H2R
2 weeks ago
UK Approval PR
ISELIN, N.J., July 08, 2024 (GLOBE NEWSWIRE) -- Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company focused on development and commercialization of ONS-5010/LYTENAVA™ (bevacizumab-vikg; bevacizumab gamma) for the treatment of retina diseases, today announced that the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for LYTENAVA™ (bevacizumab gamma), an ophthalmic formulation of bevacizumab for the treatment of wet AMD in the UK. LYTENAVA™ (bevacizumab gamma) is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in the EU and UK.
Professor Tim Jackson, PhD, FRCOphth, Consultant Ophthalmic Surgeon, King's College Hospital and Professor of Retinal Research, King’s College London, commented, “We have waited a long time for a brand of bevacizumab that is authorized for eye use, and it is good news that LYTENAVA™ has now entered the market. This occurs subsequent to Outlook Therapeutic's clinical trial meeting its endpoint. To date, many ophthalmologists have been hesitant to use an off-label bevacizumab, when licensed products are available. We value being able to utilize products that meet the standards required for marketing authorization. Additionally, a well-controlled pharmaceutical manufacturing operation will allay concerns that compounding pharmacies increase the risk of rare but potentially devastating endophthalmitis.”
This approval comes after Outlook Therapeutics was recently granted Marketing Authorization for LYTENAVA™ (bevacizumab gamma) by the European Commission for the same therapeutic indication. The Marketing Authorization Application (MAA) submission to the MHRA was completed under the new International Recognition Procedure (IRP), which allows the MHRA to rely on a positive opinion by the European Medicines Agency’s CHMP concerning an application for granting marketing authorization for the same product in the EU in the MHRA’s authorization decision.
“We are pleased to receive UK approval on the heels of marketing authorization in the EU for LYTENAVA™ (bevacizumab gamma). This milestone achievement is the final regulatory step towards our expected commercial launch in the EU and UK in the first calendar quarter of 2025. Our team continues to make a concerted effort to bring to the UK market the first and only authorized ophthalmic bevacizumab for the treatment of wet AMD. We are grateful to all the patients, researchers, clinical sites and the MHRA for the research, drug development, and regulatory efforts that led to this approval,” commented Russell Trenary, President and Chief Executive Officer of Outlook Therapeutics.
Jedd Comiskey, Senior VP – Head of Europe for Outlook Therapeutics, added, “MHRA approval represents a very important milestone for Outlook in the execution of our commercial launch plans for LYTENAVA™ (bevacizumab gamma) in the UK. Our team continues to work hand in hand with our commercialization partner, Cencora, to support our launches in the EU and UK anticipated in the first calendar quarter of 2025, and we are looking forward to an exciting year ahead.”
As part of a multi-year planning process, Outlook Therapeutics entered a strategic collaboration with Cencora (NYSE: COR) (formerly AmerisourceBergen) to support the commercial launch of LYTENAVA™ globally following regulatory approvals.
Cencora will provide comprehensive launch support in the EU and the UK including pharmacovigilance, regulatory affairs, quality management, market access support, importation, third-party logistics (3PL), distribution and field solutions. The collaboration and integrated approach is designed to support market access and efficient distribution of LYTENAVA™ to benefit all stakeholders, including retina specialists, providers and patients.
“We have been working closely with Outlook Therapeutics to develop and execute a global launch strategy and are thrilled to help them bring this therapy to market in the UK and the EU,” said Cencora’s John W. Arena, interim president of Global Pharma Services and senior vice president of Enterprise Strategy & Solutions. “We will continue to leverage our infrastructure and pharmaceutical services to support a successful commercial launch of LYTENAVA™ and ensure healthcare providers have timely and reliable access to the therapy.”
Best of luck with your investments!
thermo
2 weeks ago
Outlook Therapeutics (OTLK) / BTIG Research / JULY 8, 2024
NDR Recap: We See a Straight Path to BLA Resubmission ~YE24. NORSE EIGHT Enrollment Completion Later in 3Q24 Should Confirm the Timeline.
WHAT YOU SHOULD KNOW:
We hosted meetings this past week with OTLK mgmt where discussions focused on the remaining steps to BLA resubmission, pre-commercial efforts in Europe (EU marketing authorization received in May, launch expected in calendar 1Q25), and how compounded bevacizumab could fall out of favor when LYTENAVA (fka ONS-5010) becomes commercially available. The market opportunities for LYTENAVA in the US and Europe are both large and currently correspond to ~3.5 million and ~2.8 million compounded bevacizumab injections per year, respectively. Since compounded bevacizumab is not held to the same strict regulatory standards as an approved ophthalmic formulation, we think liability associated with off-label use could become more of a concern when a more carefully regulated product (i.e., LYTENAVA) becomes commercially available (Exhibit 1). We also recognize that LYTENAVA's recent marketing authorization in Europe de-risks the upcoming CMC review by the FDA. Remaining steps to BLA resubmission look straightforward to us, with NORSE EIGHT enrollment completion expected later in 3Q24, followed by topline data in 4Q24, BLA resubmission ~YE24, and potential US launch in 2H25.
NORSE EIGHT mirrors the first 3 months of NORSE TWO. NORSE EIGHT involves the same doses of ONS-5010 and ranibizumab as the first 3 months of the previously completed NORSE TWO trial, which showed ONS-5010 numerically outperforming ranibizumab on BVCA as early as 30 days and greater separation at later timepoints (Exhibit 2). We currently assume a 90% probability of success.
NORSE EIGHT in detail, is a 3mo non-inferiority study of ONS-5010 vs. ranibizumab with an abbreviated 2mo primary efficacy endpoint (BVCA; 3.5 letter non-inferiority margin) that plans to enroll ~400 treatment-naive wet AMD patients. Mgmt. previously confirmed that the FDA did not take issue with the design or results of NORSE TWO but rather with the fact that the initial ONS-5010 BLA contained 1 pivotal efficacy trial instead of 2. The FDA has provided written agreement for NORSE EIGHT under an SPA, which provides reassurance that the trial will be sufficient as a second study to support potential approval. Enrollment is underway and is proceeding at an encouraging pace (30% complete as of 5/15/24; target enrollment is 400 treat). Since >90% of sites were active at the start of April (vs. ~50% in March), we see a good chance of the enrollment proceeding in a typical "hockey stick" trajectory from here.
EU approval helps to provide some confidence around the CMC package. Mgmt. noted that both the EMA and the FDA received the same CMC package for review. According to mgmt., the questions around CMC included in the CRL were similar to those often included in information requests during a drug’s review process. Furthermore, the prescriptive nature of the CMC questions supports straightforward resolution of these open items. Mgmt. is continuing to meet with the FDA in scheduled Type C and D meetings to go over the CMC data and has signaled confidence in the ability to resolve the open CMC questions by the time of the expected BLA resubmission (YE24). We think the ongoing engagement with the FDA and approval in the EU based on the same CMC data help remove risk around CMC, and do not see CMC issues as a large concern going forward.
Europe represents the second-largest market for wet AMD, and we expect pricing and reimbursement advantages for LYTENAVA similar to those in the US. While the US is the bigger market opportunity in Outlook’s mind (roughly 3x the size of the Europe opportunity), the overall dynamics driving off-label bevacizumab use are similar. Off-label bevacizumab represents ~40% of the injections in the EU compared to ~50% in the US. In addition, although prices are generally lower in Europe than in the US, branded and biosimilars are still priced at premiums multiples higher than off-label bevacizumab, providing a wide window for Lytenava. Mgmt.’s decision to target Germany and the UK first in pricing conversations make sense to us, given these two countries have the highest prices for anti-VEGFs and are associated with tougher pricing processes. If Lytenava can benefit from the higher ceiling on price in these markets, we think this could act as a good benchmark for other Europe countries as well. Approval in the UK is expected in 3Q24 and mgmt. is planning to launch in both Germany and the UK in 1Q25.
Compounded bevacizumab likely falls out of favor if ONS-5010 is approved by the FDA. OTLK mgmt. believes that compound pharmacists that choose to continue making compounded bevacizumab after ONS-5010 becomes commercially available could put their entire operations at risk. Laws and regulations aside, high particulate counts, less than ideal storage conditions, and lack of reachable/extractable testing are well-known shortcomings of compounded bevacizumab that ONS-5010 significantly improves upon with higher manufacturing standards. Management has also noted that repackaging leads to protein shearing and reaggregation, which likely is another source of high batch-to-batch variability in current off-label bevacizumab use. Interestingly, OMIC (Private), the largest ophthalmic medical malpractice insurer in the US, has indicated that if a patient is being treated with off-label bevacizumab in one eye, they are not going to provide medical malpractice coverage for the second eye. OTLK is also optimistic that state pharmacy boards and the ethics committees at large academic medical centers (many have their own compound bevacizumab operations, currently) will be motivated to seek alignment with current regulations.
Compounding will become a question of supply, not just demand once ONS-5010 is available. Only two compound pharmacists, Fagron (FSE: FAGR.BR, Not Rated) and Leiters (Private), obtain bevacizumab via distributors. These two pharmacies are unable to ramp up production meaningfully if needed due to the thin margins on bevacizumab. Other compound pharmacists, such as Pine (Private) (responsible for producing almost half of all off-label bevacizumab injections), receive bevacizumab through drop-shipments from physicians. If physicians choose not to ship IV bevacizumab to compounders, we expect the manufacture of off-label bevacizumab as a whole will start to decrease. We are already starting to see physicians shift away from off-label bevacizumab. Mgmt. shared that KOLs are already starting to acknowledge the shortcomings of off-label bevacizumab in reaching ophthalmologic standards. With greater education and increased awareness, mgmt. expects more physicians will opt for an approved product and stop facilitating the manufacture of off-label bevacizumab.
Real-world quality of compounded bevacizumab appears much lower than what was studied in the CATT trial. A highly referenced study on compounded bevacizumab's efficacy was conducted by the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) Research Group, which enrolled 1,185 patients with wAMD to compare compounded bevacizumab and ranibizumab. The study found that ranibizumab and compounded bevacizumab are equivalent in efficacy, although endophthalmitis was observed with compounded bevacizumab at two times the rate vs. ranibizumab (0.07% vs. 0.04%, respectively). Furthermore, the rate of serious systemic AEs, primarily hospitalizations, was higher among bevacizumab-treated patients than among ranibizumab-treated patients (24.1% vs. 19.0%, p=0.04). There are many who argue that the results were generated from batches of compounded bevacizumab that were of higher quality than what is typically encountered in the real-world setting. On this point, an article was published in JAMA in 2014 detailing how variable the quality of compounded bevacizumab can be in the real-world setting.
Real-world bevacizumab contains lower drug concentrations, leaving efficacy on the table. In the 2014 JAMA study that looked at protein concentration in samples taken from 11 different compounding pharmacies in the US, all samples were found to have protein concentrations lower than the bevacizumab control taken from Genentech (RHHBY, Not Rated). 81% of these samples (n=17/21) had significantly lower protein concentrations with a mean of 22.2mg/mL across compounded pharmacy samples (vs. 25mg/mL for Genentech's sample, p
H2R
1 month ago
And now 60 recruiting sites (out of 60 planned!)
The latest (last?) one is Oakland, California, United States, 94611
The investor's presentation, slide 18, indicates OTLK was planning on 60 recruiting sites:
400 treatment naïve, wet AMD subjects to be
enrolled at 60 US sites
https://ir.outlooktherapeutics.com/static-files/2cfae876-3be2-46cb-aa75-aca673544481
The update to cliniclaltrials does not change the estimated dates, which indicates the planning is being kept:
* Study Start2024-01-24 [Actual]
* Primary Completion2024-09 [Estimated]
* Study Completion2024-10 [Estimated]
OTLK continues to execute on their plan.
Best of luck with your investments!
The 60 sites:
Arcadia, California, United States, 91006
Bakersfield, California, United States, 93309
Beverly Hills, California, United States, 90210
Huntington Beach, California, United States, 92647
Laguna Hills, California, United States, 92653
Long Beach, California, United States, 90807
Modesto, California, United States, 95356
Oakland, California, United States, 94611
Pasadena, California, United States, 91107
Poway, California, United States, 92064
Sacramento, California, United States, 95841
Colorado Springs, Colorado, United States, 80909
Lakewood, Colorado, United States, 80228
Waterford, Connecticut, United States, 06385
Coral Springs, Florida, United States, 33067
Fort Lauderdale, Florida, United States, 33308
Jacksonville, Florida, United States, 32216
Orlando, Florida, United States, 32806
Stuart, Florida, United States, 34994
Oak Forest, Illinois, United States, 60452
Oak Park, Illinois, United States, 03440
Lenexa, Kansas, United States, 66215
Lexington, Kentucky, United States, 40509
Hagerstown, Maryland, United States, 21740
Edina, Minnesota, United States, 55435
Saint Louis Park, Minnesota, United States, 55416
Jackson, Mississippi, United States, 39202
Teaneck, New Jersey, United States, 07666
Albuquerque, New Mexico, United States, 87109
Liverpool, New York, United States, 13088
Oceanside, New York, United States, 11572
Rochester, New York, United States, 14620
Westbury, New York, United States, 11590
Asheville, North Carolina, United States, 28803
Hickory, North Carolina, United States, 28602
Wake Forest, North Carolina, United States, 27587
Winston-Salem, North Carolina, United States, 27103
Edmond, Oklahoma, United States, 73013
Charleston, South Carolina, United States, 29414
Florence, South Carolina, United States, 29501
Ladson, South Carolina, United States, 29456
West Columbia, South Carolina, United States, 29169
Rapid City, South Dakota, United States, 57701
Germantown, Tennessee, United States, 38138
Abilene, Texas, United States, 79606
Arlington, Texas, United States, 76012
Austin, Texas, United States, 78705
Beaumont, Texas, United States, 77707
Bellaire, Texas, United States, 77401
Dallas, Texas, United States, 75231
Round Rock, Texas, United States, 78681
San Antonio, Texas, United States, 78240
San Antonio, Texas, United States, 78251
The Woodlands, Texas, United States, 77384
Willow Park, Texas, United States, 79606
Salt Lake City, Utah, United States, 84107
Fairfax, Virginia, United States, 22031
Lynchburg, Virginia, United States, 24502
Bellevue, Washington, United States, 98004
Silverdale, Washington, United States, 98383
H2R
2 months ago
1 more site, so 59 sites now
* Oceanside, New York, United States, 11572
See: https://clinicaltrials.gov/study/NCT06190093?term=norse%20eight&checkSpell=false&rank=1#contacts-and-locations
They had planned for 60, again, not sure they'll need all, but that's 1 to go if so.
Minor good non-news: Even though the update is dated 5/30 or 6/3 depending on how you read it, the estimate dates remain the same:
* Study Start: January 24, 2024
* Primary Completion: September 2024 [Anticipated]
* Study Completion: October 2024 [Anticipated]
The current list of recruiting sites:
Arcadia, California, United States, 91006
Bakersfield, California, United States, 93309
Beverly Hills, California, United States, 90210
Huntington Beach, California, United States, 92647
Laguna Hills, California, United States, 92653
Long Beach, California, United States, 90807
Modesto, California, United States, 95356
Pasadena, California, United States, 91107
Poway, California, United States, 92064
Sacramento, California, United States, 95841
Colorado Springs, Colorado, United States, 80909
Lakewood, Colorado, United States, 80228
Waterford, Connecticut, United States, 06385
Coral Springs, Florida, United States, 33067
Fort Lauderdale, Florida, United States, 33308
Jacksonville, Florida, United States, 32216
Orlando, Florida, United States, 32806
Stuart, Florida, United States, 34994
Oak Forest, Illinois, United States, 60452
Oak Park, Illinois, United States, 03440
Lenexa, Kansas, United States, 66215
Lexington, Kentucky, United States, 40509
Hagerstown, Maryland, United States, 21740
Edina, Minnesota, United States, 55435
Saint Louis Park, Minnesota, United States, 55416
Jackson, Mississippi, United States, 39202
Teaneck, New Jersey, United States, 07666
Albuquerque, New Mexico, United States, 87109
Liverpool, New York, United States, 13088
Oceanside, New York, United States, 11572
Rochester, New York, United States, 14620
Westbury, New York, United States, 11590
Asheville, North Carolina, United States, 28803
Hickory, North Carolina, United States, 28602
Wake Forest, North Carolina, United States, 27587
Winston-Salem, North Carolina, United States, 27103
Edmond, Oklahoma, United States, 73013
Charleston, South Carolina, United States, 29414
Florence, South Carolina, United States, 29501
Ladson, South Carolina, United States, 29456
West Columbia, South Carolina, United States, 29169
Rapid City, South Dakota, United States, 57701
Germantown, Tennessee, United States, 38138
Abilene, Texas, United States, 79606
Arlington, Texas, United States, 76012
Austin, Texas, United States, 78705
Beaumont, Texas, United States, 77707
Bellaire, Texas, United States, 77401
Dallas, Texas, United States, 75231
Round Rock, Texas, United States, 78681
San Antonio, Texas, United States, 78240
San Antonio, Texas, United States, 78251
The Woodlands, Texas, United States, 77384
Willow Park, Texas, United States, 79606
Salt Lake City, Utah, United States, 84107
Fairfax, Virginia, United States, 22031
Lynchburg, Virginia, United States, 24502
Bellevue, Washington, United States, 98004
Silverdale, Washington, United States, 98383
Best of luck with your investments!