US regulator wipes the smile off Immunomedics’ face

Issues with manufacturing, not exactly a new problem for Immunomedics, derail the company’s bid for glory.

Just when Immunomedics thought it had drawn a line under ongoing production issues, and welcomed an arbitrator’s denial of two of three claims made by its ousted former management team, the US FDA dealt it a fresh blow.

A complete response letter for sacituzumab govitecan, its lead project, has shocked investors who had been led to believe that the manufacturing problems behind the drug should have been dealt with. Even if a quick resubmission is possible the prospect of a protracted US government shutdown could derail the process further.

The non-approvability issues in the letter “were exclusively focused on chemistry, manufacturing and control matters”, Immunomedics said in a statement. For some followers of the company this will be an unpleasant case of déjà vu, and management’s failure to remedy what was a known problem looks poor.

Manufacturing sacituzumab has long been Immunomedics’ Achilles’ heel. Last year the FDA slapped the company with a so-called Form-483, signifying that a site inspection had brought up matters that had to be rectified.

Issues addressed?

On an investor call today Immunomedics insisted that, though it had not seen the reinspection report, it thought it had addressed all the issues raised in the Form-483. It had earlier said that those issues were not material, which is why they were not press-released, and that they could have been resolved as pre- or post-approval commitments.

This probably explains why the markets had largely expected a green light for sacituzumab, which was to have made official the turnaround in Immunomedics’ fortunes and given the company its first approved drug in 37 years of existence, as Stat pointed out. The stock opened off 40% this morning.

Wells Fargo analysts wrote that, in addition to the time needed to fix the problems, there could be a further six-month review if a class 2 resubmission was necessary – something Immunomedics did not rule out. The company said it was unclear whether the continuing US government shutdown would delay a follow-up FDA meeting.

It had filed sacituzumab for third-line triple-negative breast cancer (TNBC) under accelerated approval, based on phase I/II data showing a 31% remission rate. The project is an antibody-drug conjugate targeting Trop-2, an antigen believed to be overexpressed on some tumours. This is the same strategy that lies behind Daiichi Sankyo’s DS-1062, which entered phase I in NSCLC last year.

A separate sacituzumab TNBC trial, Ascent, will measure progression-free survival as primary endpoint and is to provide full approval. Immunomedics insisted that the FDA had not asked for any new preclinical or clinical data, and this included anything from ongoing clinical studies.

Reinvigorated

Until yesterday the company was enjoying the support of a reinvigorated investor base. Even accounting for the fall from grace that all of biotech suffered in the second half of last year, yesterday’s closing price put its stock 120% above where it had stood in May 2017, during an acrimonious shareholder battle.

That had been triggered when Seattle Genetics attempted to license sacituzumab for $250m up front. But the activist investor Venbio managed to scupper the deal and seize control of Immunomedics from its then-management team (Venbio completes its Immunomedics rout, May 5, 2017). A final arbitration ruling in a dispute against the founder and ex-chief executive was made three days ago.

To support commercial sacituzumab supply Immunomedics had secured three manufacturing partners: Samsung Biologics to make the antibody, Johnson Matthey for the linker and BSP Pharmaceuticals for conjugation, fill and finish.

At the JP Morgan conference last week the group boasted of sacituzumab representing a “pipeline in a drug”. Additional uses represent part of the $2.3bn of 2024 sales forecast by EvaluatePharma sellside consensus, though problems clearly have yet to be resolved before even part of this becomes reality.

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