FDA Action Alert: Dynavax, Ascendis and BMS

FDA Action Alert_Taylor Tieden for BioSpace

Pictured: A scientist with pill bottles in front of FDA headquarters/Taylor Tieden for BioSpace

May will be relatively slow for the FDA as there are only four key action dates. Among other announcements, the regulator will release its rulings on a hepatitis B vaccine for adults on hemodialysis and two possible indications for BMS’s CAR-T therapy Breyanzi.

Read below to find out more.

Dynavax proposes hepatitis B vaccine for hemodialysis patients

Today is the day the FDA is expected to release its decision on Dynavax Technologies’ sBLA, which seeks to expand approval of the hepatitis B vaccine Heplisav-B for use in hemodialysis patients.

Heplisav-B received its first U.S. approval in 2017 to prevent hepatitis B, caused by all known subtypes of the virus, in adults 18 years and older. According to the label, Heplisav is a recombinant protein vaccine composed primarily of the hepatitis B surface antigen that can prepare the body to protect against infection with the virus.

Heplisav-B is intended to be administered in two doses and is the only approved hepatitis B vaccination that completes the vaccination series in one month. The UK Medicines and Healthcare products Regulatory Agency granted Heplisav-B marketing authorization in February 2023.

Dynavax reported that Heplisav-B brought in net sales of $213 million in 2023, up 69% from the previous year. At the end of December 2023, Heplisav-B controlled approximately 42% of the US hepatitis B vaccine market, up from 35% at the end of 2022.

In a statement on the company’s full-year results, CEO Ryan Spencer said Heplisav-B experienced “record revenue growth” in 2023 and became the “market share leader in two largest growth segments.” These successes will help Dynavax establish Hepliav-B as “the leading vaccine in the U.S. adult hepatitis B vaccine market,” he said.

The company expects further growth for Heplisav-B in 2024, anchored by upcoming potential approval. Dynavax forecasts net product sales of $265 million to $280 million for Heplisav-B this year.

Ascendis is again attempting to obtain hypoparathyroidism approval for TransCon PTH

The FDA is expected to release its ruling on May 14 on Ascendis Pharma’s reapplication of its investigational drug TransCon PTH (palopegteriparatide), proposed for the treatment of adults with hypoparathyroidism.

TransConPTH is a parathyroid hormone prodrug designed for oral availability and long-term action, working by restoring physiological hormone levels for 24 hours a day. This mechanism of action could potentially make it possible to counteract hypoparathyroidism, a rare disorder characterized by a deficiency of parathyroid hormone, which in turn leads to low calcium and high phosphate levels.

Patients with hypoparathyroidism experience weakness, muscle cramps, and headaches, and the condition can lead to long-term complications such as calcium deposits in the eyes, brain, and kidneys. Currently, hypoparathyroidism is treated by high-dose therapy with calcium and active vitamin D, which does not optimally control the condition.

Ascendis first submitted a drug application for TransCon PTH in 2022, which the FDA rejected in May 2023, citing manufacturing concerns. The regulator found no problems with the drug’s safety or effectiveness and did not require additional studies.

Currently, TransCon PTH is approved in the United Kingdom and the European Union, where it is marketed under the brand name Yorvipath.

BMS expects two rulings for the CAR-T therapy Breyanzi

To close out the month, BMS is considering two planned action dates for its CAR-T therapy Breyanzi (lisocabtagene maraleucel): May 23 for relapsed or refractory follicular lymphoma (FL) and May 31 for relapsed or refractory mantle cell lymphoma (MCL). .

In Florida, Breyanzi is supported by the single-arm Phase II TRASCEND FL trial, which is the largest clinical trial to date evaluating CAR-T therapy in relapsed or refractory indolent non-Hodgkin lymphoma, including FL, with 213 patients enrolled.

BMS presented data from TRANSCEND FL in December 2023 showing that Breyanzi produced a complete response rate of 95.7% in patients with relapsed or refractory high-risk FL when used in second-line therapy. The median progression-free survival had not yet been reached at this point.

Meanwhile, BMS supports Breyanzi’s MCL application with findings from the MCL cohort of the TRANSCEND NHL 001 study. Published in December 2023 in Journal of Clinical OncologyResults from the pivotal Phase I study demonstrated a significant and clinically meaningful response to treatment in heavily pretreated patients, most of whom achieved a complete response.

Breyanzi is a CAR T-cell therapy that targets the CD19 surface protein, which is commonly expressed on B cells. Once bound to CD19, Breyanzi proliferates and induces the release of pro-inflammatory cytokines and cell death in cancer cells. The FDA first approved Breyanzi in February 2021 for the treatment of relapsed or refractory B-cell lymphoma.

In March 2024, Breyanzi received two new approvals, one for chronic lymphocytic leukemia and the other for small lymphocytic leukemia.

Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Contact him on LinkedIn or email him at [email protected] or [email protected].