Editors' (re)View: Hope for BCG alternatives; AdComm casts positive light on SCD therapy

Editor’s note: Welcome to Editors' (re)View, our editors’ takes on things going on in the pharma world that deserve some extra consideration.

Hope on the horizon for unmet needs in bladder cancer

Today we reported that the U.S. FDA has given London-based Prokarium the green light for its lead program in non-muscle invasive bladder cancer (NMIBC). While we typically don’t report on early-stage progress such as IND approvals, given the widespread and serious shortage of generic cancer drugs in the U.S. right now, I want to highlight this milestone.

In the U.S., bladder cancer is the fourth most common cancer in men (less common in women). Fortunately, more than 70% of patients are diagnosed at an early stage (determined by the depth of tumor invasion into the bladder).

Right now, the standard of care is a microbial immunotherapy, Bacillus Calmette-Guérin (BCG), administered into the bladder through a catheter. Merck & Co., the only maker and supplier of BCG, has been experiencing global shortages since 2019. (One study found that because of the shortage, an estimated 8,333 U.S. patients with moderate to advanced bladder cancer aren't receiving optimal care.)

In 2021, Merck announced plans to construct a new manufacturing plant in Durham, North Carolina to expand production capacity for BCG — but also said it would take 5-6 years to complete the facility.

But even if the industry gets beyond the shortages, BCG therapy is associated with significant side effects, as well as high disease recurrence and progression rates. According to Prokarium, despite early diagnosis and treatment with BCG, up to 80% of patients have a recurrence, increasing the risk of progression.

As someone with a close family member with NMIBC who has been on a BCG waiting list for months, I find myself paying  attention to the space, where progress has been slow and still, to some extent, reliant on BCG.

Last year, the FDA approved Ferring Pharmaceuticals’ novel adenovirus vector-based gene therapy, Adstiladrin — marking the first gene therapy approval for bladder cancer. Adstiladrin is approved for the treatment of adult patients with high-risk BCG-unresponsive NMIBC.

Back in May the FDA rejected ImmunityBio's BLA for its drug, Anktiva to be used in combination with BCG, for patients with BCG-unresponsive NMIBC. The drugmaker said the FDA flagged deficiencies related to its inspection of the company's third-party CMO.

It's early days for Prokarium — the company will begin enrolling patients in the PARADIGM-1 phase 1study in the first half of 2024 — but I respect the company’s ambitious goal to transforming the treatment paradigm in a market that has seen little innovation in more 30 years. —Karen Langhauser

AdComm casts positive light on CRISPR, Vertex gene-edited therapy

Yesterday, we reported that the FDA's Cellular, Tissue, and Gene Therapies Advisory Committee had held its meeting for CRISPR Therapeutics and Vertex's exagamglogene autotemcel (exa-cel), designed to treat severe sickle cell disease (SCD) in individuals aged 12 and older experiencing recurrent vaso-occlusive crises.

If approved, exa-cel would become the first CRISPR-based therapy to successfully make it through the regulatory process. During the meeting, the therapy's novelty took center stage. While there were no concerns over safety, some members expressed hesitancy over the companies’ ability to prevent off-target edits. Exa-cel would also be the first genetic therapy for the roughly 20,000 severe SCD patients in the U.S.

The AdComm, although lacking control over regulatory approval, expressed a predominantly positive outlook during the meeting. While some members had reservations, the committee's opinion casts a positive light on the therapy in the wake of the FDA's upcoming decision.

The FDA granted priority review status for exa-cel in SCD treatment, setting a PDUFA action date of December 8, 2023. The companies are also seeking a BLA for exa-cel in transfusion-dependent beta-thalassemia is scheduled for PDUFA review on March 30, 2024.

In this case, things may be looking up for CRISPR and Vertex. — Andrea Corona