FDA Approves Incyte’s Opzelura as First Vitiligo Therapy

The US Food and Drug Administration has approved Incyte’s Opzelura cream 1.5% for the topical treatment of non-segmental vitiligo in adult and paediatric patients 12 years of age and older.

With this approval, Opzelura is the first and only FDA-approved treatment for repigmentation in patients with vitiligo. It is also the superior topical formulation of a Janus kinase inhibitor approved in the US.

Vitiligo is a chronic autoimmune disease presenting a skin depigmentation caused by the loss of melanocytes, which are pigment-producing cells. Around 1.5 million people are diagnosed with vitiligo in the US. At the same time, the total prevalence of the condition is estimated to be around 2-3 million, with the majority of patients, around 85% who are suffering from non-segmental vitiligo.

An over-activity of the JAK signalling pathway is thought to drive further inflammation in the progression of vitiligo.

The FDA based its decision on conclusions taken from the pivotal phase 3 TRuE-V clinical trial programme, which evaluated the safety and efficacy of Opzelura versus non-medicated cream in more than 600 people with nonsegmental vitiligo, specifically in those aged 12 years and older.

The results showed that treatment with Opzelura significantly improved Vitiligo Area Severity Index scores, representing improvements in facial and complete body repigmentation at week 24 as compared to non-medicated cream and in an open-label extension at week 52.

The FDA approved Opzelura in September 2021 for the topical short-term and non-continuous chronic treatment of mild-to-moderate atopic dermatitis in non-immuno-compromised patients of age 12 years and older whose disease is not controlled with topical prescription treatments, or when those treatments are not suitable.

FDA Grants Fast Track and Rare Pediatric Disease Designations to WU-CART-007 in R/R T-ALL and LBL

The FDA has granted fast-track and rare pediatric disease designations to the CAR T-cell therapy WU-CART-007 for treating patients with relapsed/refractory T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma. WU-CART-007 is an allogeneic and fratricide-resistant CD7-targeted CAR T-cell therapy. The product is made to overcome the technological challenges of harnessing CAR-T cells to treat CD7-positive haematological malignancies. WU-CART-007 is under evaluation in a phase I/II trial in patients with relapsed/refractory T-ALL or LBL.

Preclinical studies demonstrates that WU-CART-007 displayed high affinity and specificity for human CD7. Investigators observed potent cytotoxicity against CD7-expressing cells, including CCRF-CEM T-cell acute lymphoblastic leukaemia cells, primary T and NK cells in vitro, but not seen in CD7 cells, for instance, hepatocytes, astrocytes, cardiomyocytes, myeloid cells, B-cells, endothelial cells, and epithelial cells. Moreover, they did not observe cytotoxicity against hematopoietic progenitor cells in human bone marrow or cord blood.

The global, open-label, first-in-human trial enrols patients with evidence of relapsed or refractory T-cell acute lymphoblastic leukaemia or T-LBL, defined by WHO classification with bone marrow blasts of at least 5% or evidence of extramedullary disease at screening. Other critical inclusion criteria for the study include adequate renal, respiratory, hepatic, and cardiovascular function, also a life expectancy of more than 12 weeks.

The lower age limit of the trial is 12 years, and patients between 12-17 years old will be eligible to enrol at dose level 3 of the dose-escalation portion of the problem after a review of safety, efficiency and cellular pharmacokinetics and discussion with regulatory agencies.

Critical exclusion criteria include prior treatment with any anti-CD7 therapy; initial treatment with anti-T cell monoclonal antibodies other than daratumumab; failure to recover from a previous treatment; active hepatitis B & hepatitis C, any other uncontrolled infection, or untreated HIV positive; and any severe active disease at the time of treatment, or another underlying severe morbidities that could influence study treatment.

After enrollment, patients will undergo lymphodepletion with a daily dose of 500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine 30 mg/m2 on days -5 to -3. On the first day, the patients will receive an intravenous infusion of WU-CART-007.

The trial’s primary endpoints include :

  • Incidence of adverse effects.
  • Establishing the maximum tolerated dose.
  • Overall response rate.
  • Duration of response.
  • Progression-free survival. 

Secondary endpoints consist of overall survival and hematopoietic stem cell transplant rate.

VistaGen Therapeutics’ PH94B Fails in the First of Two Phase III trials in Social Anxiety Disorder 

Vistagen Therapeutics Inc’s investigational drug, PH94B, was formulated for anxiety treatment, depression, and other central nervous systems (CNS) disorders. The previous results indicated favourable safety and tolerability profile among study participants, but the topline results fell short of the next hurdle. PH94B is made to regulate the olfactory-amygdala neural circuits of fear and anxiety, but the drug did not achieve its primary endpoint of change from baseline using the Subjective Units of Distress Scale (SUDS) when compared to placebo. The results were established from a PALISADE-1 Phase 3 clinical trial for social anxiety disorder in adults. PH94B is supposedly a tasteless, odourless, rapid-onset pherine nasal spray planned to regulate the olfactory-amygdala neural circuits of fear and anxiety.

VistaGen chief executive officer Shawn Singh said: “While the results of PALISADE-1 are not consistent with prior positive results from Phase 2 trials of PH94B in social anxiety disorder, we remain committed to transforming the treatment landscape for those living with anxiety, depression, and other central nervous system disorders. “As part of this commitment, our team will continue to pursue PH94B’s potential as a new treatment option for multiple anxiety disorders — including for both acute treatment for social anxiety disorder in our ongoing PALISADE-2 Phase 3 trial and for continued use in our ongoing Phase 2 trial in adjustment disorder with anxiety.

PALISADE-1 clinical trial is a randomised, multi-centre, double-blind, parallel design, placebo-controlled, Phase 3 clinical study in adults experiencing social anxiety disorder (SAD). The clinical trial was designed to evaluate the efficacy, safety, and tolerability of the acute administration of PH94B to relieve symptoms of anxiety in adult patients with SAD.

Additionally, VistaGen has two other drug candidates in its central nervous system pipeline, PH10 and AV-101, as potential treatments for anxiety, depression and other central nervous system disorders.

Bid to Expand Keytruda Use in Head and Neck Cancer Therapy Fails

The very recent immunotherapies have provided cancer treatment for many types. The transformation in cancer treatment is very hopeful for some cases, but they do sometimes tend to fail or have an impact – as Merck & Co has experienced in a study of Keytruda in head and neck cancer. The PD-1 inhibitor failed in Phase 3 KEYNOTE-412 trial in 780 newly-diagnosed patients with head and neck squamous cell carcinoma (HNSCC), a notoriously hard-to-treat form of cancer. The clinical trial study compared Keytruda (pembrolizumab) given with cisplatin and radiotherapy – followed by maintenance therapy with Keytruda for around a year – to placebo plus cisplatin and radiotherapy and placebo during the maintenance phase.

The results indicative for the primary endpoint of the study was even-free survival, but there was no statistically significant difference between the groups on this measure, even though patients on the PD-1 therapy did slightly better. Keytruda- a blockbuster drug has been approved since 2016 as a second-line option after chemotherapy for patients with more advanced disease, i.e. recurrent or relapsed Head and neck squamous cell carcinomas that have metastasised to other parts of the body.

The study results of KEYNOTE-412 rushes Merck’s hopes of extending Keytruda’s indications in HNSCC to non-metastatic disease in an all-comer population, regardless of PD-L1 status. Currently, the only another immunotherapy approved to treat HNSCC is Bristol-Myers Squibb’s Opdivo (nivolumab), which can be used as a second-line option after chemotherapy.

Merck says it is committed to “investigating Keytruda-based regimens for this debilitating type of cancer in earlier stages of disease.”

EMA Approves Bavarian Nordic’s Smallpox Vaccine Imvanex

The European Medicines Agency has expanded the permitted indications for Bavarian Nordic’s smallpox vaccine Imvanex for monkeypox, which has now infected tens of thousands of individuals in dozens of countries around the world. Imvanex has been approved in the EU since 2013 for smallpox, a virus related to monkeypox, and should not be approved to protect adults from monkeypox disease, according to the CHMP. Two years after calling COVID-19 a “public health emergency of international concern,” the World Health Organization (WHO) has officially declared monkeypox a “public health emergency of international concern.”

Since the virus’s first appearance two months ago, there have been over 16,000 cases reported from 75 countries, with more than two-thirds detected in Europe, a size of outbreak never before seen with the virus. After analyzing data from many animal studies that indicated protection against the monkeypox virus in nonhuman primates inoculated with Imvanex, the EMA’s human medicines committee, the CHMP, recommended approval of the monkeypox vaccine on last Friday. 

In June, the company announced that it had received orders for 1.5 million doses of the injection from an unidentified European country, with delivery set to begin in the fourth quarter. It had previously secured supply deals with the US and Canada – where the vaccine is known as Jynneos – for around 7 million doses, with approximately 1 million doses anticipated to be delivered this year.

CAMP4 Raises USD 100 Million to Take Lead RNA Drugs into Clinic

CAMP4 Therapeutics is prepared to begin the first clinical study of a drug targeting regulatory RNA (regRNA) molecules, which can be used to fine-tune gene expression, with a USD 100 million second-round financing. CAMP4 believes that antisense oligonucleotide (ASO) treatments targeting these regRNA regions have the ability to increase protein production from any disease-associated gene, thereby addressing hereditary diseases “at their core.” The newest fundraising round, led by Enavate Sciences and including new investors Gaingels, an unidentified managed care organization, and existing backers, will give the company the funds it needs to push two of its ‘RNA actuator’ candidates into clinical testing. The first will be a chemical meant to treat Dravet syndrome, a rare form of persistent epilepsy that can cause dozens of seizures each month and for which there are few effective medicines – and none that address the fundamental cause of the disease.

Dravet syndrome is caused in around 80% of cases by abnormalities in a gene coding for a sodium channel – SCN1A – which is necessary for the proper functioning of neurons in the brain. CAMP4’s medication intends to upregulate SCN1A function to eliminate seizures, and human trials are set to begin in mid-2023.

AstraZeneca and Merck’s Lynparza Fails Colorectal Cancer Trial

In one of the latest failures in the clinical drug development segment, Merck has announced that it has stopped the Phase III LYNK-003 trial evaluating PARP inhibitor Lynparza. Lynparza is being studied in patients with unresectable or metastatic colorectal cancer who have not progressed following first-line induction. Lynparza is an immuno-oncology drug and co-developed & co-commercialized by Merck in association with oncology pharma giant AstraZeneca. The decision was based on the recommendation of an independent Data Monitoring Committee following the review of data at an interim analysis. 

In the Phase III LYNK-003 study, Lynparza is being evaluated in 309 patients with unresectable or metastatic colorectal cancer. No new safety signals were observed with Lynparza in patients. Merck has further stated that it will convey the decision to stop a study of Lynparza to the patients and study investigators. 

Merck and AstraZeneca are also assessing the potential of Lynparza as both a monotherapy and in new combinations for other cancer types, including ovarian cancer, breast cancer and pancreatic cancer.

At the pre-specified interim analysis for progression-free survival, the efficacy of Lynparza as a monotherapy and in combination with bevacizumab relative to control met the criteria for futility. Both experimental arms will be discontinued. 

FDA Grants Orphan Drug Designation to DSP-0390 for Brain Cancer

In the latest development in the Brain Cancer therapeutics market, the Food and Drug Administration (FDA) has granted Orphan Drug Designation to Sumitomo Pharma Oncology’s DSP-0390 for Brain Cancer treatment.

DSP-0390 is an investigational emopamil-binding protein (EBP) inhibitor for treating brain cancer. DSP-0390 mediates de novo cholesterol synthesis for cell membrane structure and signalling, enabling aberrant growth of tumors. The therapy is being studied in a Phase 1 clinical trial in patients with recurrent, high-grade glioma, which is being conducted in the United States and Japan. DSP-0390 has shown cytotoxic activity against Glioblastoma, colorectal cancer, and triple-negative breast cancer in vitro. 

Earlier, SMP Oncology’s TP-3654 also received Orphan Drug Designations.  It is the second therapy that has received Orphan Drug Designations recently.  TP-3654 is a proprietary investigational oral inhibitor of PIM kinases for treating myelofibrosis. 

Brain cancer also referred to as brain tumors, leads to the abnormal growth of cells in the brain and is malignant. Further investigation and the development of the novel therapies like DSP-0390 are expected to improve the overall treatment scenario in the coming years.