FDA Action Alert: Roche, GSK, Regeneron, More

July is a back-heavy month for the FDA, which is expected to deliver eight big decisions by the end of the month. Among these are several applications in blood cancer and a potential comeback for GSK’s antibody-drug conjugate.

Read below for more.

Roche is looking to push its T cell engager Columvi, plus chemotherapy, into earlier lines of treatment, with a supplemental Biologics License Application (sBLA) for the use of the drug in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who have undergone at least one prior line of therapy. The FDA’s verdict is expected by July 20.

Columvi is already indicated for DLBCL, but only in patients who have already been exposed to at least two lines of systemic therapies. The anti-CD20 and -CD3 bispecific antibody can also be used to treat patients with large B cell lymphoma. It carries a boxed warning for cytokine release syndrome.

Roche is using data from the Phase III STARGLO study to support its bid for an expansion. Results showed that when combined with gemcitabine and oxaliplain, Columvi cuts the risk of death by 41%, as compared with a rituximab-based regimen. The Columvi combo also cut the risk of death or disease worsening by 63%.

If approved, Columvi could become an off-the-shelf and fixed-duration treatment option for DLBCL patients, available soon after receiving their diagnosis, as per a December 2024 Roche press release.

By July 22, the FDA is expected to release its decision on Replimune’s BLA for RP1, an oncolytic immunotherapy, for use in combination with Bristol Myers Squibb’s PD-1 blocker Opdivo to treat patients with advanced melanoma.

The RP1 construct consists of a proprietary strain of the herpes simplex virus that has been engineered to carry a fusion protein. RP1 works by directly destroying the cancer cells, while also tweaking the tumor’s microenvironment to stimulate the immune system and activate a systemic anticancer response. Replimune is proposing RP1 as part of a combo regimen for patients who previously failed to see a response on an anti-PD-1 therapy.

Data from the IGNYTE study support RP1’s bid for approval. Data published last month showed an overall response rate of 32.9%, the trial’s primary endpoint. The complete response rate was 15%, while the landmark overall survival rate reached 54.8% at three years.

Replimune will also run the Phase III IGNYTE-3 trial as a confirmatory study for RP1. The program is ongoing.

After a withdrawal in late 2022, GSK is continuing to rebuild its antibody-drug conjugate Blenrep, which the pharma is again proposing for relapsed or refractory multiple myeloma. A decision is expected by July 23.

Blenrep was originally cleared for this indication in August 2020. However, the approval was granted under the regulator’s accelerated pathway, which meant that GSK had to confirm its clinical benefit in a subsequent late-stage study. In November 2022, after disappointing results from the Phase III DREAMM-3 trial, which was supposed to act as Blenrep’s confirmatory study, the pharma pulled the drug from the U.S. market.

Now GSK is giving Blenrep another go, armed with data from the DREAMM-7 and DREAMM-8 trials. In its November 2024 release, the pharma said that both studies demonstrated significant and clinically meaningful improvements in progression-free survival for patients treated with Blenrep versus standard-of-care triplet regimens. A planned interim analysis of DREAMM-7 also showed that Blenrep could improve overall survival in this indication.

In June 2024, buoyed by encouraging findings from DREAMM-7 and DREAMM-8, GSK touted the “multi-blockbuster” potential of Blenrep in multiple myeloma.

Sobi is proposing to use its thrombopoietin receptor agonist Doptelet in children aged one year and older with persistent or chronic immune thrombocytopenia. The FDA’s target decision date is July 24.

Designed to be orally available, Doptelet is a small molecule drug that works by binding to and activating the thrombopoietin receptor, in turn triggering an increase in the production of platelets. This mechanism of action allows Doptelet to address thrombocytopenia in patients with chronic liver disease scheduled for a procedure, for which the drug was approved in 2018.

Doptelet is also approved for adult patients with chronic immune thrombocytopenia who had previously responded suboptimally to treatment. Sobi is seeking to expand this second indication to include children one year and older using data from the AVA-PED-301 trial. According to a December 2024 news release from Sobi, the study showed that Doptelet achieved durable platelet response in this pediatric population.

The FDA has also accepted the application for an oral suspension formulation of Doptelet, though it’s not clear when a verdict is expected.

On or before July 27, the FDA is set to release its verdict on Ascendis Pharma’s growth hormone Skytrofa for use in adult patients with growth hormone deficiency.

The application is backed by data from the Phase III foresiGHt study, a randomized, double-blind and placebo-controlled trial that enrolled nearly 260 adult patients with growth hormone deficiency, symptoms of which can include central obesity, metabolic syndrome and decreased bone density. Results showed a significant reduction in trunk fat at 38 weeks in the Skytrofa arm as compared with placebo. The study also found that Skytrofa-treated patients had significantly better lean mass versus placebo.

Delivered weekly as a subcutaneous injection into the abdomen, thigh or buttock, Skytrofa is a pegylated human growth hormone that elicits various metabolic effects, including stimulating glucose output, protein synthesis and lipolysis in the liver. Skytrofa also facilitates skeletal growth in children with growth hormone deficiency.

Skytrofa was first approved in August 2021.

Apellis Pharmaceuticals is proposing to expand the label of its complement inhibitor Empaveli to cover two rare kidney diseases: C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN). The FDA has set a target decision date of July 28.

Both C3G and IC-MPGN are severe and debilitating kidney conditions linked to excessive accumulation of the complement component 3 (C3c) in the kidney, leading to inflammation, organ damage and ultimately failure. According to an April release from Apellis, a total of around 5,000 people in the U.S. suffer from these conditions.

Delivered via a subcutaneous infusion, Empaveli targets the C3 complement protein, in turn regulating the activity of the complement cascade. This mode of action won the drug an FDA approval in May 2021 for paroxysmal nocturnal hemoglobinuria. Empaveli’s active ingredient, pegcetacoplan, is also approved as an intravitreal injection under the brand name Syfovre for geographic atrophy.

Apellis’ bid for expansion is backed by data from the Phase III VALIANT study, which at 26 weeks demonstrated a statistically significant 68% reduction in proteinuria in Empaveli-treated patients versus placebo. Empaveli likewise lowered C3c levels.

The FDA has a target decision date of July 29 for PTC Therapeutics’ application for sepiapterin, an oral drug being proposed for the treatment of phenylketonuria (PKU) in adults and children.

Sepiapterin boosts the activity of the enzyme phenylalanine hydroxylase (PAH) through two pathways. First, when metabolized, the drug turns into a cofactor critical for the action of PAH. Second, sepiapterin also prevents the misfolding of the PAH protein, ensuring that the enzyme will function properly. This mechanism establishes the drug’s promise for PKU, a rare metabolic disease characterized by the inability to break down phenylalanine, which leads to its toxic buildup across the body.

For its FDA bid, PTC filed data from the Phase III APHENITY study. According to an October 2024 press release from the company, sepiapterin reduced phenylalanine levels by 63%. In those with classical PKU, phenylalanine levels were lowered by 69%. Nearly 85% of patients hit phenylalanine levels below 360 µmol/L, in accordance with PKU treatment guidelines.

In April, the European Union’s Committee for Medicinal Products for Human Use issued a positive opinion for sepiapterin, which will carry the brand name Sephience if approved, endorsing the drug for marketing authorization in the region.

Regeneron is advancing its bispecific T cell engager odronextamab for relapsed or refractory follicular lymphoma, proposing its use in patients who have undergone at least two prior lines of therapy. The FDA is expected to release its verdict on July 30.

The FDA has previously rebuffed Regeneron’s bid in this indication, issuing a Complete Response Letter in March 2024 that cited problems with the enrollment of its confirmatory studies. Regeneron has since fully enrolled the Phase III OLYMPIA-1 trial, opening up a path to resubmission. The company is supporting the application with data from the Phase I and pivotal Phase II ELM-1 and ELM-2 studies, which demonstrate an 80% overall response rate in patients treated with odronextamab, as per the company’s February 2025 news release. The complete response rate hit 74%.