LONDON – Morphosys AG finally has some heft to put behind its U.S. commercialization ambitions following FDA approval for its long-nurtured anti-CD19 antibody, Monjuvi (tafasitamab-cxix) in relapsed or refractory diffuse large B-cell lymphoma (r/rDLBCL).

The FDA decision, based on an 81-patient open-label phase II study, is the first approval for a second-line treatment in patients who have progressed during or after initial therapy, and who are too weak for an autologous stem cell transplant.

That gives Morphosys and its commercialization partner, Incyte Corp., a U.S. market of approximately 10,000 patients per year to address.

The two companies have a 50-50 interest after the signing in January of a deal in which Incyte paid $750 million up front, bought $150 million of Morphosys stock and agreed to pay up to $1.1 billion in milestones. In addition to a 50% share of the U.S. market, Incyte acquired 100% of the ex-U.S. rights.

The approval marks an important step in Morphosys’ transformation from R&D-focused into a fully-fledged biopharmaceutical company, Jean-Paul Kress, CEO of the Planegg, Germany-based company, told BioWorld. “This is what we are achieving today with the launch of Monjuvi,” he said.

Jean-Paul Kress, CEO, Morphosys

Kress has been preparing the company for approval of Monjuvi since taking up the role of CEO in September 2019, when his predecessor and co-founder of Morphosys, Simon Moroney, stepped down after 27 years at the helm.

U.S. commercial infrastructure is in place, as are supplies of Monjuvi, which is manufactured in Germany by Boehringer Ingelheim. Germany’s deft management of the COVID-19 pandemic meant there has been no disruption to the supply chain, and while marketing and promotion will now have to be more digital than face-to-face, preparations are complete, Kress said. “We have a team in Boston ready to launch.”

For Incyte, this is the chance to pick up some pace after the phase III failure in January of its JAK1 inhibitor, itacitinib, in acute graft-vs.-host disease. The approval of Monjuvi in combination with Revlimid (lenalidomide) is the beachhead to a larger franchise, with the partners also developing the product in first-line DLBCL, as well as follicular lymphoma, marginal zone lymphoma and chronic lymphocytic leukemia.

Wilmington, Del.-based Incyte will also conduct combination studies of its investigational PI3K-delta inhibitor, parsaclisib, and Monjuvi in r/r B-cell malignancies.

For the discoverer of Monjuvi, Xencor Inc., the approval triggers a $25 million milestone payment from Morphosys, under a 2010 license agreement between the two. Monjuvi follows Alexion Inc.’s Ultomiris (ravulizumab-cwvz) as the second product based on Monrovia, Calif.-based Xencor’s cytotoxic antibody platform.

The technology involves an engineered Fc domain that mediates B-cell lysis through apoptosis, antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis. Xencor also is eligible to receive sales royalties and is in line for additional milestones based on further approvals and extensions of the label.

The commercialization teams “are reaching out to payers starting today,” said Roland Wandeler, chief operating officer of Morphosys. The two companies have “sought to thoughtfully price” Monjuvi, balancing unmet need against the innovation it represents, he said. The wholesale price is set at $16,500 per month for the first year of therapy, reducing to $13,000 per month subsequently, when fewer doses are required.

A program of financial support is to be established to lower the patient access barrier.

Monjuvi represents an important addition to available treatments, and the Incyte and Morphosys sales teams are aligned in the priorities for the launch, said Barry Flannelly, Incyte’s general manager, North America. In the face of COVID-19-enforced restrictions on physical meetings, Incyte will be able to draw on its existing relationships with prescribers, he said.

In an analyst note, SVB Leerink Research said the label on Monjuvi “represents the best-case scenario in our view,” including second-line use and clean safety language without a black box warning. “We believe the CAR T-like efficacy demonstrated by [Monjuvi], as well as its favorable safety profile should enable broad adoption in the second-line setting.”

Unmet need apparent

Given the label, SVB Leerink analysts expect the product to be preferred over Roche Holding AG’s competitor product, the antibody-drug conjugate Polivy (polatuzumab vedotin-piiq), which in any case is approved only as a third-line therapy in the U.S.

Kress said he also believes the safety profile and ease of administration will position Monjuvi ahead of CAR T therapies. “CAR Ts are an important part of the treatment landscape, but they have limitations. Monjuvi is more friendly, being a monoclonal antibody,” he said.

Between 70% and 80% of r/rDLBCL patients are cared for by community oncologists, who do not have access to the resources of academic centers that typically administer “more complicated CAR T therapy,” said Kress.

As the first FDA-approved product for second-line therapy, Monjuvi has the potential to change the standard of care in r/rDLBCL, said Hervé Hoppenot, CEO of Incyte. That patient population currently “is poorly served if not suitable for autologous stem cell transplant. The unmet need is therefore apparent,” Hoppenot said.

The approval “is only the first step in an ambitious program,” with Monjuvi filed with the EMA, and a pivotal study of Monjuvi as first-line therapy in DLBCL due to get underway at the start of next year, along with ongoing trials in other indications, said Hoppenot.

The phase II L-Mind study on which the FDA approval is based showed an overall response rate of 55%, including a complete response rate of 37% and a partial response rate of 18%. The median duration of response at the data cut-off in November 2018 was 21.7 months.

In May, Incyte published longer term follow-up results, based on a November 2019 cut-off. Those showed the complete response rate had risen to 41.3%. At that point, median duration of response was 34.6 months. In the event, the FDA excluded 10 of the 81 patients because they did not have a DLBCL diagnosis confirmed by central pathology, meaning the approval is based on 71 patients.

To add weight to the open-label study, the FDA submission included a retrospective proxy control, looking at the response of patients who received Revlimid alone, in order to isolate the contribution of Monjuvi.

Although the EMA has accepted the Monjuvi file for review, it is known to frown on approving products that have not been in controlled studies. The two companies believe the relatively benign safety profile and the unmet medical need will sway the agency in this case.

“The reaction so far from EMA is very encouraging,” said Steven Stein, Incyte’s chief medical officer. “Based on the high unmet medical need we are quite optimistic EMA will look at the data in a positive way.”