FDA Approves Yescarta as a First CAR T-cell Therapy for Initial Treatment of R/R Large B-cell Lymphoma

Until now, existing CAR-T therapies have been reserved for patients with blood cancer who have tried multiple treatments. The FDA has approved Yescarta, a CD19-directed CAR-T therapy developed by Gilead Sciences’ Kite Pharma, for the treatment of patients with Large B-cell Lymphoma that is refractory to one prior therapy or that relapses within 12 months of first-line chemoimmunotherapy.

Yescarta’s approval has put it ahead of Bristol Myers Squibb’s rival drug Breyanzi, which is expecting an FDA decision for the same second-line lymphoma indication by June 24. The FDA approval was based on Phase 3 Zuma-7 trial. According to the study, Yescarta reduced the risk of disease progression, death, or the need for a new therapy by 60.2% when compared to the standard of care, which includes chemotherapy and stem cell transplant. At two years, 40.5% of Yescarta participants were still alive and had not required additional cancer treatment or experienced cancer progression, compared to 16.3% in the control arm.

Kite will almost certainly face second-line competition from Bristol Myers’ CAR-T therapy Breyanzi, which reduced the risk of event-free survival by 65.1% in its own Phase 3 trial. Kymriah, Novartis’ CD19-targeted CAR-T therapy, previously failed in second-line Large B-cell Lymphoma (LBCL). Kite already has a three-year market lead with Yescarta over Breyanzi. Kite has also made significant investments in manufacturing to ensure a consistent supply and a short turnaround time. During the pandemic, the company received approval for an Amsterdam site, and it expects a Maryland facility to receive clearance and begin commercial production by mid-year. In addition, the third facility in Oceanside, California, has recently started producing engineered viral vectors for cell therapy in collaboration with an outside contractor.

FDA approves Nobelpharma’s HYFTOR™ (sirolimus topical gel) 0.2%

Nobelpharma America has announced that the U.S. Food and Drug Administration (FDA) has approved HYFTOR™ (sirolimus topical gel) 0.2% as the first topical treatment therapy for facial angiofibroma associated with Tuberous Sclerosis Complex (TSC). The therapy is approved for use in adults and children aged 6 or older. Additionally, Nobelpharma has received Orphan Drug status for HYFTOR™ for this indication.

In the clinical trials, sirolimus was found to improve the size and redness of facial angiofibroma at 12 weeks. Sirolimus is not supposed to be used in patients with a history of hypersensitivity to topical medication or other gel components.

Tuberous Sclerosis Complex is a rare genetic condition affecting various parts of the body such as the skin, central nervous system, heart, kidney, lung, and other sites. As per DelveInsight, in the United States, nearly 50,000 people are affected with Tuberous Sclerosis Complex, and about 1 to 2 million individuals worldwide. The estimated Tuberous Sclerosis Complex prevalence is one in 6,000 newborns. Facial angiofibroma is observed in approximately 75%-80% of TSC patients and results in facial skin lesions. The approval of the HYFTOR™ (sirolimus topical gel) 0.2% is expected to significantly improve the health outcome for the affected individuals.

Biogen and Ionis’ Drug BIIB078 Fails in Phase 1 Trial for Amyotrophic Lateral Sclerosis

In one of the latest clinical updates, Biogen and Ionis Pharmaceuticals have announced the failure of their potential drug BIIB078 (IONIS-C9Rx) for Amyotrophic Lateral Sclerosis (ALS). BIIB078 is an investigational antisense oligonucleotide for the treatment of C9orf72-associated Amyotrophic Lateral Sclerosis

In the phase I clinical-stage, BIIB078 was evaluated in a randomized, placebo-controlled, dose-escalating trial to assess the efficacy of the therapy administered intrathecally to adults (n=106). The therapy was unable to meet any secondary efficacy endpoints and failed to show clinical benefit. Further, Biogen has announced to discontinue the clinical program.

Amyotrophic Lateral Sclerosis, commonly known as Lou Gehrig’s disease, is a group of rare neurological diseases that mainly involve the nerve cells (neurons). C9orf72-associated ALS is a complex genetic form of ALS. As per DelveInsight, the Amyotrophic Lateral Sclerosis prevalent population in the seven major markets was found to be 71,600+ in 2020 and is expected to grow during the forecast period.  Furthermore, the diagnosed prevalent cases of ALS in the United States were 18,800+ in 2020. As of now, there is no cure and proven treatment for ALS. However, pharma and biotech companies are vigorously exploring the ALS treatment landscape. Biogen is also actively working in the Amyotrophic Lateral Sclerosis Therapeutics Market with several investigational drugs in the ALS pipeline such as tofersen, BIIB105, and BIIB100.

Cerevance preps Pivotal Trials of Parkinson’s drug after Phase 2 Success.

Cerevance, a clinical-stage drug discovery and development company focused on central nervous system diseases, has announced the successful completion of its Phase II clinical trial of CVN424, the company’s first-in-class, once-a-day, an orally-delivered compound in development to treat Parkinson’s disease. Apart from safety objectives, the drug achieved a compelling, dose-dependent reduction of “OFF-time,” which refers to time periods of the day when Parkinson disease’ symptoms recur despite medication. 

CVN424 was evaluated in a double-blind, randomized, placebo-controlled multicenter Phase II study at two dose levels in Parkinson’s disease patients with motor fluctuations. Approximately 135 subjects with Parkinson’s disease were enrolled on a stable dosage of levodopa and other Parkinson’s therapies but with at least two hours or more per day of average OFF time. Following the baseline safety & efficacy assessments, subjects were randomized to receive once-daily doses of low-dose CVN424, high-dose CVN424, or a matching placebo for four weeks.

CVN424 showed a 1.3 hour improvement in OFF-time at the high dose as compared to placebo at four weeks. This was accompanied by a rise in ON-time without Troublesome Dyskinesia, without a meaningful worsening of ON-Time with Troublesome Dyskinesia. Efficacy enhanced at four weeks in comparison with two weeks, and daytime sleepiness as measured by the Epworth Sleepiness Scale was reduced compared to placebo, differentiating it from most Parkinson’s disease drugs used as adjuncts to levodopa. At the lower dose, CVN424 also showed a meaningful improvement in OFF-time and ON-time without Troublesome Dyskinesia compared to placebo. The most prevailing adverse effects were vomiting, nausea, and headache, occurring in two subjects each at the higher dose. All other adverse reactions appeared in one issue or less.

Cerevance intends to pursue additional Phase II/III clinical studies with CVN424 to build a clear pathway to regulatory approval of the drug for the adjunctive therapy. The company will assess the drug’s promise as a stand-alone treatment for recently diagnosed patients not yet treated with levodopa.

FDA Grants Priority Review to Sanofi and Regeneron’s Dupixent for Eosinophilic Esophagitis

The Food and Drug Administration has granted Breakthrough Therapy designation to Dupixent to treat patients 12 years and older suffering with Eosinophilic Esophagitis (EoE). The identification for this investigational use is based on positive results from Part A of a Phase III trial in patients with eosinophilic esophagitis.

There are currently no FDA-approved medicines for Eosinophilic Esophagitis, a chronic and progressive type II inflammatory disease that breaks the esophagus and prevents it from functioning correctly. Over time, excessive type II inflammation causes scarring and narrowing of the esophagus, making it difficult to swallow. If left untreated, eosinophilic esophagitis can affect a patient’s ability to eat and cause food to become stuck after being destroyed (food impaction), leading to a medical emergency.

In the United States, there are around 160,000 patients with Eosinophilic Esophagitis who are currently being treated with different unapproved therapies or diet modifications. Of these patients, around 50,000 have failed multiple treatments.

Sanofi along with Regeneron previously reported positive results from Part A of the pivotal Phase III trial assessing Dupixent in patients 12 years and older suffering with EoE. Part A of the double-blind, randomized, placebo-controlled trial of 81 patients met both of its co-primary endpoints and all critical secondary endpoints. Patients who are treated on a weekly basis with Dupixent 300 mg over a 24-week treatment period have experienced a reduction in symptoms, esophageal inflammation, and abnormal endoscopic findings in the esophagus.

Part A of the trial also showed safety results consistent with the known safety profile of Dupixent in its approved indications. The eosinophilic esophagitis trial is ongoing, with additional patients enrolling in Part B and patients continuing in a 28-week extended active treatment period (Part C) after completing either Part A or Part B.

Breakthrough Therapy designation is expected to accelerate the development & review of drugs in the U.S. that target life-threatening diseases. Drugs qualifying for this designation must show preliminary clinical results that the drug may substantially improve clinically significant endpoints over available therapies or placebo if there are no available therapies. In 2017, Dupixent was granted Orphan Drug designation for the possible treatment of Eosinophilic Esophagitis. This is given to investigational medicines intended to treat rare diseases that affect less than around 200,000 people in the United States. Dupixent’s potential use in eosinophilic esophagitis is currently under clinical development, and no regulatory authority has evaluated its safety and efficacy for this indication.

Covis Plans to File FDA Approval for Rubraca for Ovarian Cancer

Clovis intends to apply for FDA approval in the second quarter based on a positive readout. The anticipated FDA approval, will likely place Clovis’s Rubraca, a drug used for Epithelial Ovarian Cancer treatment alongside its competitor drugs from GlaxoSmithKline and AstraZeneca. Rubraca inhibited tumor development in all patients with BRCA mutations and HRD positive malignancies, as well as those with tumors that did not exhibit homologous recombination deficiencies (HRD). 

Nonetheless, given the new Rubraca data comes two years after FDA approvals for GSK’s Zejula and AstraZeneca, as well as Merck’s Lynparza in the first-line maintenance scenario, however, the Clovis drug’s market potential remains unknown. Moreover, Rubraca’s findings look competitive against Zejula, the only PARP inhibitor with a broad, all-comers nod in first-line maintenance. The drug “exceeded” the company’s expectations in the Phase 3 Athena-Mono trial, according to the company, as Rubraca monotherapy reduced the risk of progression or death from Ovarian Cancer by 48% compared to placebo in all patients independent of tumor biomarker status. 

Patients who took the drug witnessed no disease progression for 20.2 months, compared to 9.2 months for those who took a placebo. Rubraca lowered that risk by 35% in individuals without HRD in an exploratory subgroup study. Athena-Combo, the other phase of the Athena clinical programme, is investigating whether adding Bristol Myers Squibb’s PD-1 inhibitor Opdivo might further improve upon Rubraca monotherapy. The readout from that comparison has been pushed back into the first quarter of next year due to a slower-than-expected increase in disease progression or mortality occurrences. Clovis feels it has another opportunity to increase its market share in first-line maintenance.

Immunocore Eye Cancer Cell Therapy Scores European Approval

In one of the latest clinical development in TCR therapy domain, Immunocore Holdings plc received the European Commission (EC) approval for Kimmtrak (tebentafusp) for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM). Kimmtrak is a novel bispecific protein that combines a soluble T cell receptor with an anti-CD3 immune-effector function. It is the first therapy to show a survival benefit in patients with unresectable or Metastatic Uveal Melanoma.

Uveal melanoma is a rare and aggressive kind of melanoma that affects the eye. Although it is the most common primary intraocular malignancy in adults, detection is rare, and up to 50% of persons with uveal melanoma develop metastatic disease. However, the development of Kimmtrak signifies a paradigm change in the treatment of unresectable or metastatic uveal melanoma.

The EC approval comes after the Committee for Medicinal Products for Human Use (CHMP) issued a favorable opinion in February 2022. The CHMP recommendation for Kimmtrak is based on the findings of Immunocore’s Phase 3 IMCgp100-202 clinical study, which were published in the New England Journal of Medicine on September 23, 2021. The data for the biggest Phase 3 trial ever conducted in mUM, revealed that Kimmtrak provided an unparalleled median OS benefit as a first-line therapy. In the intent-to-treat population, the OS Hazard Ratio (HR) recommended Kimmtrak, HR=0.51, over the investigator’s treatment choice (82% pembrolizumab; 13% ipilimumab; 6% dacarbazine). Treatment-related side events were tolerable and consistent with the suggested mechanism of action in the randomized Phase 3 Kimmtrak (tebentafusp) study.

FDA Grants Fast Track Designation to Precigen’s Acute Myeloid Leukemia Treatment Candidate

The FDA has granted PRGN-3006 UltraCAR-T Fast track designation for the treatment of patients with relapsed or refractory Acute Myeloid Leukemia (R/R AML). The FDA previously designated the multigenic autologous chimeric antigen receptor (CAR)-T cell agent as an orphan drug for the treatment of R/R Acute Myeloid Leukemia. PRGN-3006 is currently being tested in a single-center, nonrandomized, investigator-initiated Phase 1/1b study. Patients with R/R Acute Myeloid Leukemia and those with high-risk Myelodysplastic Syndrome are both included in the study.

PRGN-3006 study is currently recruiting patients for a dose-escalation phase to determine the maximum-tolerated dose (MTD) of CAR T cells. The study’s coprimary endpoints are the number of patients who experience dose-limiting toxicities (DLTs) and the number of patients who experience treatment-related adverse events. The study’s secondary endpoints include disease progression in Acute Myeloid Leukemia patients, disease response in Myelodysplastic Syndrome patients, absolute lymphocyte count, and the number of PRGN-3006 T cells present in patients treated with the agent.

Patients must have R/R AML or high-risk MDS, an absolute lymphocyte count of 0.2 k/L, a Karnofsky performance score of 60%, and a life expectancy of at least 12 weeks to be eligible for the study. Patients must also have sufficient levels of serum bilirubin, alanine and aspartate aminotransferase, and ejection fraction. Those who have had an allogeneic stem cell transplant must be at least 3 months post-transplant before participating in the study.

The fast track designation will aid in the timely development of this program, and the company is looking forward to working even more closely with the FDA to potentially bring this new and highly differentiated overnight UltraCAR-T therapy to patients.