Date: 2017-12-08
Type of information: Product launch
Product name: Vyzulta™/Vesneo® (latanoprostene bunod - previously known as BOL-303259-X and NCX 116) )
Compound: latanoprostene bunod ophthalmic solution
Therapeutic area: Ophtalmological diseases
Action mechanism:
- prostaglandin analog. Latanoprostene bunod is a nitric oxide-donating prostaglandin F2-alpha analog. Upon instillation in the eye, latanoprostene bunod is rapidly metabolized to two actives: latanoprost acid, a prostaglandin analog which primarily works within the uveoscleral pathway to increase aqueous humor outflow, and butanediol mononitrate, which releases nitric oxyde (NO) to increase outflow through the trabecular meshwork and Schlemm's canal. Preclinical studies have shown that NO plays a role in controlling IOP in normal eyes by increasing aqueous humor outflow through the trabecular meshwork and Schlemm's canal. Studies have also demonstrated that patients with glaucoma have reduced levels of NO signaling in their eyes, providing a rationale for the therapeutic value of NO-releasing molecules for patients with open-angle glaucoma or ocular hypertension.
- In March 2010, Bausch + Lomb signed a worldwide licensing agreement with Nicox for latanoprostene bunod,
Company: Valeant Pharmaceuticals (Canada)
Disease:
- reduction of intraocular pressure (IOP) in patients with glaucoma or ocular hypertension
Latest news:
- • On December 18, 2017, Valeant Pharmaceuticals International's wholly owned subsidiary, Bausch + Lomb, a leading global eye health company, announced that it has begun distributing Vyzulta™ (latanoprostene bunod ophthalmic solution), 0.024% to U.S. wholesale pharmaceutical distributors. Vyzulta™ will be available to patients across the United States through their local pharmacies within the next few days.
- • On November 2, 2017, Valeant Pharmaceuticals International, Inc.'s wholly owned subsidiary, Bausch + Lomb and Nicox announced that the FDA has approved the New Drug Application (NDA) for Vyzulta™ (latanoprostene bunod ophthalmic solution, 0.024%). Vyzulta™ is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.
- The most common ocular adverse events include conjunctival hyperemia, eye irritation, eye pain and instillation site pain. Increased pigmentation of the iris and periorbital tissue and growth of eyelashes can occur.
- As a result of this approval, Nicox will receive $17.5 million from Bausch + Lomb and will make a $15 million payment to Pfizer under a previous license agreement.
Vyzulta™ Comprehensive clinical trials:
- - Vyzulta™ vs. Timolol Study: Non-Inferior & Superior to Timolol 0.5% (32% Mean Diurnal IOP Reduction)
The efficacy and safety of Vyzulta™ were evaluated in two randomized, multi-center, double-masked, parallel-group Phase 3 studies, APOLLO and LUNAR, comparing Vyzulta™ with timolol maleate ophthalmic solution 0.5% in subjects (N=831) with open-angle glaucoma or ocular hypertension. The primary objective of these studies was to demonstrate that the mean IOP reduction over 3 months of treatment with Vyzulta™once daily (QD) in the evening was non-inferior to timolol 0.5% twice daily (BID).
- A secondary objective was to demonstrate the superiority of Vyzulta™ QD to timolol 0.5% BID. In both studies, Vyzulta™ met the primary efficacy endpoint. Vyzulta™ also demonstrated significantly greater IOP lowering than timolol 0.5% throughout the day at 3 months of treatment resulting in a reduction in mean diurnal IOP of 32% from baseline.2,3,4 The most common ocular adverse events included conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%). No unexpected safety concerns were raised as a result of any of the ocular sign assessments or vital sign measurements.
Vyzulta™ vs. Latanoprost Study: Greater Mean IOP Reduction vs. Latanoprost
In the Phase 2 VOYAGER study, designed to identify the appropriate dose of Vyzulta™ for the reduction of IOP in addition to assessing safety and efficacy, 413 patients across 23 sites in the United States and Europe were randomized to receive either latanoprostene bunod (various concentrations) or Xalatan (latanoprost ophthalmic solution 0.005%) once a day in the evening for 28 days. Two of the four doses tested, including the FDA approved dose for Vyzulta™ 0.024%, showed greater IOP reduction compared with Xalatan (latanoprost ophthalmic solution 0.005%), with the differences reaching 1.23 mm Hg (p=0.005) for Vyzulta™. In addition, 68.7% of subjects treated with the FDA approved dose for Vyzulta™ 0.024%, compared to 47.5% of subjects treated with Xalatan (latanoprost ophthalmic solution 0.005%), achieved a mean diurnal IOP ?18 mm Hg (p<0.05).5
- 52-Week Safety Study: Vyzulta™ Reduced Mean IOP to 14.4 mm Hg in Subjects with Mean Low Baseline IOP of 19.6 mm Hg - The long-term safety of Vyzulta™ was assessed in JUPITER, a single-arm, multicenter, open-label Phase 3 study of one-year duration in Japanese subjects (N=130) with open-angle glaucoma (including normotensive, pigmentary and pseudoexfoliative glaucoma) or ocular hypertension. The efficacy endpoints of the JUPITER study were to evaluate the absolute IOP level and its reduction from baseline over a 52-week period. The mean baseline IOP in the study eye in the JUPITER study was 19.6 mm Hg. Treatment with Vyzulta™ resulted in a 22% mean reduction in IOP at Week 4 which was sustained through Week 52. Mean IOP was 14.4 mm Hg at Week 52 representing a 26% reduction from baseline in the study eye.6 The most common ocular adverse events were conjunctival hyperemia, growth of eyelashes, iris pigmentation, blepharal pigmentation, eye irritation, and eye pain.
- 24-hour IOP Lowering Study: Vyzulta™ Demonstrated Better 24-hour IOP Control than Timolol. Another study, CONSTELLATION, compared the effect of Vyzulta™ dosed QD with timolol maleate ophthalmic solution 0.5% dosed BID in reducing IOP measured over a 24-hour period in subjects with open-angle glaucoma or ocular hypertension (N=25). The results of this randomized, single-center, open-label, 2-month crossover study demonstrated that Vyzulta™ lowered IOP over 24-hours, with a significantly greater nocturnal IOP reduction vs. timolol (p<0.004). The study also compared ocular perfusion pressure (OPP) in Vyzulta™-treated subjects vs. timolol-treated subjects over a 24-hour period. Vyzulta™ improved daytime OPP vs. baseline (p<0.001) and nocturnal OPP vs. timolol 0.5% (p=0.01).7
- • On August 7, 2017, Valeant Pharmaceuticals announced it has received a Complete Response Letter (CRL) from the FDA regarding the New Drug Application (NDA) for latanoprostene bunod ophthalmic solution, 0.024% for patients with open angle glaucoma or ocular hypertension. The CRL from the FDA refers to a Current Good Manufacturing Practice (CGMP) inspection at Bausch + Lomb’s manufacturing facility in Tampa, Fla. Last year, the FDA had already released a CRL raising concerns to GMP at this facility (see below)
- • On March 20, 2017, Bausch + Lomb and Nicox announced that the FDA has set a PDUFA date of August 24, 2017 for its decision on the New Drug Application (NDA) for latanoprostene bunod ophthalmic solution, 0.024%.
- • On February 27, 2017, Bausch + Lomb, and Nicox announced the resubmission of a New Drug Application to the FDA seeking approval for latanoprostene bunod ophthalmic solution, 0.024%.for patients with open angle glaucoma or ocular hypertension .
- • On July 22, 2016, Valeant Pharmaceuticals announced it has received a Complete Response Letter (CRL) from the FDA regarding the New Drug Application for latanoprostene bunod ophtalmic solution, 0.024% for patients with open angle glaucoma.
- The concerns raised by the FDA pertain to a Current Good Manufacturing Practice (CGMP) inspection at Bausch + Lomb's manufacturing facility in Tampa, Florida where some deficiencies were identified by the FDA. The letter did not identify any efficacy or safety concerns with respect to the NDA or additional clinical trials needed for the approval of the NDA for latanoprostene bunod ophthalmic solution, 0.024%. Valeant intends to meet with the FDA as soon as possible to work on a resolution and address these concerns.
- • On September 22, 2015, Valeant Pharmaceuticals announced that the FDA has accepted for review its New Drug Application (NDA) for Vesneo™ (latanoprostene bunod ophthalmic solution 0.024%) for patients with open angle glaucoma or ocular hypertension. If approved, Vesneo™ will be the first nitric oxide donating prostaglandin receptor agonist available for the above indication. The FDA has set an action date of July 21, 2016 to complete its review, as per the Prescription Drug User Fee Act (PDUFA).
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization: 2017-11-02
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
