SUBSPECIALTY NEWS

Ophthotech Outlines Drug Development Program

Company targets both wet and dry AMD.

■ Armed with $97.2 million of new funding from stock sales and venture capital, Ophthotech (New York, NY) recently announced an ambitious drug development program aimed at providing new therapies for treating both the wet and dry forms of AMD.

With the new financing now in hand, Ophthotech plans to expand its lead product candidate, the anti-PDGF agent Fovista, beyond its current pivotal phase 3 trial in wet AMD, while also advancing a second product candidate Zimura, an inhibitor of complement factor C5, in both wet and dry AMD.

The current Fovista phase 3 program consists of three large clinical trials to evaluate the safety and efficacy of the anti-PDGF therapy in combination with the proven anti-VEGF agents ranibizumab (Lucentis, Genentech), aflibercept (Eylea, Regeneron) and bevacizumab (Avastin, Genentech). The company expects to enroll a total of 1,866 patients in the three trials in more than 225 centers worldwide and to have initial, top-line data from the Fovista phase 3 clinical program available in 2016. In the combination trials, the two drugs are administered by separate injections. This is a point of difference with Regeneron, which has co-formulated its anti-PDGF and aflibercept combination as a single injection for a recently announced early-stage clinical trial.

The Fovista program expansion will include clinical trials of Fovista in combination with anti-VEGF therapy for the treatment of anti-VEGF-resistant wet AMD patients and to assess possible reduction of treatment burden in wet AMD therapy.

Ophthotech also plans to initiate a clinical trial to investigate the effect of Fovista in potentially inhibiting the formation of subretinal fibrosis in wet AMD patients treated with anti-VEGF therapies. Ophthotech says studies have shown that subretinal fibrosis is associated with severe vision loss in wet AMD patients. These trials are scheduled to begin this year. In addition, the National Eye Institute is scheduled to conduct a clinical trial with Fovista in von Hippel-Lindau disease starting in 2014, and the company is planning to initiate a clinical trial of Fovista in proliferative vitreoretinopathy in 2015.

In the Zimura program, the company is expected to advance to a phase 2/3 clinical trial for treatment of geographic atrophy in late 2014 or early 2015. In addition, a phase 2 clinical trial is planned for Zimura and Fovista in combination with anti-VEGF therapy for the treatment of anti-VEGF-resistant wet AMD patients believed to have complement-mediated inflammation. This trial is scheduled to begin in 2015.

“Our plan calls for 10 clinical trials ongoing or initiating in 2014 and 2015, and data expected to begin in 2015,” said David Guyer, MD, CEO of Ophthotech.

Compounder Linked to Fungal Endophthalmitis

CDC study finds 47 cases since 2011.

■ A multi-state investigation conducted by the Centers for Disease Control (CDC) and reported in the February 2014 issue of Emerging Infectious Diseases found a total of 47 cases of fungal endophthalmitis linked to tainted Brilliant Blue G (21 cases) and triamcinolone acetonide (26 cases) dispensed by a single compounding pharmacy. All of the cases were reported since 2011 and all involved invasive ocular procedures.

The tainted products were traced to Franck’s Compounding Lab in Ocala, FL, which has since gone out of business. Of the 40 case patients for whom data was available, 39 lost vision.

The study noted that Brilliant Blue G is not an FDA-approved drug and that all of it comes from compounding pharmacies.

The CDC cautions that “clinicians should be aware that the availability of a compounded medication in the United States is not a guarantee of its quality or of FDA approval. Disclosure of a medication’s FDA approval status should be encouraged at all stages of purchase and use.”

The CDC stated that having this information available could help clinicians “to make informed decisions about the medications they purchase for patient use and to educate patients about the status of medications to which they are exposed. Maintenance of the safety and integrity of sterile compounded drugs in the United States demands a thorough review and improvement of compounding pharmacy regulatory practices.”

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QLT Has Promising LCA and RP Data

Majority of patients respond to oral treatment.

■ QLT, Inc., (Vancouver, BC) has announced positive preliminary results from its international, multicenter, phase 1b clinical trial of repeated treatments of oral QLT091001 in subjects with Leber congenital amaurosis (LCA) or retinitis pigmentosa (RP) due to inherited genetic mutations in retinal pigment epithelium (RPE65) or lecithin:retinol acyltransferase (LRAT).

The open-label trial is an extension study in which LCA or RP subjects with RPE65 or LRAT mutations, who had been treated with a single course of QLT091001 in the company’s completed phase 1b study, received up to three seven-day courses of QLT091001 to assess visual outcomes and safety following retreatment.

QLT said preliminary results of this phase 1b study showed clinically meaningful improvements in visual fields (VF) and visual acuity (VA). To date, 19 of 27 subjects had an increase in VF retinal area from baseline of at least 20% in at least one eye at two consecutive visits within six months from the start of any QLT091001 treatment course. In addition, the company said 70% of subjects had an increase in VA from baseline of at least 5 letters in at least one eye at two consecutive visits within six months from the start of any treatment course.

Dosing in the study is now completed and subject follow-up is ongoing. The final clinical data, including duration of response and other evaluations, are anticipated for release in the third quarter of 2014.

Post-marketing Study to Evaluate Jetrea

Large trial to focus on real-world usage.

■ ThromboGenics, NV, (Leuven, Belgium) said it plans to initiate a US phase 4 study of Jetrea (ocriplasmin) called The Ocriplasmin Research to Better Inform Treatment (ORBIT) study, designed to generate further data on the real-world use of Jetrea.

The ORBIT study will recruit 1,500 patients with symptomatic vitreomacular adhesion (VMA) or vitreomacular traction (VMT) across 120 retina centers in the United States. The prospective, observational study will assess clinical outcomes and safety of Jetrea administered in a real-world setting by assessing both anatomical and functional outcomes.

ThromboGenics acknowledges the Jetrea launch has been somewhat disappointing, but the company has ascribed the shortfall primarily to lack of a permanent J code, which the drug now has received. The company also recently said it is exploring strategic alternatives to improve sales of Jetrea.

The study will look at a number of parameters including resolution of VMA, full thickness macular hole closure, changes in visual acuity, and occurrence and time to vitrectomy.

The study will also monitor adverse drug reactions and changes from baseline in ocular signs and symptoms across time. ThromboGenics says these data will further characterize the efficacy and safety profile of the product and provide data complementary to those from the phase 3 clinical program and its first year on the market.

The trial will follow patients for up to 12 months after treatment with Jetrea. The ORBIT study is expected to start recruiting patients this month with completion due in mid-2016.

Patrik De Haes, PhD, CEO of ThromboGenics, comments: “The start of the ORBIT study in the US reflects ThromboGenics’ commitment to gain further knowledge on the real world use of Jetrea. We feel it is important with such a novel treatment option as Jetrea to conduct a significant post-marketing study to assess which patients gain the greatest benefit from the first pharmacological option designed for the treatment of symptomatic VMA/VMT.”