GSK Announces Extension of FDA Review Period for Momelotinib

After all, GSK will not hear from the FDA this month about its marketing application for momelotinib as a therapy for anemia in myelofibrosis patients. The pharmaceutical company announced that the US Food and Drug Administration has extended the drug’s assessment period by three months, to September 16, “to allow time to review recently submitted data.” GSK has not provided any additional information regarding the new data, but it says it is “confident” in the application and “looks forward to working with the FDA as they finalise their review.”

Momelotinib, which was the lead asset in GSK’s $1.9 billion acquisition of Sierra Oncology last year, is expected to have blockbuster sales potential, filling an unmet need in myelofibrosis patients with anemia. Current myelofibrosis treatments, such as Novartis/Incyte’s JAK1/2 inhibitor Jakafi (ruxolitinib), can help ease symptoms and improve long-term survival, but they can also worsen anemia, a typical hallmark of blood malignancy. The most common reason for myelofibrosis patients to abandon treatment is anemia.

Momelotinib is a JAK1/2 inhibitor that also targets ACVR1, which can reduce levels of hepcidin, a protein that becomes high in myelofibrosis and contributes to anemia by blocking the iron release from macrophages and intestinal iron absorption. GSK is positioning momelotinib as a second-line therapy for myelofibrosis patients who develop anemia after Jakafi and other JAK drugs, such as Bristol Myers Squibb’s Inrebic (fedratinib) and CTI Biopharma’s Vonjo (pacritinib), and expects the drug to be a $1 billion-a-year blockbuster.

The drug is one of the highlights of GSK’s late-stage pipeline, which some analysts believe is a touch sparse as the company prepares for the loss of patent protection for HIV blockbuster dolutegravir, which is sold by its majority-owned subsidiary ViiV, and upcoming competition for the vaccination Shingrix. Along with momelotinib, the pharmaceutical company is banking on its recently approved respiratory syncytial virus (RSV) vaccine Arexvy and checkpoint inhibitor Jemperli (dostarlimab) to get it through that time.

FDA Approves Roche’s Columvi, the First and Only Bispecific Antibody for R/R DLBCL

The FDA approved Columvi® (glofitamab-gxbm) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma after two or more lines of systemic therapy. Based on the response rate and durability of response in phase I/II NP30179 research, this indication was granted accelerated approval. Continued clearance for this indication may be reliant on the clinical benefit being verified and described in a confirmatory investigation. Columvi will be accessible in the United States within the next few weeks. 

“People with diffuse large B-cell lymphoma who have gone through multiple lines of therapy have a poor prognosis and desperately need additional treatment options,” said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development at Roche. “We believe Columvi, as an off-the-shelf, fixed-duration treatment with durable response rates, could change the way this aggressive lymphoma is treated, reinforcing our commitment to bringing innovative treatment options to people with critical unmet needs.”

Columvi is the first and only CD20xCD3 T-cell engaging bispecific antibody for the treatment of R/R DLBCL that is given for a set period of time, as opposed to treat-to-progression approaches, which are given indefinitely until cancer progresses or the therapy becomes intolerable, whichever comes first. Columvi, which is intended to be completed in roughly 8.5 months, provides persons with R/R DLBCL with a target end date for their course of therapy as well as the potential of a treatment-free interval. Furthermore, Columvi is a chemotherapy-free therapeutic alternative that is ready for infusion.

TME Pharma Receives Investigational New Drug (IND) Approval for NOX-A12 From the US FDA

On June 15, 2023, TME Pharma N.V. (Euronext Growth Paris: ALTME) announced that the US FDA, after reviewing the comprehensive submission, has approved the company’s Investigational New Drug (IND) application to evaluate the company’s lead asset NOX-A12 in a Phase 2 study in pancreatic cancer (OPTIMUS) in the United States.

OPTIMUS is an open-label Phase 2 study designed to assess the safety and efficacy of NOX-A12 combined with anti-PD-1 pembrolizumab (Keytruda® from Merck) and two different chemotherapy regimens (nanoliposomal irinotecan/5-FU/Leucovorin or gemcitabine/nab-paclitaxel) in second-line pancreatic cancer. About 70 patients are anticipated to be enrolled in the trial at clinical locations in the US, France, and Spain, where the study has already received approval.

“The US Food and Drug Administration’s approval of our IND application is an important milestone for TME Pharma, as it represents the first review and approval of NOX-A12 – and more broadly the first review of our class of compounds – by the FDA. Now we will be able to test NOX-A12 in clinical trials in the US, and this is a very positive piece of news for the future development of NOX-A12. We have thus delivered on our promise to the market to bring the OPTIMUS IND application with the FDA to successful completion, allowing rapid resumption of the pancreatic cancer program once financing is available.”

Aram Mangasarian, CEO of TME Pharma

NOX-A12 is currently being developed in GLORIA, a Phase 1/2 study evaluating NOX-A12 in combination with radiotherapy and with or without bevacizumab in first-line glioblastoma brain cancer (glioblastoma) patients with tumors resistant to standard chemotherapy (with unmethylated MGMT promoter). TME Pharma is presently concentrating its resources and capabilities on the development of NOX-A12 in glioblastoma, as disclosed by TME Pharma in June 2022. Therefore, the OPTIMUS Phase 2 trial in second-line pancreatic cancer will be initiated once appropriate funding becomes available.

As per DelveInsight, in 2021, the total incident cases of pancreatic cancer in the 7MM countries were 175,000+ cases. Among the European countries, Germany had the highest number of incident cases of pancreatic cancer in 2021, i.e., 21,000+ cases, followed by France which had 14,000+ incident cases in 2021. On the other hand, Spain had the lowest number of incident cases of pancreatic cancer, i.e. 8,000+ cases in 2021. Japan had 43,000+ incident cases of pancreatic cancer in 2021. Apart from TME Pharma, several major pharma and biotech giants are actively working in the pancreatic cancer therapeutics market. 

Aldeyra Therapeutics Announces Key Updates from the Phase 3 INVIGORATE‑2 Trial of Reproxalap in Allergic Conjunctivitis

On Jun. 15, 2023, Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra) announced positive top-line results from the Phase 3 INVIGORATE-2 Clinical Trial of 0.25% reproxalap ophthalmic solution (reproxalap), an investigational new drug, in patients with allergic conjunctivitis. The clinical trial successfully achieved statistical significance for the primary endpoint and all secondary endpoints.

“Consistent with the results of the Phase 3 INVIGORATE Trial and in conjunction with a number of successful Phase 2 and Phase 3 clinical trials in dry eye disease, achievement of the primary endpoint and all secondary endpoints in INVIGORATE-2 supports the potential of reproxalap as a treatment for inflammatory diseases of the ocular surface. We believe that the rapid-onset activity of reproxalap evidenced in the INVIGORATE clinical trials may offer hope to allergic conjunctivitis patients who are today not adequately treated, and also to dry eye disease patients, up to 50% of whom suffer from ocular allergy.” 

Todd C. Brady, M.D., Ph.D., President and CEO of Aldeyra

Reproxalap, an investigational new drug candidate, is a first-in-class small-molecule modulator of RASP (reactive aldehyde species), which is elevated in ocular and systemic inflammatory disease. The mechanism of action of reproxalap has been supported by the demonstration of statistically significant and clinically relevant activity in multiple physiologically distinct late-phase clinical indications. Reproxalap has been studied in more than 2,400 patients across 21 clinical trials with no observed safety concerns; mild and transient instillation site irritation is the most commonly reported adverse event in clinical trials.

The randomized, double-masked, vehicle-controlled, two-way crossover design allergen chamber Phase 3 INVIGORATE‑2 Trial enrolled 131 allergic conjunctivitis patients. The primary efficacy endpoint was a change from baseline in patient-reported ocular itching score on a 0‑4 point scale over a majority of 11-time points from 110 to 210 minutes after allergen chamber entry. The key secondary endpoint was a change from baseline in ocular redness on a 0‑4 point scale over the duration of the allergen chamber (approximately 3.5 hours).

A New Drug Application (NDA) of reproxalap for the treatment of dry eye disease is under review at the U.S. Food and Drug Administration. The NDA Prescription Drug User Fee Act (PDUFA) date for reproxalap for the treatment of dry eye disease is November 23, 2023.

As per the estimate, allergic conjunctivitis is a common eye condition that affects more than 20% of the population in the US. As per DelveInsight, the allergic conjunctivitis therapeutics market is anticipated to evolve immensely in the coming years owing to the rising cases in the 7MM, a better understanding of the disease, and the development of novel therapies. Several therapies are under development and are expected to hit the market in the upcoming years. 

Avita Medical Obtains FDA Approval of RECELL for Treating Vitiligo

AVITA Medical announced that its application for premarket approval of the RECELL System, designed to treat vitiligo, has been approved by the U.S. Food and Drug Administration. The FDA has granted its first-ever approval for a therapeutic device, providing a one-time treatment option at the point of care. By utilizing the RECELL System, medical professionals can now prepare and administer patient-specific skin cells from pigmented areas to treat stable depigmented vitiligo lesions, ensuring a secure and efficient therapeutic approach.

According to Jim Corbett, the CEO of AVITA Medical, the approval of RECELL marks a pioneering advancement in repigmentation treatment by utilizing the delivery of healthy and natural skin cells. He describes this approval as a significant breakthrough for AVITA Medical, as it greatly expands the range of clinical applications for the RECELL system. This achievement underscores the company’s unwavering dedication to providing exceptional care for patients. Corbett expresses enthusiasm in offering a valuable one-time treatment option for individuals with stable vitiligo throughout the United States.

The approval of the premarket application for the RECELL System was based on the findings from AVITA Medical’s pivotal trial, which aimed to assess the safety and efficacy of the system in repigmenting stable vitiligo lesions. The study involved comparing the success rates of repigmentation achieved with the RECELL treatment on areas of skin resurfaced using ablative laser, in contrast to the standard care treatment (control) administered on another area.

The evaluation of repigmentation was conducted by an expert central review committee at the 6-month and 12-month marks after treatment. The CRC determined that 36% of the RECELL treatments (compared to 0% of the control treatments) resulted in repigmentation of at least 80% of the treated area at the 6-month assessment. This outcome demonstrated a superior outcome for the primary endpoint (p<0.025), with 100% sustained repigmentation at the 12-month evaluation.

Additionally, at the 6-month mark, physicians responsible for administering the treatment reported a success rate of 68% for the RECELL treatment among patients. Furthermore, 80% of the patients themselves self-reported the RECELL treatment as successful.

The RECELL System is a device that harvests cells from the patient’s own skin, known as autologous cell harvesting. These cells are then used to prepare and administer a regenerative cell suspension called Spray-On Skin Cells. The Spray-On Skin Cells consist of various living cells that promote the healing process and stimulate repigmentation within the wound area. It is crucial to preserve melanocytes, as they play a vital role in restoring natural pigmentation to the treated region.

The suspension of Spray-On Skin Cells is specifically designed for application to skin that has been resurfaced using an ablative laser. Additionally, a portion of the Spray-On Skin Cells suspension can also be applied to the donor site.

The premarket application (PMA) underwent an expedited review process under the FDA’s Breakthrough Device program. This program is designed to grant priority review to medical devices that offer enhanced treatment options for conditions or diseases that are life-threatening or result in irreversible debilitation.

FDA Approves Odevixibat for ALGS Patients 12 Months And Up

Ipsen has announced that the FDA has granted approval for odevixibat as a treatment for cholestatic pruritus in Alagille syndrome patients aged 12 months and older, as per a press release. Odevixibat is described by the company as a once-daily, localized inhibitor of ileal bile acid transport (IBATi) that primarily acts in the small intestine and has minimal systemic exposure. This approval marks the second indication for odevixibat in rare cholestatic liver diseases in the United States. Previously, in 2021, it was approved for patients with cholestatic pruritus caused by progressive familial intrahepatic cholestasis (PFIC). Ipsen has stated that odevixibat is immediately accessible through prescription for eligible Alagille syndrome patients.

During the 2022 American Association for the Study of Liver Diseases Congress, the results of the phase 3 ASSERT study (NCT04674761) were presented. In this study, odevixibat demonstrated favorable outcomes and successfully achieved the primary objective. The primary endpoint of the study was a “highly statistically significant improvement in pruritus,” as measured by the PRUCISION Observer-Reported Outcome scratching score on a 0-4 point scale, at the 6-month mark (weeks 21 to 24), in comparison to the placebo group (P = 0.002).

The ASSERT study followed a double-blind, placebo-controlled, and randomized design. It assessed the safety and effectiveness of a daily dose of 120 µg/kg of odevixibat for a duration of 24 weeks. The study included patients from 32 locations across North America, Europe, the Middle East, and the Asia Pacific region, as mentioned by Ipsen.
Around 95% of individuals diagnosed with Alagille syndrome (ALGS), an inherited genetic disorder impacting various organs such as the liver, heart, skeleton, eyes, and kidneys, experience chronic cholestasis. Moreover, up to 88% of ALGS patients also suffer from severe and difficult-to-treat pruritus. In the United States, an estimated 1,300 patients could potentially qualify for treatment with ileal bile acid transport inhibitors (IBATi).