IN BRIEF• Ampio Pharmaceuticals Inc. announced positive results of the OptimEyes trial of its oral Optina drug for diabetic macular edema. In a subgroup of patients based on body-mass index, 53 percent of those who were unresponsive to existing intravitreal injections showed a 6.2 letter improvement in visual acuity over three months; the remaining 47 percent, who were unable or unwilling to have intravitreal injections, showed a 3.1 letter improvement over the same period.• Ophthotech Corp. has completed patient recruitment for its first Phase III trial of its Fovista anti-PDGF drug in combination with ranibizumab (Lucentis) in wet age-related macular degeneration. The company expects to complete patient recruitment in the second Phase III trial of combination Fovista-Lucentis by the end of the third quarter this year. Ophthotech expects topline data from both trials to be available in 2016. Meanwhile, a third Phase III trial investigating Fovista in combination with aflibercept (Eylea) or bevacizumab (Avastin) is currently recruiting patients. • Spark Therapeutics Inc. acquired exclusive rights to license Clearside Biomedical Inc.’s microinjector technology to deliver gene therapies to the back of the eye. Under the agreement, the companies will explore the feasibility of using Clearside’s microinjector technology to deliver viral vectors to the choroid and the retina through the suprachoroidal space. • ThromboGenics NV is evaluating ocriplasmin (Jetrea) as a potential treatment for retinal vein occlusion (RVO). The new research will build on earlier ThromboGenics Phase IIa data pointing out the potential of ocriplasmin for the treatment of peripheral arterial occlusions, the company says. With this new vitreoretinal project, ThromboGenics aims to demonstrate the potential of using locally delivered ocriplasmin for lysing the blood clots responsible for RVO in diabetic macular edema. |
“The proposed FDA guidance on repackaging of biologics is very strict and will greatly curtail use of Avastin in the clinic,” says Geoffrey Emerson, MD, PhD, chair of the ASRS Federal Affairs Committee. “The guidance as written makes it very difficult to order, receive and administer Avastin in the time allowed by the FDA.” That could force retina specialists to use the more costly Lucentis (ranibizumab, Genentech) or Eylea (aflibercept, Regeneron) instead.
The FDA’s proposed rules would restrict beyond-use dates (BUDs) for traditional compounders and outsourcing facilities. Compounders may continue to repackage bevacizumab for ophthalmic use, but the proposed BUDs would make it “extremely difficult” for ophthalmologists to order and store bevacizumab for office use, states an ASRS analysis of the rules. ASRS is urging the FDA to set aside the proposed BUDs and focus instead on the science.
For traditional compounders, the proposed BUDs are up to four hours or whatever the labeling states the allotted time within which the opened product should be used, whichever is shorter; or up to 24 hours if microbial challenge studies have demonstrated that microbial growth of the repackaged formulation will not reach a harmful level within the BUD period. Traditional compounders will still need a patient-specific prescription to dispense bevacizumab.
For outsourcing facilities, BUDS would be the same with one additional mandate: five days or less or the expiration date of the product being repackaged, whichever is shorter—provided the outsourcing facility performs compatibility studies on its repackaging system to verify product integrity.
The challenge with bevacizumab relates to its off-label use for age-related macular degeneration and diabetic retinopathy. Ranibizumab and aflibercept come in glass vials with an expiration date two years after their manufacture; bevacizumab comes in 100- or 400-mg vials, which are used for intravenous infusion to treat colon cancer, Dr. Emerson explains. For use in the eye, compounders and outsourcing facilities must repackage the drug must from the manufacturer’s glass vial into smaller vials or plastic syringes.
“According to the proposed FDA guidance, the BUD for repackaged Avastin will be a maximum of one day for a traditional compounding pharmacy and five days for an outsourcing facility,” Dr. Emerson says. “The proposed BUDs are very short compared to the standard practice that has been in place for the past 10 years, with BUDs of typically three to six months.”
The proposed BUDS would make it impossible for retina specialists to perform 14-day sterility testing on the repackaged bevacizumab. “Many retina specialists insist that sterility testing is required for patient safety,” Dr. Emerson says. “Second, the logistics of ordering, receiving and administering Avastin will be extremely rushed and complex given the proposed one- and five-day BUDs, and it may be impossible to have repackaged Avastin available for use on Monday or Tuesday depending on whether a compounding pharmacy or outsourcing facility repackage and ship drugs during the weekend.”
The comment period for the proposed rule change closed in May, but the process of issuing the final rule could take months.
21st Century Cures Would Restore NIH, NEI Funding
Legislation that would restore funding to the National Institutes of Health and the National Eye Institute is moving through Congress with uncharacteristic bipartisan support.The House Energy and Commerce Committee in May approved the 21st Century Cures Act by a 51-0 vote. The act would increase overall NIH funding $1.5 billion a year over each of the next three fiscal years and provide an additional $10 billion over the next five years for the NIH Innovation Fund.
“A rising tide lifts all boats, so increased NIH funding ideally would mean additional funding for the institutes and centers,” James Jorkasky, executive director of the National Alliance for Eye and Vision Research. The Innovation Fund would target emerging scientists, high-risk, high-reward research and big-ticket infectious disease research, Mr. Jorkasky says. “There’s opportunity there for vision researchers,” he says.
Several hurdles remain before the funding appears. The full House has to vote on the bill, and the Senate, where the Health Education and Labor and Pensions Committee is coordinating legislation with the House committee, must also pass it. Then there’s the matter of actually getting the appropriations from Congress; 21st Century Cures is merely an authorization, not an appropriation.
Robert Eugene Anderson, MD, PhD, director of research at Dean McGee Eye Institute at the University of Oklahoma and a longtime advocate for vision research with the Association for Research in Vision and Ophthalmology, says the potential for more medical research funding would reverse a devastating trend over the past decade.
“As far as the NEI is concerned, we’ve gone from more than 1,200 to a little more than 1,000 R01 research grants today; that’s about a 15 percent cut,” Dr. Anderson says. R01 is an original NIH grant category that allows the investigator to define the focus of the research. RS
