AstraZeneca’s Danicopan Shows Positive Results in Phase III Trial

Danicopan, an oral Factor D inhibitor developed by AstraZeneca, was expected to fail a phase II trial in rare kidney disease in 2020, but a new readout could revive the drug. Danicopan (ALXN2040) has demonstrated efficacy as an adjunct treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH) who have extravascular hemolysis (EVH) – the breakdown of red blood cells in the spleen, bone marrow, or liver. The drug is being developed for use in PNH in combination with Alexion’s established C5 inhibitor therapies Soliris (eculizumab) and Ultomiris (ravulizumab), as well as for eye disease geographic atrophy.

It was discontinued for C3 glomerulopathy (C3G) in 2020 after failing a Phase II trial. ALXN2050, a follow-up Factor D inhibitor being developed by AstraZeneca/Alexion for C3G, as well as PNH and generalized myasthenia gravis, another disease treated with Ultomiris and Soliris.

People with PNH develop anemia as a result of blood cell destruction, as well as potentially fatal blood clots. Although some patients can live for decades with only minor symptoms, the median survival time after diagnosis is 10 years. Interim results from the ALPHA trial showed that adding danicopan to the C5 inhibitors resulted in a significant improvement in hemoglobin levels over a placebo after 12 weeks of treatment.

“These are the first positive phase III results for an oral factor D inhibitor and demonstrate the potential for danicopan add-on therapy to improve signs and symptoms and reduce the need for transfusions for the limited proportion of people living with PNH who experience clinically significant EVH,” said Alexion’s chief executive, Marc Dunoyer.

AZ stated that it plans to submit marketing applications for danicopan in PNH patients with EVH in the coming months. While this is most likely a small indication, the positive outcome bodes well for danicopan and ALXN-2050 in other applications with larger patient populations.

CHMP Recommends Sanofi/AstraZeneca Antibody for RSV Prevention

Sanofi and AstraZeneca are preparing to submit nirsevimab, a long-acting antibody for the protection of newborns and infants against respiratory syncytial virus (RSV) infections, to the European Union. The EMA’s human medicines committee, known as the CHMP, has recommended approval of a single dose of the antibody, known as Beyfortus, to prevent lower respiratory tract infections caused by RSV. Beyfortus, if approved, would be the first and only single-dose, passive immunization for a broad infant population, including those born healthy, at term or preterm, or with specific health conditions, according to a joint statement from AstraZeneca and Sanofi.

Synagis (palivizumab) by AstraZeneca is currently the only approved drug in Europe to provide passive RSV prophylaxis, but it must be administered monthly, whereas nirsevimab can provide protection throughout the RSV season. Sobi is the company that sells Synagis in the United States.

Despite losing patent protection, the former blockbuster is still selling well, with AstraZeneca earning USD 410 million from the drug last year. However, sales are expected to fall sharply once Beyfortus, and RSV vaccines hit the market. Pfizer is currently leading the race to bring an RSV vaccine to market for use by expectant mothers, which would transfer protection to newborns and infants, with phase III results expected next year.

“The positive CHMP opinion is one of the most significant public health achievements in RSV in decades and has the potential to alleviate the enormous physical and emotional burden that RSV can place on families and healthcare systems,” said Jean-François Toussaint, Sanofi’s head of vaccines R&D.

Sanofi invested USD 645 million in the nirsevimab program in 2017, paying for marketing rights to the antibody while AstraZeneca continued to develop and manufacture it. Sobi is also interested in the new drug as part of its 2019 Synagis agreement with AstraZeneca.

EMA Grants Orphan Drug Designation to CAN-2409 for Glioma

Candel Therapeutics has announced that the European Medicines Agency Committee for Orphan Medical Products issued a positive opinion on the company’s application for orphan drug designation for CAN-2409 treatment of Glioma. CAN-2409 is a genetically modified adenovirus and the company’s most advanced investigational therapy which is currently being evaluated in multiple phase II and phase III clinical trials for lung cancer, brain cancer, pancreatic cancer, and prostate cancer.

The orphan drug designation follows the U.S. FDA fast-track designation, which was granted in June 2021 for CAN-2409 combined with valacyclovir following standard of care treatment in newly diagnosed high-grade Glioma.

The European Commission grants orphan drug designation in the European Union based on a positive opinion issued by the EMA COMP. The EMA’s orphan drug designation is available to companies which are developing treatment and therapies for life-threatening or chronically debilitating conditions that affect no more than 5 in 10,000 persons in the European Union. Additionally, there must be sufficient clinical/non-clinical data to suggest the product candidate may produce clinically relevant results and grounds to indicate that it can provide a significant benefit over any currently authorized products. The designation can provide regulatory and financial incentives, including ten years of marketing exclusivity in the European Union after product approval, protocol assistance from the EMA at reduced price during the product development phase, and access to centralized marketing authorization.

FDA Starts Priority Review of Chiesi ‘s velmanase alfa

Chiesi Global Rare Diseases announced that the U.S. FDA has accepted the Biologics License Application and granted Priority Review designation for velmanase alfa, the company’s investigational enzyme replacement therapy for the proposed treatment of alpha-mannosidosis.

Alpha-mannosidosis is an ultra-rare genetic disorder that begins in childhood and progresses through adulthood. It is characterized by a deficiency of the enzyme alpha-mannosidase that results in the body’s cells being unable to break down certain groups of complex sugars properly. The sugar buildup can affect many body parts, organs and systems, including the central nervous system. Effects of the disease vary from person to person and progress over time. Symptoms may change as the patient ages, including distinctive facial features, recurrent ear and chest infections, hearing loss, muscle weakness, skeletal and joint abnormalities, and visual or cognitive abnormalities. Globally, the alpha-mannosidosis prevalence is approximately 1-9/1,000,000.

Velmanase alfa is a recombinant form of human alpha-mannosidase planned to offer natural alpha-mannosidase which is an enzyme that assists with the degradation of mannose–rich oligosaccharides to prevent their accumulation in various tissues in the body. In 2018, Chiesi Group received marketing authorization from the European Commission for Lamzede to treat non-neurological manifestations in patients suffering with mild to moderate alpha‑mannosidosis.

Akero’s NASH Drug Hits Targets in Phase IIb Trial

Akero Therapeutics has released topline data from Phase 2b HARMONY study, evaluating the efficacy and safety of its lead product candidate, efruxifermin (EFX), in patients with pre-cirrhotic nonalcoholic steatohepatitis (NASH), fibrosis stage 2 or 3 (F2-F3). EFX is designed to reverse fibrosis, reduce liver fat and inflammation, increase insulin sensitivity, and improve lipoproteins. 

Efruxifermin (EFX) is currently being evaluated in the ongoing Phase 2b HARMONY study. Akero’s HARMONY study is a multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial in biopsy-confirmed adult patients with pre-cirrhotic NASH, fibrosis stage 2 or 3. As per the statement issued by Akero Therapeutics, the study met its primary endpoint for both the 50mg and 28mg EFX dose groups, with 41% and 39% of EFX-treated patients, respectively, experiencing at least a one-stage improvement in liver fibrosis with no worsening of NASH by week 24, compared with 20% for the placebo arm. The study also met a key secondary endpoint and achieved NASH resolution without worsening fibrosis.

As per the American Liver Foundation, NAFLD is the most common chronic liver condition in the United States, and 25 percent of adults in the US have NAFLD; out of those, about 20% have NASH (5% of adults in the US). Currently, there is no standard treatment for patients with NASH. Majorly, NASH is managed with lifestyle changes that are shown to affect its progression. The lifestyle modification includes losing weight, maintaining a healthy diet, or addressing underlying conditions such as hypothyroidism and diabetes. It is observed that if the patient with NASH also has cirrhosis, the treatment may include medications and possibly surgery. People with NASH who develop liver cancer or liver failure may require a transplant. Akero’s NASH Drug efruxifermin (EFX) raises hope for a better option for the patients affected by NASH.

FDA Grants Orphan Drug Status to SY-5609 for Pancreatic Cancer

Syros Pharmaceuticals has announced that the US FDA has granted orphan drug designation (ODD) to its potential pancreatic cancer therapy, SY-5609. SY-5609 is a highly selective and potent oral cyclin-dependent kinase 7 (CDK7) inhibitor. 

The therapy is currently being evaluated in the Phase 1 trial in combination with chemotherapy to treat patients with relapsed metastatic pancreatic cancer who have progressed following treatment with FOLFIRINOX. Patients were randomized to receive either SY-5609 in combination with gemcitabine or SY-5609 in combination with gemcitabine and nab-paclitaxel, at the approved doses of the combination agents. The study is intended to assess safety and tolerability, as well as efficacy measures such as disease control rate and progression-free survival in patients with pancreatic cancer.

Following the announcement from Syros Pharmaceuticals, David A. Roth, M.D., Chief Medical Officer of Syros, stated, “this orphan drug designation underscores the urgency of our efforts to develop SY-5609 for patients with pancreatic cancer, one of the most devastating and difficult to treat malignancies,”. Syros Pharmaceuticals is expected to present the safety and clinical activity data from the safety lead-in portion of the trial in the second half of 2022.

Bristol-Myers Squibb’s Opdivo Shows Promising Results in Phase III Melanoma Trial

Bristol-Myers Squibb indicated that the first analysis of the phase III trial of Opdivo (nivolumab) showed better results with an increased response rate. The toxicity profile was also analyzed to be less than the preexisting chemotherapy techniques for metastatic melanoma. The study can potentially bring new therapies to encourage and aid the human body in fighting against cancer cells. The results of the study showed that almost 32% of the patient’s tumor cells were shrunk among the 11% population of chemotherapy patients. The drug showed a longer t1/2, and the response persisted for almost six months and longer, as compared to chemotherapy response that lasts upto 3.6 months. 

“I was very nicely surprised,” said Jeffrey Weber of the Moffitt Cancer Center in Florida. “A 32% response rate with the majority staying in remission past six months is probably going to turn into a very impressive level of survival,” he stated. “I hope this is the death knell for chemotherapy in melanoma.” The drug Opdivo (nivolumab) is designed for PD-1and PD-L1, which act as a source by which tumor cells evade the body’s immune system. 

Pfizer to File for FDA Approval for Meningitis Vaccine After Positive Phase III Result

After a successful phase III trial, Pfizer is all set to file for FDA approval for the new MenABCWY vaccine. The drug was assessed for its safety, tolerability, and immunogenicity and showed positive results after finishing the trial. The phase III trial comprised around 10 candidates each in the 25 years age group. The vaccine is developed against invasive meningococcal disease: serogroups A, B, C, W, and Y. MenACWY and MenB vaccines are the current two preexisting vaccines in the market to protect against all five serogroups. The results of MenABCWY showed increased immunity responses in non-vaccinated groups, i.e., up to ≥4-fold higher than pre-existingvaccines for meningococcal disease.

“We are very pleased with these positive Phase III data, which are the first for a MenABCWY vaccine candidate,” said Annaliesa Anderson, Ph.D., Senior Vice President, and Chief Scientific Officer, Vaccine Research and Development, Pfizer. “A pentavalent vaccine can help simplify the complex meningococcal vaccination schedule in the U.S. and improve vaccine coverage. Our goal is to help ensure as many adolescents and young adults as possible are protected against this devastating disease.”

Meningococcal disease is a lesser common but chronic disease that can result in death within 24 hours. Those who successfully survive the disease are left with lifelong impairments. Amongst five serotypes, B-serotype is accountable for causing maximum deaths in adolescents and young adults in the U.S. and Europe.