Daria G. Husni

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On Aug. 10, 2023, drug creation company Absci Corporation (ABSI) announced that its collaborative effort with the California Institute of Technology (Caltech) has received a grant from the Bill & Melinda Gates foundation. Led by Dr. Pamela Bjorkman, the collaboration combines research capabilities and advanced technological expertise in structural biology, protein design, synthetic biology, and generative AI to discover affordable HIV vaccinations. The teams will work to develop a novel HIB therapy that “that first exposes and then binds to a highly conserved epitope binding site on HIV-1 to potentially both treat and protect against infection from all strains of the virus,” as described in a press release by Absci.

While Antiretroviral therapies have helped those with the HIV virus live longer and healthier lives, in more than forty years after the AIDS pandemic began no vaccine or cure exists to completely cure HIV. The cost and inaccessibility of these drugs, which must be taken for life, also mean that treatment is often out of reach from millions of people from low-income and marginalized communities. Absci and Caltech aim to focus on the affordability, scalability, and accessibility of HIV therapeutic vaccinations.

“We are thrilled to receive this grant from the Bill & Melinda Gates Foundation,” said Dr. Stephen Mayo,Bren Professor of Biology and Chemistry and Merkin Institute Professor at Caltech and project co-leader. “We’re committed to making transformative contributions to society through research and innovation, and we are excited to partner with Absci, who has developed a powerful de novo AI antibody platform that is helping to unlock new therapeutic possibilities. This collaboration with Absci allows us to combine our expertise and work towards a common goal of developing affordable HIV therapeutic vaccinations that can save lives and bring hope to millions.”

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A major grant from the Bill & Melinda Gates Foundation will bolster efforts to fight the global HIV/AIDS epidemic.

Absci and Caltech Collaborate to Accelerate Affordable HIV Therapeutic Vaccine

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On Aug. 11, 2023, Novartis announced the completion of its acquisition of Chinook Therapeutics, a US-based clinical-stage biopharmaceutical company focused on developing and producing precision medicines for kidney diseases. The transaction included a $3.2 billion upfront payment, with a total deal value of up to $3.5 billion. Stockholders in Chinook are expected to receive up to $44.00 per Chinook share through a contingent value right, which represents a potential added $300 million in aggregate contingent consideration.

In a company press release, Novartis identified two key late-stage assets in development at Chinook: atrasentan and zigakibart (BION-1301). Both assets are being developed to treat Immunoglobulin A nephropathy (IgAN). Atrasentan, an oral endothelin A receptor antagonist, is in Phase III development for IgAN and has shown notable decreases in proteinuria. It is also in early development for other rare kidney diseases. Zigakibart (BION-1301), a subcutaneously administered anti-a proliferation-inducing ligand (APRIL) monoclonal antibody, entered Phase III development for IgAN in July 2023.

“We are excited to complete this important transaction and look forward to leveraging our combined resources and expertise to further advance the development of these promising treatments for the benefit of patients with rare, severe chronic kidney diseases,” said Vas Narasimhan, CEO of Novartis, in the press release. “We welcome the Chinook team to Novartis as we expand our renal portfolio and continue our journey to reimagine medicine.”

Novartis has completed its acquisition of biopharma company Chinook Therapeutics.  

Novartis Finalizes Chinook Therapeutics Acquisition in Deal Worth Up to $3.5 Billion

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On Aug. 4, 2023, FDA released a guidance document, 

Recommended Acceptable Intake Limits for Nitrosamine Drug Substance-Related Impurities (NDSRIs)

. The guidance gives both applicants and manufacturers of drugs recommendations for estimating the mutagenic and carcinogenic potential of NDSRIs that could be in drug products and gives acceptable intake (AI) limits for NDSRIs.

NDSRIs are a subcategory of nitrosamine impurities that share structural similarity to the API in drug products; NDSRIs often lack the compound-specific mutagenicity and carcinogenicity data necessary for informed safety assessments. FDA wrote in the guidance document that this guidance “provides a recommended methodology for AI determination that uses structural features of NDSRIs to generate a predicted carcinogenic potency categorization and corresponding recommended AI limit that manufacturers and applicants can apply, in the absence of other FDA-recommended AI limits, in their evaluation of potential impurities in their drug products.”

FDA wrote that it will provide updated NDSRI-specific information on 

 to be viewed in tandem with the guidance. The updated information will include suggested AI limits for specific NDSRIs based on “compound-data or read-across analysis from a surrogate”, suggested interim AI limits for NDSRIs, suggested testing methods for corroborative testing of specific NDSRIs, and suggested safety testing methods for NDSRIs. It will also include suggested AI limits for specific NDSRIs based on “predicted carcinogenicity potency categorization listed by APIs that hypothetically could be at risk of forming such NDSRIs.” 

The guidance can help both applicants and manufacturers limit the mutagenic and carcinogenic potential of NDSRIs.

FDA Releases Guidance on Intake Limits for Nitrosamine Drug Substance-Related Impurities

On Aug. 4, 2023, FDA approved zuranolone (Zurzuvae), an oral medication to treat postpartum depression (PPD) in adults from Sage Therapeutics, a US-based biopharmaceutical company. According to an agency press release, zuranolone is the first oral treatment approved for PPD.

The approval was based on two studies that showed zuranolone’s effectiveness as a treatment for PPD. Patients who took zuranolone showed noticeably more improvement compared to those in the placebo groups, and the effect remained four weeks after the last dose of zuranolone.

PPD is a major depressive episode that usually occurs after childbirth, although it can also start in the later stages of pregnancy. As with other forms of depression, PPD can cause sadness, lethargy, and loss of interest in previously enjoyable activities. Symptoms include feelings of sadness or inadequacy, loss of energy, cognitive impairment, and suicidal ideation. Until this approval, PPD treatment was only available via intravenous injection given by a health care provider in a health care facility. FDA granted the application for Zurzuvae priority review and fast track designation.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness—even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” said Tiffany R. Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, in FDA’s press release. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The new drug could be a powerful tool for patients suffering depressive symptoms after birth.

FDA Approves First Oral Treatment for Postpartum Depression

In a press release on Aug. 8, 2023, Lisata Therapeutics announced FDA’s Orphan Drug Designation had been granted to LSTA1 for the treatment of malignant glioma. Lisata Therapeutics is a clinical-stage pharmaceutical company developing therapies for advanced solid tumors and other major diseases. The company created LSTA1 to activate a new uptake pathway, allowing co-administered or tethered antineoplastic drugs to combat solid tumors more successfully. The drug can also modify the tumor microenvironment to make tumors more vulnerable to immunotherapies.

LSTA1 is currently undergoing multiple global studies in a range of solid tumor types in combination with a range of antineoplastic regimens. In the near future, Lisata plans to collaborate with researchers from the University of Tartu in Estonia to conduct a clinical study evaluating LSTA1 in previously untreated glioblastoma multiform (GBM). The company plans to study the impact of LSTA1 when added to standard-of-care (SoC) to treat GBM. The study will be conducted at multiple sites in Estonia and Latvia, with an estimate of 30 patients (with a randomization of 2:1 LSTA1 + SoC vs placebo + SoC). Lisata expects the first patient will be treated in the fourth quarter of 2023.

“Malignant glioma is one of the most aggressive and deadly malignancies,” said Kristen K. Buck, M.D., executive vice president of R&D and chief medical officer of Lisata, in a company press release. “This Orphan Drug Designation acknowledges the high unmet medical need of this patient population as well as the potential of LSTA1 to benefit patients in this setting.”

The Orphan Drug Designation is given by FDA to drugs or biologics designed to treat a rare disease or condition that affects fewer than 200,000 individuals in the United States. These designations create fiscal incentives for clinical development and a seven-year period of US market exclusivity if FDA approval is met. A large amount of non-clinical data suggests that LSTA1 enhances a range of antineoplastic therapies; LSTA1 also showed positive safety, tolerability, and activity in clinical trials enhancing standard-of-care chemotherapy for pancreatic cancer. Lisata anticipates LSTA1 will assist with a range of treatments to treat solid tumors more effectively.

The investigational drug was developed to activate a novel uptake pathway, allowing antineoplastic drugs to combat solid tumors more successfully.

FDA Grants Orphan Drug Designation to Treatment of Malignant Glioma 

On August 1, 2023, FDA warned consumers that two lots of Tydemy (drospirenone/ethinyl estradiol/levomefolate calcium), a prescription oral contraceptive manufactured by Lupin Pharmaceuticals, could be less effective because of lower levels of ascorbic acid, an active ingredient, in the product. These lots (L200183 and L201560) were dispensed in the United States from June 3, 2022, to May 31, 2023. The reduced effectiveness could result in unexpected pregnancies. FDA wrote that as of August 1, 2023, FDA “has not received any reports of adverse events related to using this product.”

On July 29, 2023, Lupin warned its consumers about its 

voluntary recall of the two lots of Tydemy

. Lupin is notifying its wholesalers, drug chains, distributors, supermarkets, and mail order pharmacies via phone and recall notification to arrange the return of all recalled product lots. The company advised patients to keep taking their medication, but to immediately contact their health care professional about alternative contraceptive methods. Wholesalers, distributors, and retailers that have the recalled Tydemy should stop distribution of the recalled product immediately. Lupin had formerly voluntarily recalled the two lots of Tydemy at the wholesale level.

FDA wrote that it encourages healthcare professionals and patients to report any adverse events or quality issues with these or any medications to FDA’s 

Lower levels of an active ingredient may result in unexpected pregnancies. 