Good morning, myeloma world.

It's just Tuesday, and already the week is getting in­ter­est­ing. We'll be reporting on just two myeloma-related news items today, but one of them is the kind of news we don't see here at Myeloma Morning ^[1] very often.

In particular, the German bio­tech com­pany MorphoSys has sued Janssen Biotech and Genmab, the two com­pa­nies that have devel­oped and mar­keted Darzalex ^[2] (dara­tu­mu­mab). MorphoSys contends that sales of Darzalex infringe on a MorphoSys patent.

In addi­tion, we report on a study that came out last week with results of a Phase 1 trial testing CUDC-907 ^[3], an inves­ti­ga­tional drug, in re­lapsed lym­phoma and multiple myeloma patients. Based on results of the trial, the com­pany devel­op­ing CUDC-907 plans to test it further in patients with a specific type of lym­phoma. The com­pany has not publicly said what its plans are re­gard­ing further devel­op­ment of the drug as a poten­tial treat­ment for multiple myeloma.

MorphoSys Sues, Claims Darzalex Infringes One Of Its Patents

The German bio­tech com­pany MorphoSys yesterday filed a patent infringement suit related to Darzalex (see related MorphoSys press release ^[4]). The suit was filed in the United States District Court for Delaware.

MorphoSys is seeking damages from Janssen Biotech, a division of Johnson & Johnson, and the Danish com­pany Genmab, due to the manu­fac­tur­ing, mar­ket­ing, and use of Darzalex. These activities, MorphoSys claims, infringes its U.S. patent 8,263,746 ^[5], “Anti-CD38 human anti­bodies and uses thereof.”

Before we say any­thing else, we should make it clear that this suit will have no im­medi­ate impact on the avail­a­bil­ity of Darzalex. The filing of the suit is just the first step in a process that is likely to extend over several years. Moreover, it is highly unlikely – again, highly unlikely – that at any point during the suit, or after its conclusion, Darzalex will be­come unavailable due to this legal matter.

Darzalex initially was devel­oped by Genmab, but the drug is now mar­keted by Janssen under an agree­ment it has with Genmab. Darzalex was approved by the U.S. Food and Drug Admin­istra­tion ^[6] last No­vem­ber for the treat­ment of re­lapsed multiple myeloma, and is ex­pec­ted to be approved in Europe ^[7] within three months for a similar use.

Darzalex is a CD38 mono­clonal anti­body ther­apy, meaning that it attacks myeloma cells by taking ad­van­tage of the fact that the cells have CD38 proteins on their surface. The MorphoSys patent mentioned in its suit is related to ther­a­pies that work in this way.

MorphoSys itself has been devel­op­ing a CD38 mono­clonal anti­body, known as MOR202 ^[8], for the treat­ment of multiple myeloma. MorphoSys agreed in 2013 to develop MOR202 together with the U.S. pharma­ceu­tical com­pany Celgene ^[9], which mar­kets the myeloma ther­a­pies Revlimid (lena­lido­mide), Pomalyst (poma­lido­mide, Imnovid), and thalido­mide (Thalomid). Celgene and MorphoSys ended the MOR202 devel­op­ment agree­ment ^[10], how­ever, last year.

The French pharma­ceu­tical com­pany Sanofi also is devel­op­ing a CD38 mono­clonal anti­body, isatuximab ^[11] (SAR650984), for the treat­ment of multiple myeloma.

We spoke to investment analyst Michael Novod, Director of Healthcare Equity Research at the Swedish fi­nan­cial services com­pany Nordea, about the MorphoSys lawsuit. Mr. Novod covers Genmab for Nordea and recently wrote a re­search note about the MorphoSys suit.

Mr. Novod said that, given how early it is in the process, not many details about the merits of the MorphoSys case are known. In his opinion, how­ever, it would be surprising if the suit had a high likelihood of success. Johnson & Johnson almost cer­tainly did extensive due diligence prior to its agree­ment with Genmab to acquire global mar­ket­ing rights for Darzalex.

Mr. Novod also emphasized that MorphoSys is not arguing in its lawsuit that any Genmab patents related to Darzalex are invalid (and there are many Genmab patents related to Darzalex). Instead, the MorphoSys lawsuit claims only that Janssen and Genmab are infringing on a MorphoSys patent.

If over time MorphoSys's patent claim is found to have some merit, Mr. Novod says that pre­vi­ous cases that are similar sug­gest that MorphoSys probably would gain the right to a royalty on Darzalex sales in the low single to middle single digit per­cent­age point range.

A rep­re­sentative of Janssen told The Beacon that Janssen and Johnson & Johnson “disagree with the alle­ga­tions made by MorphoSys in its complaint for patent infringement related to CD38 anti­bodies, and we in­tend to vigorously contest those alle­ga­tions.”

A Genmab rep­re­sentative said that the com­pany does not comment on ongoing lit­i­ga­tion, but it sup­ports the assess­ment of its partner, Janssen, in terms of disagreeing with the alle­ga­tions made by MorphSys in its complaint for patent infringement related to CD38 anti­bodies.

MorphoSys spokeswoman Claudia Gutjahr-Löser told The Beacon that, due to legal con­sid­er­a­tions, she could not say much about her com­pany's lawsuit. When asked, how­ever, about the timing of the lawsuit – which occurred after Darzalex had been under devel­op­ment for a number of years – Dr. Gutjahr-Löser said that MorphoSys could not legally dem­onstrate injury due to patent infringement until Darzalex was FDA approved and being sold on the mar­ket.

Dr. Gutjahr-Löser also noted that the lawsuit was motivated by the desire to pro­tect the intellectual property rights of MorphoSys scientists. MorphoSys will con­tinue to de­vel­op its pro­pri­e­tary anti­body MOR202 for patients suffer­ing from multiple myeloma and other dis­eases.

Results of CUDC-907 Phase 1 Clinical Trial

A group of U.S. re­searchers last week reported results from a Phase 1 clin­i­cal trial testing CUDC-907 as a poten­tial treat­ment for re­lapsed lym­phoma and multiple myeloma (abstract ^[12]). Based on the results of the trial, the com­pany devel­op­ing CUDC-907 has decided to test the drug further in a Phase 2 trial for patients with diffuse large B-cell lym­phoma (press release ^[13]). It is not clear at this time whether there are any im­medi­ate plans to in­ves­ti­gate the drug further as a treat­ment for multiple myeloma.

CUDC-907 is a unique drug in that it belongs to two classes of ther­a­pies. It is an HDAC in­hib­i­tor and a PI3K in­hib­i­tors. Farydak ^[14] (panobinostat), which was approved last year by the FDA as a new treat­ment for multiple myeloma, is an HDAC in­hib­i­tor. Zydelig (idelalisib), which is used to treat a form of leukemia, is a type of PI3K in­hib­i­tor.

The study published last week summarizes results of the dose escalation phase of a Phase 1 trial testing CUDC-907 in 44 re­lapsed lym­phoma and myeloma patients. To par­tic­i­pate in the trial, patients had to have had two pre­vi­ous treat­ment regi­mens.

There were only four multiple myeloma patients in the trial. These four patients were heavily pre­treated, having had a median of 7 prior lines of ther­apy. Two of the four patients achieved stable dis­ease in re­sponse­ to CUDC-907 treat­ment. In one case, the stable dis­ease lasted for an extended period of time. The other two myeloma patients did not register a re­sponse­ to CUDC-907 treat­ment; their dis­ease progressed further.

Across all patients in the study, the most common serious side effects observed during the trial were low platelet levels, low neu­tro­phil levels, and high blood sugar levels. The drug showed evi­dence of efficacy in a subgroup of lym­phoma patients with diffuse large B-cell lym­phoma (DLBCL), and Curis, the com­pany devel­op­ing CUDC-907, has said that it will conduct a Phase 2 trial of the drug in patients with that form of lym­phoma.

Curis has not said whether it has any plans to de­vel­op CUDC-907 further as a treat­ment for multiple myeloma. The issue is not addressed in the press release the com­pany issued in regard to publication of the Phase 1 trial results, and com­pany rep­re­sentatives did not respond to an email from The Beacon asking about the firm's plans for CUDC-907 in multiple myeloma.

That said, myeloma specialist Dr. Paul Richardson of the Dana-Farber Cancer Institute, writing in an editorial accompanying the CUDC-907 study, sug­gests it would make sense to further in­ves­ti­gate CUDC-907 in multiple myeloma. He notes that there were some re­sponse­s to the drug among the myeloma patients in the trial, even though the patients had been heavily pre­treated. In addi­tion, drugs such as CUDC-907 often work better in com­bi­na­tion with other myeloma ther­a­pies, and this should be explored.

In particular, Dr. Richardson wrote that:

“The pri­mary emphasis for the future of CUDC-907 will be for the treat­ment of DLBCL, but these data sug­gest that further exploration of this agent in com­bi­na­tion with other drugs for the treat­ment of re­lapsed or re­frac­tory multiple myeloma might be useful …

“In the patients with myeloma, stable dis­ease was reported, which, given their re­lapsed or re­frac­tory char­ac­ter­istics and pre­vi­ous exposure to HDAC in­hib­i­tors, sug­gests that this particular oral agent in com­bi­na­tion with other drugs might be of particular interest in re­lapsed or re­frac­tory myeloma. Specifically, combinatorial strategies have shown sub­stan­tial benefit, with stable dis­ease seen with mono­therapy with other oral agents such as panobinostat [Farydak], vorinostat [Zolinza], and next-generation HDAC in­hib­i­tors in­clud­ing ricolinostat. Thus the promise of this particular oral agent extends beyond the lym­phomas, and given the attractive aspects of its biology, broader studies are warranted.”

(According to a presentation poster ^[15] from last year's annual meeting of the American Society of Clinical Oncology, at least 9 multiple myeloma patients were enrolled in both the dose escalation and extension phase of the CUDC-907 Phase 1 clin­i­cal trial. Responses for three of the patients were not evaluable at the time the poster was prepared. Among the other six patients for whom re­sponse­ data were avail­able, four achieved stable dis­ease as a best re­sponse­, and two ex­peri­enced dis­ease pro­gres­sion.)

New Myeloma-Related Research Articles

1. Gupta, N. et al., “Exposure-safety-efficacy analysis of single-agent ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma: dose selection for a phase 3 maintenance study” in Investigational New Drugs, April 2, 2016 (full text ^[16])
2. Younes, A. et al., “Safety, tolerability, and preliminary activity of CUDC-907, a first-in-class, oral, dual inhibitor of HDAC and PI3K, in patients with relapsed or refractory lymphoma or multiple myeloma: an open-label, dose-escalation, phase 1 trial” in Lancet Oncology, March 31, 2016 (abstract ^[12])