Three Pivotal Fovista Trials Set
Ophthotech studies to involve 1,866 patients.
BY JERRY HELZNER, SENIOR EDITOR
▪ Ophthotech has registered three large pivotal phase 3 studies with the FDA to determine whether its anti-platelet derived growth factor (PDGF) drug Fovista used in combination with anti-VEGF therapy can prove more effective than anti-VEGF monotherapy in treating wet AMD. In a 449-patient phase 2b trial, the combination of Fovista and ranibizumab (Lucentis) demonstrated better efficacy and a greater duration of response than ranibizumab monotherapy.
The company will recruit a total of 1,866 treatment-naïve patients to participate in the three trials, with 622 patients designated for each of the studies. Two identical trials will each compare 311 patients treated with 1.5 mg Fovista and 0.5 ranibizumab intravitreal injections to 311 receiving 0.5 mg ranibizumab monotherapy. Both trials are already recruiting patients.
The third trial, which is not yet recruiting, will similarly compare a 1.5 mg Fovista injection and 2 mg aflibercept (Eylea) or 1.5 mg Fovista and 1.35 mg bevacizumab (Avastin) combination to aflibercept or bevacizumab monotherapy. The primary endpoints will be improvement in visual acuity at 12 months and safety. The trials will be conducted over a 24-month period with final data expected to be available in July 2016.
Ophthotech recently announced a public stock offering intended to raise $100 million. Much of this money, along with $175 million in new venture capital financing, will go to fund the three largescale studies.
|TIPS OF THE MONTH
Avoiding Malpractice Claims
Six preventive steps you can take.
Malpractice claims are traumatic events that can cause feelings of anger and guilt, and even lead to depression. Ophthalmic Mutual Insurance Company and defense lawyers offer these steps to reduce ophthalmologists’ malpractice risks.
1 Have a “bulletproof” informed consent form. You can go to www.omic.com for examples.
2 Never allow anyone to alter a patient record after the fact.
3 Don’t jump to a diagnosis just because it “looks” like something you’ve seen before.
4 Never attempt to re-use a single-use instrument.
5 Always make a same-day follow-up call to your surgical patients.
6 Stay current with new studies and safer techniques. For example, one study suggested wearing a mask and gloves when giving intravitreal injections.
▪ ThromboGenics provides Jetrea update. ThromboGenics recently reported that Jetrea (ocriplasmin), which was approved by the FDA for the treatment of symptomatic vitreo-macular adhesion (VMA) late last year, recorded $16.6 million in US sales through June 30. Jetrea was launched in the United States in mid-January.
ThroboGenics also reported data from a phase 2a study indicating that Jetrea has the potential to resolve VMA in patients with wet AMD. In 100 patients with both wet AMD and VMA, the VMA was resolved in 24% of those who received a Jetrea injection, but in only 12% of the the sham group. The full study results will be presented at the AAO meeting in November.
In other news from ThromboGenics, the company has signed a collaboration and license agreement with Bicycle Therapeutics to develop and commercialize novel drugs inhibiting a specific target for the treatment of DME. ThromboGenics intends to develop therapeutics based on Bicycle’s bicyclic peptides, which inhibit a target involved in vascular permeability. The company says selective inhibition of this target represents a new approach that offers the potential to improve the treatment of DME.
Promising Data for Dry AMD Drug
Roche releases phase 2 MAHALO results.
▪ Roche announced positive phase 2 results from the MAHALO study demonstrating that lampalizumab (also referred to as anti-factor D) showed a 20.4% reduction rate in the area of geographic atrophy at 18 months in patients with advanced dry AMD.
The MAHALO phase 2 data also showed no unexpected or unmanageable serious adverse events associated with lampalizumab. These data were presented at the recent annual meeting of the American Society of Retina Specialists.
MAHALO is the first study to show a beneficial treatment effect with a complement inhibitor in geographic atrophy. Efficacy of lampalizumab was observed in the monthly group beginning at month six and was maintained through month 18.
“The phase 2 results are encouraging for patients with geographic atrophy, a major vision-impairing disease where there is a great need for treatment options,” said Richard Scheller, PhD, Head of Genentech Research and Early Development. “We are continuing to investigate our emerging biomarker strategy to identify people who would be appropriate candidates for treatment with lampalizumab.”
In a specific sub-population of GA patients treated monthly with lampalizumab that were identified using exploratory biomarkers, the GA progression rate was decreased by 44% at 18 months. In the subset of patients positive for the exploratory biomarkers who presented with better vision (20/50 to 20/100), progression of the GA area was reduced by 54% at 18 months when treated with monthly lampalizumab. From the patient samples collected in the MAHALO study, 57% of patients were positive for the exploratory biomarkers. More information on the biomarkers will be shared at a future medical congress.
▪ The following correction is noted for the article “Pharmacodynamics Of Visual Cycle Modulation In the Treatment of GA” in the September issue of Retinal Physician (Mata NL et al. 2013;10 (7):22-25):
• The subtitle should read “Emerging data from clinical studies demonstrate the biological activity of emixustat in the retina.” The original wording of the subtitle was generated by the editors of Retinal Physician and not the authors of the article.
Retinal Physician regrets the error.
▪ AMA survey finds private practice still predominates. New data on physician practice arrangements compiled in the AMA “Policy Research Perspectives” series demonstrated that reports of a surge in physician employment by hospitals may be overstated. The AMA survey conducted in 2012 found that 53.2% of physicians were self-employed and 60% worked in practices wholly owned by physicians. This represents a small decrease from earlier studies.
Although the AMA survey gave no specific figures on physician self-employment for ophthalmology, it reported that 71.9% of surgical subspecialists held ownership stakes in their practices. This is the highest level of ownership for any survey category. In contrast, only 37.3% of pediatric physicians and 38.4% of emergency medicine doctors held ownership stakes.
▪ EU approves Eylea for CRVO indication. Regeneron Pharmaceuticals said Eylea (aflibercept) has been approved for the treatment of macular edema secondary to CRVO.
Eylea was approved in the United States for the treatment of wet AMD in 2011 and for macular edema following CRVO in September 2012. Eylea has also been approved in Europe, Japan, Australia and several other countries for treatment of wet AMD.
▪ Mazzo joins Neurotech. Neurotech Pharmaceuticals, a Rhode Island biotechnology company developing proprietary sustained-release therapies for chronic retinal disease, has appointed ophthalmic industry veteran James Mazzo as executive chairman.
Mr. Mazzo, the former CEO of Abbott Medical Optics, is an operating partner at the venture capital firm Versant Ventures and was recently named chairman and CEO of AcuFocus, a Versant portfolio company. As executive chairman, Mr. Mazzo will engage with the Neurotech team to advance the company’s novel technology platform through the clinical development stage toward market commercialization.
Neurotech’s patented core technology platform, Encapsulated Cell Technology (ECT), is a genetically engineered implant that enables the continuous delivery of protein drugs directly into the vitreous of the eye. The company says it has demonstrated that a single living ECT implant can treat a diseased retina for two years or more.
Musculoskeletal Disorders Plague Retinal Surgeons
Doctors should take preventive measures.
BY RENÉ LUTHE, SENIOR ASSOCIATE EDITOR
▪ Musculoskeletal disorders (MSD) and pain are the unwelcome companions of most vitreoretinal surgeons, according to research presented at the recent American Society of Retina Specialists annual meeting.(1)
Researchers Hemang K. Pandya, MD, and Asheesh Tewari, MD, sent a 19-question electronic survey to all ASRS members and received 85 responses from August 2012 to November 2012. Seventy-three of 85 responding vitreoretinal surgeons reported MSD pain, with 37 of the 85 having been specifically diagnosed. Of the subset reporting established MSD, the authors also listed their diagnoses (Table).
Of the respondents with established MSD, 67.6% (25 of 37) believe their condition is linked to performing vitreoretinal surgery. Among this group, 81.1% have received medical treatment, with 13.5% undergoing surgical intervention. Approximately 16% reported having reduced or ceased performing vitreoretinal surgery due to their MSDs.
“Early detection of musculoskeletal problems is paramount,” says co-author Dr. Pandya. “Our study found that pain in younger vitreoretinal surgeons may be a precursor to an established musculoskeletal disorder in the older surgeon. As the old adage states, prevention is the best cure.” However, he notes, many vitreoretinal surgeons are not taking the appropriate measures to prevent MSDs. He concludes that focusing on improving ergonomic designs in the office, laser suite and operating room are critical to avoiding MSDs.
|TABLE: THE MSDS OF VITREORETINAL SURGEONS
|Spinal disc herniation .............................................||21.2%|
|Chronic back pain .................................................||15.3%|
|Degenerative joint disease/osteoarthritis .................||10.6%|
|Carpal tunnel syndrome .........................................||5.9%|
|Rotator cuff tendonitis ...........................................||3.5%|
|Ulnar neuropathy ..................................................||2.4%|
1. Pandya HK, Tewari A. Musculoskeletal disorders in vitreoretinal surgeons. Poster presented at: American Society of Refractive Specialists 31st Annual Meeting. Toronto; August 24-28, 2013.
▪ Kala explores topical drug for wet AMD. Kala Pharmaceutical, headquartered in Waltham, MA, is conducting preclinical studies of a topical, mucosal-penetrating formulation of a small molecule receptor tyrosine kinase inhibitor as a potential treatment for a broad range of eye diseases, including wet AMD. The company says it believes mucosal barriers have been largely overlooked as a limitation for drug efficacy.
▪ Argus II qualifies for added Medicare payments. Second Sight Medical Products said its Argus II Retinal Prosthesis System has won CMS approval for both a new technology add-on payment (inpatient setting of care) and a transitional pass through payment (outpatient setting of care) beginning October 1. These payments are designed to support timely access to innovative technologies for Medicare beneficiaries.
According to the CMS, cases involving the Argus II System eligible for new technology add-on payments under the Medicare Inpatient Prospective Payment System will be identified by a new ICD-9-CM procedure code 14.81. Additionally, CMS has also established a transitional pass through payment for Argus II. This payment will be available to all hospital outpatient facilities and ASCs that perform this procedure for Medicare beneficiaries, and will be identified by the 0100T CPT code.
“This news greatly facilitates access to the Argus II for Medicare beneficiaries, regardless of the setting of care in which the system is provided,” said Brian Mech, VP of Business Development at Second Sight.
▪ Orphan drug status for RP therapy. Dompé, a drug-development company based in Milan, Italy, said its investigational drug for the treatment of retinitis pigmentosa (RP) and based on the recombinant human nerve growth factor (rhNGF), has been granted orphan drug designation by the FDA. The drug had several months earlier been awarded similar status in the European Union.
Retinal Physician, Volume: 10 , Issue: October 2013, page(s): 8 - 11