Ophthalmology

Our selected references in ophthalmology are provided below. In addition, we have gained some special expertise:

  • through our contribution to regulatory and HTA submissions we are familiar with systematic overviews of the clinical data and conducting traditional and network based meta-analyses
  • together with our partner Dokumeds we are specialized in conducting ophthalmological clinical trials – also in Eastern Europe and Russia.


Preventing Blindness - Glaucoma


Customer: Global pharmaceutical company paving its way to the global glaucoma markets with a novel prostaglandin analogue (PGA) used topically as eye drops in the management of ocular hypertension and to control the progression of glaucoma.

4Pharma’s role:
  • statistical contribution to regulatory meetings with several European authorities/EMA
  • joint development of protocols for two phase I studies, one phase II study and six phase III studies
  • data management of the studies in collaboration with the customer and several participating CROs
  • state-of-art statistical plans, analysis datasets and statistical analyses of the studies
  • medical writing of the ICH compliant clinical study reports
  • statistical contribution and joint writing of the clinical overview and summary for the dossier
  • answering regulatory authorities’ questions
  • full support to regulatory process in the U.S. (managed by a U.S. partner of the pharma company)
  • contribution to HTA negotiations and marketing material


Status: Major regulatory approvals (including EU, Japan and the US) were issued during 2008-12. In the sequel, the first entirely preservative-free (PF) PGA solution and a fixed dose combination of the PF PGA and PF beta-blocker timolol have been developed and commercialized.

Market: The value of the global market for glaucoma treatments is predicted to increase to $3.0 (€2.7) billion by 2023, according to a new report from consulting firm GlobalData. The report, which covers seven major markets for glaucoma therapeutics – the UK, France, Germany, Italy, Spain, the US and Japan – predicts that the increase will be driven by the release of a number of new drugs and fixed-dose combinations (FDCs). New drugs set to be released over the forecast period include Aerie pharmaceuticals’ Rhopressa and Roclatan, Bausch & Lomb and Nicox’s candidate drug, Vesneo, and Inotek pharma’s trabodenoson; while FDCs to emerge will include Santen’s Taptiqom and Alcon’s Simbrinza. The six products anticipated to enter the market during the forecast period will collectively generate sales of $672 (€604) million by 2023, constituting a 22.2% share of the global market.

Publications:
  • Holló G, Vuorinen J, Tuominen J, Huttunen T, Ropo A and Pfeiffer N: Fixed-dose combination of tafluprost and timolol in the treatment of open-angle glaucoma and ocular hypertension: comparison with other fixed-combination products. Adv Ther. 2014; 31(9): 932-944.


Preventing Blindness - Leber's hereditary optic neuropathy


Customer: Swiss Biotech Company specialised in orphan drugs and aiming at global markets with a novel small molecule compound for patients suffering from Leber’s hereditary optic neuropathy (LHON). A related program in another orphan disease is running and aiming for regulatory submission in the US in the very near future.

4Pharma’s role:
  • statistical contribution to regulatory meetings
  • data management collaboration with the customer and CRO
  • state-of-art statistical plan, analysis datasets and statistical analyses of the study
  • statistical contribution and joint writing of the study report and dossier
  • participation in the oral explanation before the CHMP conclusive meeting

Status: CHMP has recommended granting a marketing authorization for the product in the treatment of visual impairment in adolescent and adult patients with LHON.

Market: LHON is a severe form of vision loss caused by mitochondrial dysfunction. Prevalence of the disease is not well known but is estimated at 1/15,000 - 1/50,000 people worldwide. Affected patients, usually young and otherwise healthy, rapidly lose central vision and become bilaterally blind within a few months from the onset of symptoms. Although there is a chance for partial or even full spontaneous recovery, most patients remain permanently blind if un-treated. The mode of action of idebenone provides a clear biochemical and medical rationale and the clinical data demonstrate that vision of affected patients can substantially improve upon treat-ment with Raxone. This recommendation is a landmark in mitochondrial disease research world-wide and will undoubtedly spur further research in this direction.

Publications:
  • Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S, Bailie M, Atawan A, Chattopadhyay S, Schubert M, Garip A, Kernt M, Petraki D, Rummey C, Leinonen M, Metz G, Griffiths PG, Meier T, Chinnery PF: A randomized placebo-controlled trial of idebenone in Leber’s hereditary optic neuropathy. Brain. 2011; 134(9): 2677-2686.
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  • Mascialino B, Leinonen M, Meier T: Meta-analysis of the prevalence of Leber hereditary optic neuropathy mtDNA mutations in Europe. Eur J Ophthalmol. 2012; 22(3): 461-465.
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  • Rudolph G, Dimitriadis K, Büchner B, Heck S, Al-Tamami J, Seidensticker F, Rummey C, Leinonen M, Meier T, Klopstock T: Effects of idebenone on color vision in patients with leber hereditary optic neuropathy. J Neuroophthalmol. 2013; 33(1): 30-36.


Visual Health - Dry eye


Customers: Local biotechs and global pharmaceutical companies targeting to alleviate dry eye syndrome caused by a chronic lack of sufficient lubrication and moisture on the surface of the eye; the consequences of which range from subtle but constant irritation to inflammation of the anterior (front) tissues of the eye.

4Pharma’s role:
  • data management collaboration with the customers and CROs
  • state-of-art statistical plans, review of the plans, analysis datasets and statistical analyses for studies ranging from phase I to phase II (proof-of-concept)
  • statistical contribution and joint writing of study report(s)
  • participation in scientific advice meeting(s) with European Authority

Status: Latest phase II study results are under evaluation.

Market: According to ESCRS London, the global dry eye therapeutics market is forecast to be worth $5.47 (€4.91) billion in 2020 and significantly more competitive than it is today. Considering the current dearth of treatment options and improved diagnostic methods, there is still room for pipeline therapies. Despite the lower prevalence of dry eye in the U.S. than in some other countries, the dry eye market makes up approximately 63% of the U.S. ophthalmic market. In the last 10 years for dry eye, 14 companies have failed to secure FDA approval for their products, even though many have received approval in Europe and Asia. The roadblock in the U.S. is primarily caused by difficulties in performing dry eye trials. These are difficult to perform because dry eye is a range of conditions with different symptoms, and signs and symptoms do not always correlate. Patients can have a variety of systemic diseases, such that the population to be treated is heterogeneous. This has led to a focus of drug companies to cut their development costs by looking at repurposing existing drugs. Because inflammation has been discovered to be a key component of dry eye, there are a significant number of anti-inflammatory products in the dry eye pipeline, including steroidals, nonsteroidals and other anti-inflammatory drugs.
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