Daria G. Husni

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On Sept. 20, 2023, Alexion, AstraZeneca’s rare disease group, completed the purchase and license agreement for a portfolio of preclinical rare disease gene therapy programs and enabling technologies from Pfizer. The acquisition cost AstraZeneca up to $1 billion, with the addition of tiered royalties on sales.Alexion hopes to create new genetic therapies, improving their safety and efficacy; the portfolio will bolster Alexion and AstraZeneca’s current work on genomic medicine.

Alexion entered into the agreement with Pfizer near the end of July 2023. The profile included sever novel adeno-associated virus (AAV) capsids, which have demonstrated to be effective for delivering therapeutic gene cargos for gene therapy and gene editing. Alexion reported that several Pfizer employees associated with the portfolio will join Alexion’s team as employees.

Alexion was formed as a group within AstraZeneca that focuses on rare diseases, following AstraZeneca’s acquisition of Alexion Pharmaceuticals in 2021. Alexion centers its research on novel molecules, focusing on the complement cascade and its development efforts on hematology, nephrology, neurology, metabolic disorders, cardiology, and ophthalmology.

, Marc Dunoyer, chef executive office at Alexion, said, “Today’s announcement represents another major step forward in Alexion and AstraZeneca’s ambition to be an industry leader in genomic medicine, which has potential to be transformative and even curative for patients with devastating diseases. We look forward to continuing our work to develop enhanced platforms and technologies with broad therapeutic application while integrating best-in-class expertise to accelerate promising therapeutics into the clinic.”

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The AstraZeneca rare disease group hopes to use these new gene therapy programs to bolster its work on genomic medicine.

Alexion Completes Purchase and License Agreement of Rare Disease Gene Therapy Portfolio from Pfizer

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On Sept. 15, 2023, GSK announced that its myelofibrosis treatment, Ojjaara (momelotinib) had been approved by FDA. The approval covers treatment of intermediate or high-risk myelofibrosis in adults with anemia, regardless of prior therapies. According to GSK, this is the first and only treatment for myelofibrosis patients with anemia. Nearly every myelofibrosis patient will develop anemia, and over 30% discontinue their myelofibrosis treatments due to it. Ojjaara also treats constitutional symptoms and splenomegaly (enlargement of the spleen).

Ojjaara is a once-a-day, oral JAK1/JAK2 and activin A receptor type 1 (ACVR1) inhibitor. It works along three key signaling pathways: Janus kinase (JAK) 1, JAK2, and activin A receptor type 1 (ACVR1). Inhibition of JAK1 and JAK2 can improve constitutional symptoms and splenomegaly, while inhibition of ACVR1 can decrease levels of the protein hepcidin, which contribute to anemia and are elevated in myelofibrosis. GSK held two Phase III, multicenter, randomized, double-blind studies testing the efficacy of Ojjaara in comparison to two other inhibitors used to treat myelofibrosis, danazol and ruxolitinib. Critically, while danazol and ruxolitinib can treat constitutional symptoms and splenomegaly associated with myelofibrosis, neither of them have been able to treat anemia.

Myelofibrosis is a rare blood cancer that can lead to severely low blood counts, which include anemia and thrombocytopenia. GSK stated that around 40% of patients have moderate to severe anemia at the time of diagnosis, and nearly all patients develop anemia while suffering from the disease. Treatment for myelofibrosis patients with anemia often involves blood transfusions, and more than 30% of patients discontinue myelofibrosis treatment because of anemia. Those that depend on transfusions often have a shortened survival rate. GSK hopes that by targeting anemia, it will make a “significant difference in the treatment regimen for these patients who have limited options to address these aspects of the disease.”

Anemia, experienced by most myelofibrosis patients, has caused over 30% of patients to discontinue their treatment.  

FDA Approves Treatment for Myelofibrosis Patients with Anemia

On Sept. 18, 2023, Cellectar Biosciences announced that its treatment for Waldenstrom’s macroglobulinemia, Iopofosine, had been granted Priority Medicine (PRIME) status by the European Medicines Agency (EMA). Iopofosine is the company’s lead small-molecule drug candidate, meant to treat Waldenstrom’s macroglobulinemia (WM) in patients who have completed two or more prior treatment regimens. It is created to give targeted delivery of idodine-131 directly to cancer cells, limiting the exposure to healthy cells. 

Waldenstrom’s macroglobulinemia is a cancer of the lymphatic system, or lymphoma, which is rare and incurable. It occurs in a B-lymphocyte or B-cell, a type of white blood cell that normally grows into a plasma cell to manufacture antibodies that help fight infections. In WM, a hostile change to the B-cell occurs during the late stages of maturing, causing the cell to multiple into a clone of identical cells. These cells are primarily in the bone marrow, but they also inhabit the lymph nodes and other tissues and organs of the lymphatic system. They produce an abundance of antibodies that build up in the body, causing a variety of issues.

Iopofosine previously received Fast Track designation in the United States from FDA for WM patients who have received two or more previous treatment regimens, as well as relapsed/refractory multiple myeloma and relapsed/refractory diffuse large B-cell lymphoma. EMA has previously granted an Orphan Drug Disease Designation for relapsed/refractory multiple myeloma and Waldenstrom’s macroglobulinemia.

Iopofosine provides targeted delivery of idodine-131 directly to cancer cells.

EMA Grants Priority Medicine Status to Cellectar’s Waldenstrom Macroglobulinemia Treatment

In a European Medicines Agency (EMA) press release on September 9, 2023, the agency’s Pharmacovigilance Risk Assessment Committee (PRAC) outlined new measures to avoid fetus exposure to topiramate-containing medicines. Topiramate is known to cause serious birth defects if used during pregnancy, and medicines containing it may increase the risk of neurodevelopmental problems in children. In the European Union, topiramate-containing medicines are used to treat epilepsy and prevent migraines; in some EU countries they are also used with phentermine for weight loss.

As of the publication of this article, PRAC recommends that unless there is no other treatment available, patients using topiramate to treat epilepsy should not use the medication while pregnant. Topiramate must not be used to prevent migraines or manage body weight while pregnant, and patients who are able to become pregnant must use birth control while taking topiramate. PRAC also recommends a pregnancy prevention program to inform those able to become pregnant of the risks associated with topiramate exposure in the womb.

Regardless of indication, topiramate should only be used by patients who can become pregnant when the following conditions are met:

the patient must take a pregnancy test before starting treatment

they must receive counseling on the risks of topiramate treatment during pregnancy

they must complete an annual risk awareness form during treatment.

These recommendations follow PRAC’s review of three recent observational studies, two of which suggest that children exposed to topiramate in the womb have a two- to three-fold higher risk of neurodevelopmental disorders. PRAC consulted with a group of experts, patient representatives, and specialists during the review. Companies marketing topiramate must conduct a drug utilization study, as well as surveys of healthcare professionals and patients, to evaluate the success of the new measures.

The product information for topiramate-containing medicines will be updated, and a visible warning will be added to the packaging of the medicine. Patients and healthcare professionals will also be provided with information on the risks of using the medication during pregnancy, and patients will be given a patient card with each package of the medicine.

A direct healthcare professional communication will be sent to healthcare professionals prescribing, dispensing, or administering the medicine. It will also be published on EMA’s website.

Topiramate can cause serious birth defects if exposed to children in the womb. 

PRAC Recommends New Measures to Avoid Topiramate Exposure in Pregnancy

FDA announced on Aug 30, 2023, that it is creating two compliance policy guidances initiating a year-long stabilization period for those in the pharmaceutical supply chain that need time to adhere to Drug Supply Chain Security Act (DSCSA) requirements for electronic drug tracing at the package level. The policy effects trading partners, mainly manufacturers, wholesale distributors, dispensers, and repackagers. The requirements are scheduled to change on November 27, 2023, and the stabilization period lasts until November 27, 2024.

The DSCSA went into effect in 2013, and outlines the requirements for the electronic tracing and identification of prescription drug distribution in the U.S. It requires trading partners to supply, accept, and maintain documentation on prescription drugs and their chain of ownership in the U.S. supply chain, from manufacturer to dispenser. The current DSCSA requirements as of September 1, 2023, will be changed on November 27, 2023. The new requirements will include mandating that trading partners manage documentation of product and ownership electronically (previously, partners were permitted to do so in paper format).

Enhanced Drug Distribution Security Requirements Under Section 582(g)(1) of the Federal Food, Drug, and Cosmetic Act – Compliance Policies

Wholesale Distributor Verification Requirement for Saleable Returned Drug Product and Dispenser Verification Requirements When Investigating a Suspect or Illegitimate Product —Compliance Policies

 Revision 1 (WDVRS). WDVRS Revision 1 adds a year extension (from November 27, 2023, to November 27, 2024) to a guidance released on October of 2020 that directs distributors to verify product identifiers before distribution. EDDSR covers FDA’s new compliance policies for product tracing at the interoperable, electronic, package level; these policies will go into effect on November 27, 2023.

FDA intends for trading partners to use the stabilization period to “build and validate interoperable systems and processes, manage products and data, and ensure continuity of the supply chain and product availability to patients.” It is not intended as a justification for delaying compliance efforts with the DSCSA.

The new policy will require trading partners to supply, accept, and manage all documentation of product and ownership of prescription drugs electronically.

FDA Establishes Stabilization Period for Updated DSCSA Compliance Policies

On Aug. 30, 2023, Pfizer and BioNTech SE announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended marketing authorization for Omicron XBB.1.5-adapted monovalent COVID-19 vaccine, given as a single dose to those 5 years of age and older. The recommendation comes regardless of COVID-19 vaccination history. Additionally, CHMP recommended the updated vaccine for those 6 months to 4 years old; it would be given as part of or all of the main three-dose vaccination series (depending on prior dosage amount), or as a single dose for individuals with a complete COVID-19 primary vaccination course (or SARS-CoV-2 infection).

The vaccine is based on BioNTech’s messenger RNA (mRA) technology and was developed by both companies. The CHMP’s recommendation relied on previous clinical, non-clinical, and real-world evidence showing the safety and efficacy of COVID-19 vaccines from Pfizer and Biotech. The application also contained pre-clinical data demonstrating the Omicron XBB.1.5-adapted monovalent COVID-19 vaccine has a significantly stronger response against multiple XBB sublineages as compared to the Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine. There was also pre-clinical data showing that the updated vaccine induces serum antibodies that neutralize the recently World Health Organization-designated variant of interest EG.5.1 (Eris).

Once the European Commission finishes its review of the CHMP’s recommendation the improved vaccine with be ready to ship in the EU immediately. The companies have been manufacturing the vaccine to secure supply ahead of the fall and winter season, when COVID-19 vaccination is predicted to increase. Pfizer and BioNTech have also submitted an application with FDA and are expecting a decision soon. The companies have given data to other regulatory authorities worldwide.

“This season’s vaccine is ready to ship as soon as the final regulatory decision is made, so that people across Europe can better help protect themselves against COVID-19 illness as the risk rises,” said Albert Bourla, Chairman and chief executive officer at Pfizer in a Pfizer press release. “It's been nearly a year since many citizens in the European Union were vaccinated against COVID-19 and the updated formulation provides the opportunity for them to receive a vaccine more closely matched to current sublineages."

The updated vaccine will be ready to ship following a positive European Commission review. 