EU Recommends Approval for PTC Therapeutics’ Gene Therapy Upstaza

Upstaza, a gene therapy developed by PTC Therapeutics for patients with the genetic condition AADC deficiency, has been recommended for EU approval, putting another test of gene therapy’s commercial prospects in the union. Upstaza (eladocagene exuparvovec) will become the first disease-modifying medication for AADC deficiency, as well as the first gene therapy directly delivered into the brain. AADC deficiency is a rare fatal disorder that causes significant disability and suffering in children as early as the first months of life, with physical, mental, and behavioral symptoms including seizures.

The main question now is if PTC can construct an economically successful business for Upstaza in Europe, which has evaded other developers. UniQure’s Glybera for lipoprotein lipase insufficiency was licensed a decade ago; however, it was taken off the market a few years later due to low demand and concerns about its efficacy. Strimvelis, a drug developed by Orchard Therapeutics for the vanishingly rare “bubble boy” condition adenosine deaminase deficiency (ADA-SCID), was approved in 2016, but it is still only available through a single clinic in Italy and is used in too few patients to afford its price.

There are currently no approved therapies for the AADC deficiency treatment; thus the CHMP approved Upstaza “under exceptional circumstances” based on results from unblinded studies involving 28 children aged 18 months to eight years conducted primarily in Taiwan.

Sanofi and Regeneron’s Dupixent Become Wins First FDA Approval for Eosinophilic Esophagitis Treatment

With an FDA approval in Eosinophilic Esophagitis (EoE), Sanofi and Regeneron have added another string to their immunology blockbuster Dupixent’s bow, which might help the medication reach its €10 billion peak sales target. Dupixent (dupilumab) generated over €5 billion in sales last year from its current indications of Atopic Dermatitis, Eosinophilic Asthma, and Chronic Rhinosinusitis with Nasal Polyps, and EoE is one of a slew of new indications that Sanofi and Regeneron are counting on to boost sales even more. According to the company, the approval makes Dupixent the first and only EoE treatment in the United States, after the drug shown in a phase 3 trial that it could considerably relieve the indications and symptoms of the severe condition. According to the Dysphagia Symptom Questionnaire, a 300mg weekly dose of Dupixent reduced EoE symptoms by roughly two-thirds compared to a placebo in a phase 3 trial.

According to Sanofi, about 160,000 Eosinophilic Esophagitis patients in the United States are now being treated with corticosteroids and acid suppressants. More than a fifth of them will have tried various treatments and failed. The FDA granted approval two months ahead of schedule, highlighting the urgent need for new effective treatments for the disease. European regulators are also investigating Dupixent for EoE, and more files are expected before the end of the year in other nations. Sanofi and Regeneron are also developing Dupixent for other diseases characterized by type 2 inflammation, such as Atopic Dermatitis in children, some forms of Chronic Obstructive Pulmonary Disease (COPD), and Urticaria (hives).

Bayer Terminates CAR-T Collaboration with Atara Therapeutics

Atara Biotherapeutics has conveyed that Bayer informed intent to conclude the exclusive global licensing agreement for mesothelin-directed CAR T-cell therapies.

The companies entered the deal in December 2020 to develop CAR-T cell therapies to treat high mesothelin-expressing tumors such as non-small-cell lung cancer and malignant pleural mesothelioma (MPM). The partnership included financing and developing ATA3271 and ATA2271 for high mesothelin-expressing tumors like non-small cell lung cancer and malignant pleural mesothelioma (MPM). 

ATA3271 is an armored allogeneic T-cell immunotherapy, whereas ATA2271 is an autologous version. These candidates incorporate the inclusion of armoring of Atara in the form of a PD-1 DNR construct to bypass checkpoint inhibition and a 1XX costimulatory domain on the CAR to boost CAR T-cell expansion and functional persistence. 

ATA3271 uses the EBV T-cell platform of the company and is presently being analyzed in Investigational New Drug enabling clinical trials. The rights & licenses granted by Atara to Bayer under the partnership will be returned to the former upon deal termination in September this year. With this, Atara will gain exclusive rights to advance its programs’ clinical development and marketing globally in the future. The company will continue to back the Phase 1 clinical trial of ATA2271, carried out by Memorial Sloan Kettering Cancer Center. MSK has voluntarily discontinued the enrollment of new participants in the trial temporarily. 

Atara and MSK anticipate offering data updates from this trial in the second half of this year. Moreover, Atara will oversee ATA3271’s IND-enabling trials and process the development.

“We acknowledge Bayer’s decision to end our collaboration following Bayer’s strategic review and asset-level prioritization of its pipeline, including cell and gene therapy. “Based on the clinical & pre-clinical data generated upto date, we remain confident in the potential of ATA2271 and ATA3271 to address the needs of the patients suffering from solid tumors and are re-assessing our strategy on how best to generate value from the programs moving forward,” said Jakob Dupont, Head of Atara Biotherapeutics Global Research & Development.

In August last year, Bayer announced plans to acquire Vividion Therapeutics for up to $2bn to boost its drug discovery capabilities and expand into new modalities.

FDA Accepts Biohaven’s nasal spray drug Zavegepant for Migraine Treatment

The Food and Drug Administration (FDA) approved a New Drug Application for intranasal zavegepant (Biohaven, New Haven, CT) for acute treatment of migraine. Zavegepant is a nasal spray that provides pain relief as soon as 15 minutes. Pain relief is sustained for as long as 48 hours. The nonoral route also provides a new treatment option for individuals who have migraine attacks with nausea and vomiting. If approved, zavegepant will be the first intranasal drug in the class of gepants, which are antagonists of the calcitonin gene-related peptide (CGRP) receptor. 

“People suffering with migraine require an acute treatment that provides instant, long-lasting relief from the crippling symptoms of migraine. On approval, zavegepant would give a new treatment option for patients who need an ultra-rapid relief, in as early as around 15 minutes, and for those who experience nausea or vomiting and need a nonoral treatment option. We have generated robust data from phase 2 intranasal zavegepant pivotal trials that were submitted with our NDA and look forward to offering this new treatment option to people with migraine,” said Vlad Coric, MD, CEO & Chairman of Biohaven.

In 2 pivotal double-blind placebo-controlled studies (NCT04571060, NCT03872453), zavegepant had statistically significant superiority to placebo for freedom from pain and from most bothersome migraine-associated symptoms at 2 hours. The most bothersome symptoms were chosen from photophobia, phonophobia, and nausea. Higher rates of pain relief at 15 minutes, return to normal functioning at 30 minutes, and sustained pain freedom at 24 hours & 48 hours were also significantly higher with zavegepant vs. placebo.

“Many patients suffering with migraine need treatments other than pills for at least some of their migraine attacks. Swallowing a pill can make nausea worse, and medication cannot be injested if the patient vomits. Nasal sprays are a favoured option to tablets in many scenarios. In addition to this, many patients are dissatisfied with their current acute treatments and want faster relief. Zavegepant nasal spray will be an vital option for patients seeking non-oral therapies and faster relief. Though head-to-head studies are lacking, relative to triptan nasal sprays, zavegepant should provide favourable safety and tolerability, lack of cardiovascular contra-indications & precautions and a reduced risk of medication overuse,” said Richard B. Lipton, MD, Professor, and Vice-Chair of Neurology, Albert Einstein College of Medicine and director of the Montefiore Headache Center.

AbbVie Files FDA Approval for Parkinson’s disease Therapy ABBV-951

In the latest regulatory update, AbbVie has submitted a New Drug Application (NDA) to the USFDA for ABBV-951 (foscarbidopa/foslevodopa) for the treatment of motor fluctuations in patients with advanced Parkinson’s disease (PD). ABBV-951 consists of levodopa and carbidopa prodrugs that are delivered by a pump. AbbVie is expected to continue to pursue regulatory submissions for ABBV-951 across international markets throughout the year.

The submission is based on results from a Phase 3, head-to-head, randomized, and controlled clinical trial. The therapy has demonstrated statistically significant improvement in “On” time without troublesome dyskinesia compared to oral immediate-release carbidopa/levodopa (CD/LD). The therapy is designed to provide a first-of-its-kind, 24-hour, continuous subcutaneous delivery of CD/LD. 

As per DelveInsight, the total diagnosed prevalent population of Parkinson’s Disease is expected to rise to 3,284,000+ by 2030 in the 7MM (i.e. United States, EU5, and Japan). Globally, more than 10 million people worldwide are living with PD, and the majority of people start developing symptoms when they’re over 50, however, in some cases people start experiencing first symptoms when they’re under 40. Additionally, as per DelveInsight’s assessment males are more prominent for developing PD in comparison to females.

Innoviva to Acquire Entasis Therapeutics

Innoviva, Inc. and Entasis Therapeutics Holdings Inc. announced the companies have entered into a definitive merger agreement. As per the deal, the Innoviva will acquire all of the outstanding shares of Entasis not already owned by Innoviva at a price of $2.20 per share in cash. Innoviva has been a strategic investor in Entasis since 2020 and currently holds an equity stake of approx. 60% of the outstanding shares of Entasis common stock. Innoviva is a diversified holding company with a portfolio of royalties and other healthcare assets. The Company’s royalty portfolio contains respiratory assets. The acquisition is further expected to improve the market position of the company in the antibacterial product market.

The acquisition consideration values Entasis’ equity at $113 million on a fully diluted basis. The Board of Directors of both the companies have unanimously approved the acquisition deal. The transaction is anticipated to complete by the third quarter of 2022.

Established in 2015 as a spin-out from AstraZeneca, Entasis is a clinical-stage biopharmaceutical company focused on the discovery, development, and commercialization of targeted antibacterial products to treat serious bacterial diseases. Entasis’ pathogen-targeted design platform has produced a pipeline of product candidates which includes SUL-DUR, zoliflodacin, ETX0282CPDP, and ETX0462. 

FDA Grants Orphan Drug Designation to XMT-2056 for Gastric Cancer

The US Drug Regulatory granted an orphan drug designation to XMT-2056 for Gastric Cancer treatment developed by Mersana Therapeutics. The drug is an immunosynthen STING-agonist antibody-drug conjugate (ADC). The FDA grant came after a revelation that more than 100-fold increased potency was observed when compared to the free STING-agonist payload. In the mice model, XMT-2056 exhibited a robust anti-tumor immune activity, indicative of only minimal increases in systemic cytokine levels, and also the treatment showed significant benefit over the benchmark free STING-agonist payload.

XMT-2056 displayed activation of the STING pathway in both tumor-resident immune cells and tumor cells, which can then offer a potential advantage over other innate immune-activating pathways when studied in-vitro and in-vivo. As per an analysis by the American Cancer Society, Gastric cancer accumulates almost 1.5% of all new cancers diagnosed in the United States each year.

The drug was designed by the company to offer a complementary and differentiated therapeutic approach to emerging as well as existing solid tumor treatments. Mersana Therapeutics is looking forward to initiate a phase 1 trial of XMT-2056 in a range of different HER2 expressing tumors, such as non–small-cell lung cancers, breast cancer and gastric cancer, during the year 2022. Mersana has been previously involved in the process of developing and testing many other ADC’s such as, upifitamab rilsodotin (UpRi), a Dolaflexin ADC targeting NaPi2b, which is being studied in a clinical trial namely – UPLIFT, and in UPGRADE a phase 1/2 umbrella trial evaluating upifitamab rilsodotin in combination with other ovarian cancer therapies.

FDA Approves Azacitidine for Pediatric Patients with Newly Diagnosed Juvenile Myelomonocytic Leukemia

FDA gave a green signal to Azacitidine developed by Vidaza, Celgene Corp. for newly diagnosed Juvenile Myelomonocytic Leukemia treatment in pediatric patients. The FDA approval came on May 20, 2022, the approval came after the drug’s efficacy was evaluated in AZA-JMML-001, a multicenter, international, open-label study for evaluation of the pharmacodynamics, pharmacokinetics, safety, and activity of Azacitidine prior to hematopoietic stem cell transplantation (HSCT) in 18 pediatric patients with Juvenile Myelomonocytic Leukemia.

The primary efficacy result was clinical complete remission (cCR) or clinical partial remission (cPR) as per the International JMML response criteria at 3 months. These responses were to sustain at least for 4 weeks either in the 4-week period preceding or succeeding Cycle 3, Day 28. A combined total of 9 patients were present to confirm the clinical responses, out of which there were 3 cCR and 6 cPR. Adverse reactions that were observed mainly included pyrexia, upper respiratory tract infection, rash, and anemia.

The drug’s recommend dosage for JMML patients aged 1 month to less than 1 year or weighing less than 10 kg is 2.5 mg/kg. Whereas for patients ≥ age 1 and weighing ≥ 10 kg is 75 mg/m2. The application for this drug received a Priority Review and Breakthrough Designation. The review utilized the Assessment Aid, which is a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 1 month ahead of the FDA goal date.