The approval of Lynparza was based on the findings of a late-stage study in which the drug demonstrated a statistically significant and clinically meaningful improvement in invasive disease-free survival, lowering the risk of invasive breast cancer recurrences, second cancers, or death by 42% compared to placebo.
Lynparza belongs to a drugs class known as PARP inhibitors, which prevent chemotherapy-damaged cancer cells from repairing themselves. With approvals for ovarian, prostate, and pancreatic cancers, it is a valuable asset for AstraZeneca. Lynparza generated USD 2.35 billion in sales for AstraZeneca last year, a 30% increase over 2020 at constant exchange rates. There are no company-sponsored Phase 3 trials in adjuvant breast cancer for other marketed PARP inhibitors, including GlaxoSmithKline’s Zejula, Clovis Oncology’s Rubraca, and Pfizer’s Talzenna. Merck will pay AstraZeneca a regulatory milestone payment of USD 175 million following the approval of Lynparza in the United States.
Venatorx Plans New Antibiotic Filing Following The Phase 3 Readout
Venatorx Pharma has taken another step toward what has unfortunately become a rare event in the pharmaceutical industry: the submission of a new antibiotic designed to address the growing problem of antimicrobial resistance.
Venatorx has announced that armed with positive Phase 3 results, and it will apply to the FDA for approval of its cefepime-taniborbactam combination for Complicated Urinary Tract Infections (cUTI), including Severe Kidney Infections, later this year.
The new drug combines cefepime, a well-known beta-lactam antibiotic, with a new beta-lactamase inhibitor designed to overcome a key resistance mechanism that pathogens use to protect themselves from antimicrobials.
Cefepime is a broad-spectrum antibiotic that was first introduced in the 1990s but has become increasingly ineffective against key resistant pathogens and was removed from the World Health Organization list of essential medicines in 2019.
In the 661-patient CERTAIN-1 trial, cefepime-taniborbactam was at least as effective as the comparator beta-lactam meropenem in clearing cUTIs, achieving combined clinical and microbiologic responses in 70% of patients versus 58% of those treated with the comparator drug. The Global Antibiotic Research and Development Partnership (GARDP), a Swiss non-profit founded in 2016 to combat antimicrobial resistance, has supported the development of the new combination. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam in certain low- and lower-middle-income countries and in public markets in India and South Africa, once it is approved for clinical use.
Bayer Submits Application for Additional Prostate Cancer Indications for Nubeqa
Bayer today declared the submission to the Ministry of Health, Labor and Welfare in Japan for an additional indication for the darolutamide (oral androgen receptor inhibitor). The application seeks marketing authorization for darolutamide in combination with docetaxel and androgen deprivation therapy for the treatment of patients suffering with prostate cancer with distant metastasis. Darolutamide is already marketed under the brand name Nubeqa™ for the treatment of patients with non-metastatic castration-resistant prostate cancer who are at high risk of developing metastatic disease.
The submission is based on the positive results from the pivotal Phase III ARASENS trial recently held at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and published in The New England Journal of Medicine. The results showed a statistically compelling improvement and development in overall survival for darolutamide + ADT & docetaxel compared to ADT + docetaxel in men with mHSPC.
“Annually, Prostate cancer is the most common new cancer diagnosis in Japanese men. Despite treatment breakthroughs, for a large proportion of patients living with metastatic hormone-sensitive prostate cancer, their disease will progress within 2 to 3 years. This highlights the unmet medical need for new and differentiated therapy options earlier in the patient’s treatment journey,” said Christine Roth.
Darolutamide is already approved under the brand name Nubeqa™ in more than 60 markets globally including the United States, the European Union, Japan & China, for the treatment of patients suffering with non-metastatic castration-resistant prostate cancer. The product is in joint collaboration by Bayer and Orion Corporation.
Additional filings for the indication of metastatic hormone-sensitive prostate cancer have been made in the United States and the European Union, and filings in other regions are underway. The compound is also being considered in further studies across different stages of prostate cancer.
NICE Rejects Keytruda Plus Chemotherapy for Triple-Negative Breast Cancer
The evidence demonstrated that pembrolizumab in combination with chemotherapy is more effective than paclitaxel/nab-paclitaxel, considering the long-term benefit is uncertain. Additionally, there was no trial data directly comparing pembrolizumab plus chemotherapy with atezolizumab plus chemotherapy, which is another targeted treatment option which NICE suggests.
The cost-effectiveness estimates are higher than the National Institute for Health and Care Excellence normally considers an acceptable use of NHS resources.
The committee would look out for more information from the organization about the analysis of comparison between pembrolizumab plus chemotherapy with atezolizumab plus chemotherapy.
“NICE suggests atezolizumab with chemotherapy, the only other targeted therapy for triple negative breast cancer, and another treatment is in our pipeline to be considered. There are people who are not eligible for atezolizumab combination who could be eligible for pembrolizumab with chemotherapy.
Given by injection every 3 weeks, pembrolizumab is a type of immunotherapy that individually targets triple negative breast cancer. It blocks the activity of a protein, PD-L1 which is produced in larger amounts on cancerous cells. By blocking the protein it helps the person’s own immune cells to attack the cancer.
Pembrolizumab is licensed for use with chemotherapy in adults with TNBC who have not had chemotherapy for metastatic disease and where surgery to remove the tumor is impossible.
Approximately 600 people in England with advanced triple negative breast cancer would have been eligible for treatment with the pembrolizumab combination.
Novartis’s Sandoz Acquires Coalesce Product Development Ltd.
In the latest commercial update from the pharmaceutical market, Sandoz, a Novartis division, has announced the acquisition of the UK-based medical and drug delivery device development company, Coalesce Product Development Limited. Sandoz is a global leader in the generic pharmaceuticals and biosimilars market with a strong presence in the respiratory medicines market and ‘complex’ generics.
Sandoz has an existing portfolio of six commercial products and nearly twice as many more in the pipeline. The acquisition of Coalesce will support and reinforce the existing capabilities of Sandoz in respiratory and complex generics. It will further assist Sandoz in improving the patient’s access to high-quality therapies. Moreover, Sandoz is looking forward to growing its portfolio in complex injectables.
Globally, respiratory diseases are the leading cause of death and disability. Chronic obstructive pulmonary disease (COPD), asthma, occupational lung diseases and pulmonary hypertension are some of the leading respiratory diseases causing huge financial and social strain on the affected person. Among them, Asthma is a major non-communicable disease affecting nearly 262 million people. Also, Chronic obstructive pulmonary disease (COPD) is another major disease that had led to nearly 3.23 million deaths in 2019. The ongoing clinical and commercial developments in the domain are expected to overcome the unmet medical needs in the coming years.
FDA Delays Decision on Incyte’s Drug Opxelura by 3 Months
Incyte Corporation has announced the US FDA has delayed the review period for the supplemental New Drug Application (sNDA) for ruxolitinib cream (Opzelura™) for vitiligo treatment. The Prescription Drug User Fee Act (PDUFA) action date has been extended by three months till July 2022.
Ruxolitinib cream (Opzelura) is a novel cream formulation of selective JAK1/JAK2 inhibitor ruxolitinib. Additionally, it is the first and only topical JAK inhibitor approved for the topical short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in the US.
Ruxolitinib is currently under the Phase 3 TRuE-V clinical trial program (TRuE-V1 and TRuE-V2) in more than 600 adolescent and adult patients (age 12 and older) with non-segmental vitiligo. The extended PDUFA action date will allow time for FDA to review additional data from the ongoing Phase 3 studies.
Earlier in October 2021, the Incyte announce the validation of the European Marketing Authorization Application (MAA) for ruxolitinib cream as a potential treatment for non-segmental vitiligo with facial involvement in adolescents and adults (age >12 years). Similarly, in December 2021, Incyte confirmed the acceptance and priority review of the supplemental New Drug Application (sNDA) for ruxolitinib cream as a potential treatment for vitiligo.
Vitiligo is a depigmenting skin disorder that can affect people of all ages and affects both sexes equally. It is more common in people with autoimmune diseases, and it might run in families. As per the DelveInsight, Vitiligo has an estimated prevalence of 0.5–2% in both adults and children worldwide. The prevalence of Vitiligo based on Comorbidities ranges from 22%-9%. As of now, there is no cure for vitiligo and most of the therapies prescribed are “off label” that aims to create a uniform skin tone by either restoring colour (repigmentation) or eliminating the remaining colour (depigmentation).
AbbVie’s Qulipta Becomes First Oral Drug in CGRP Inhibitor Class for Migraine Prevention
AbbVie’s Qulipta has become first-in-league, an oral drug of the CGRP inhibitor class which was observed to have shown efficacy towards prevention of Chronic Migraine. The results were taken from a pivotal trial which concluded in setting up a new category of treatment previously dominated by injectable therapies. The clinical study of Qulipta is now in a Phase III PROGRESS trial, which is administered every day (either in a once-daily or twice-daily dose).
Qulipta received an FDA approval last September for Episodic Migraine preventive treatment. This event took place just a few months later when the drug’s main rival in the oral category of CGRP inhibitor – Biohaven’s Nurtec ODT (rimegepant), got a green flag for migraine. Bohaven did try to file its drug for both episodic and Chronic Migraine prevention, but the drug regulator decided to only give a nod for the prior category as the drug was found to be not strong enough for Chronic Migraine prevention.
Whereas on the other hand, Abbvie said that the filing of PROGRESS data with drug regulators shall be done very soon in order to extend the label for Qulipta for inclusion of Chronic Migraine affected people giving it a slight edge over its rival drug. Chronic Migraine is defined as a person experiencing at least 15 migraine days per month for a duration of least 3 months. And Episodic Migraine includes people who experience 0 to 14 migraine days per month.
The PROGRESS trial includes 778 migraine patients who have been experiencing headaches on 15 or more days per month, for a duration of at least 3 months, and the drug was administered as 30 mg twice or 60 mg once per day dose schedule. As Chronic Migraine remains highly under-treated as of now, this drug can prove to be a blockbuster among people who either don’t respond to the injectable drugs or have a needle phobia.
FDA Rejects AstraZeneca’s Fasenra Bid For Nasal Polyps Indication
AstraZeneca received a red flag for its IL-5 inhibitor Fasenra as a Chronic Rhinosinusitis treatment for people experiencing Nasal Polyps. FDA rejected its marketing appeal and has asked for further clinical trial data. AZ hopes to join Fasenra (benralizumab) in the league of rival drugs from Sanofi/Regeneron and GlaxoSmithKline as Chronic Rhinosinusitis with Nasal Polyps treatment (CRSwNP), as few of the approved therapies which have shown to be effective in reducing symptoms. Sanofi/Regeneron’s IL-4 and IL-13 inhibitor Dupixent (dupilumab) received FDA approval in 2019, and was then joined by GSK’s IL-5 inhibitor Nucala (mepolizumab) last year in the US market.
AstraZeneca’s bid to market Fasenra was based on the Phase III OSTRO trial results which indicated a statistically significant improvement in the endoscopic total nasal polyp score and nasal blockage score compared to placebo, in patients experiencing severe Chronic Rhinosinusitis with Nasal Polyps and who were even symptomatic despite standard care.
Fasenra has already received an FDA approval for Severe Eosinophilic Asthma as an add-on maintenance treatment. This drug was a megahit and generated a revenue of USD 1.3 billion in sales last year. In addition to that, the drug is currently being tested for few other indications as well which include Hypereosinophilic Syndrome (HES) and Eosinophilic Oesophagitis, with Phase 3 results anticipated later this year.
