and symptoms of patients with dry eye disease associated with Sjögren’s Syndrome.
  • The study has been approved by the FDA in 30 days and will be part of the marketing authorization application.

Madrid, March 4th, 2021. – Sylentis, a PharmaMar Group company (MSE:PHM), announced today that the US FDA (Food and Drug Administration) has authorized the initiation of the Phase III clinical trial SYL1001_V with tivanisiran ophthalmic solution (eye drops), for the treatment of dry eye disease associated with Sjögren’s Syndrome.

The study design has been approved by the FDA in 30 days and will be part of the marketing authorization application, which will include another Phase III trial. In this study more than 30 hospitals in the United States and 200 patients. It is a randomized, double-masked, placebo-controlled study, the primary and secondary endpoints are, respectively, to evaluate the efficacy (signs and symptoms) and safety of tivanisiran in patients with dry eye disease, associated with Sjögren’s Syndrome. This Phase III will not be conducted in Spain.

Tivanisiran represents a breakthrough in the development of innovative drugs in different therapeutic areas through gene silencing technology based on RNA interference (RNAi). It is a drug administered in eye drops for the control of inflammation and pain, characteristic of this pathology.

Both the design of the protocol for this trial and its authorization by the regulatory authorities are based on the scientific evidence of safety and efficacy obtained in the Phase III HELIX trial[1]. This study showed a significant improvement in signs and symptoms in the subgroup of patients with Sjögren’s syndrome, which is a more severe form of dry eye disease.

Ana Isabel Jiménez, COO and head of R&D at Sylentis, said: “The initiation of this trial in the United States represents an important step towards advancing our goal of providing innovative therapies to patients with ocular surface diseases. The FDA has been very expeditious in clearing this study, giving us the go-ahead in just 30 days since we submitted it.

Explanatory videos:

What is RNA interference? https://youtu.be/T21N_dPM0_k

Dry Eye Disease: https://youtu.be/R-h_4_Yyq2g

Legal warning

This press release does not constitute an offer to sell or the solicitation of an offer to buy securities, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction.


About PharmaMar

Headquartered in Madrid, PharmaMar is a biopharmaceutical company, focused on oncology and committed to research and development which takes its inspiration from the sea to discover molecules with antitumor activity. It is a company that seeks innovative products to provide healthcare professionals with new tools to treat cancer. Its commitment to patients and to research has made it one of the world leaders in the discovery of antitumor drugs of marine origin.

PharmaMar has a pipeline of drug candidates and a robust R&D oncology program. It develops and commercializes Yondelis® in Europe and has other clinical-stage programs under development for several types of solid cancers: Zepzelca® (lurbinectedin, PM1183), PM184 and PM14. With subsidiaries in Germany, Italy, France, Switzerland, Belgium, Austria and the United States. PharmaMar wholly owns other companies: GENOMICA, a molecular diagnostics company; Sylentis, dedicated to researching therapeutic applications of gene silencing (RNAi). To learn more about PharmaMar, please visit us at www.pharmamar.com.

About Sylentis

Sylentis is a biotechnology company fully owned that develops innovative therapies harnessing the technology of post-transcriptional gene silencing or RNA interference (RNAi). Sylentis has developed an approach to efficiently design RNAi-based therapeutics that can be used to silence numerous disease-causing genes. We currently have a robust therapeutic program in ophthalmology with two candidates under development in Phase II and III studies for glaucoma (bamosiran) and ocular pain (SYL1001), respectively. Sylentis is also developing new products for the treatment of several eye diseases such as ocular allergies and retina diseases. To know more about us, please visit us at www.sylentis.com.

About tivanisiran (SYL1001)

Tivanisiran is a drug based on RNAi that is administered as preservative-free eye drops; it selectively inhibits production of the transient receptor potential cation channel (TRPV1). These receptors are ion channels that mediate the transmission of ocular pain. Tivanisiran is a small synthetic double-stranded RNA oligonucleotide (siRNA) with a novel and highly selective mechanism of action. Non-clinical studies conducted by Sylentis with SYL1001 have demonstrated it has high ability to inhibit this specific target and block the perception of ocular pain in animals.

Tivanisiran is a product under development for the treatment of signs and symptoms related to dry eye syndrome and has the potential to be developed for other pathologies that cause ocular pain (corneal lesions, refractive surgery, etc.).

About RNA interference (RNAi)

RNA interference (RNAi) is a natural cellular process that regulates the expression of certain genes, providing a role in innate defense and development in animals and plants. This process is used to specifically silence genetic transcripts that encode protein-causing diseases. The therapeutic application of targeted siRNAs is booming given the specificity of gene silencing for a particular protein in a given tissue and the lack of side effects. This new approach to drug discovery is a promising technology that is rapidly moving in the translational research space.

About Dry Eye Disease

Dry eye disease is a pathology that affects more than 344 million people worldwide for which therapeutic options are currently very limited. This disease occurs when the eye does not produce tears properly or when tears are not consistent enough and evaporate too quickly. It especially affects people in developed countries, where factors such as pollution, air conditioning, the use of contact lenses, refractive surgery or the continuous use of computers are the main causes. The most notorious symptoms of the pathology are burning, incessant itching, eye fatigue, dryness, blurred vision, sensitivity to sunlight, foreign body sensation or pain, among others.

In our country, 1 out of every 5 visits to the ophthalmologist are motivated by this problem. In fact, more than 5 million people in Spain suffer from this condition, which represents between 10% and 20% of the population. The most common profile is women mostly over 40 years of age and elderly people.

About Sjögren’s Syndrome

Sjögren’s Syndrome (SS) is an autoimmune disease that manifests as a chronic, debilitating inflammation that is mediated by the production of autoantibodies and lymphocytic infiltration and ultimately results in the permanent destruction of the exocrine glands, causing symptoms of dryness, affecting the eyes and producing dry mouth. A significant proportion of patients (about 10%) with dry eye disease have underlying Sjögren’s syndrome. This pathology is characterized by severe signs and symptoms of dry eye disease.

The estimated worldwide prevalence of Sjögren’s syndrome is 0.1% to 0.4%. The disease mainly affects women (9:1 ratio) and the peak incidence is between 40 and 60 years of age. Among people with the disorder, approximately 96% have dry eyes (93% to 100% depending on the study population).

Patients generally report symptoms of blurred vision, grittiness, pain, dryness and itching. As a result, there is a feeling of tiredness in the eyes, which they cannot cope with despite the use of eye drops. With regard to ocular signs, patients with Sjögren’s syndrome will often develop inflammation of the ocular surface, such as chronic conjunctivitis and corneal ulcers that do not heal and can lead to corneal perforation, uveitis, scleritis, retinal vasculitis and optic neuritis. In addition, this can lead to severe ocular manifestations such as decreased vision or even blindness.


[1] Press Release, HELIX Phase III trial results: https://www.pharmamar.com/wp-content/uploads/2019/01/PR_Results_HELIX_OK_v03.pdf

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