Genmab nabs multiple myeloma lead

Genmab might well be celebrating approval of its anti-CD38 MAb Darzalex four months ahead of schedule, leaving competing agents from Sanofi and MorphoSys eating its dust. But the company and its marketing partner Johnson & Johnson will know that there is more work to be done to open up earlier-stage indications and even greater sales potential.

One stumbling block here, however, could be cost. To be used in earlier lines of multiple myeloma treatment Darzalex might need to be combined with the likes of Revlimid. J&J has priced Darzalex at around $134,000 for the first year of treatment, Genmab’s chief executive told EP Vantage – even higher than the average annual cost of nearly $113,000 per year for Revlimid.

But Darzalex (daratumumab) will be cheaper than other multiple myeloma drugs over the long term, argued Jan van de Winkel. In the second year of therapy, patients can take a lower dose, cutting the cost to $76,000 per year, he said. “We think $76,000 is the more relevant figure because I predict that with daratumumab patients can be treated for a very long time. So I think it’s favourably priced.”

Worries about any potential pushback from payers have not dampened Darzalex's forecasts, which have been rising since data from the pivotal phase II Sirius trial were released at Asco (Asco – A Sirius lead for daratumumab, May 30, 2015). EvaluatePharma revenue consensus sits at $1.17bn in 2020, with Morgan Stanley analysts going so far as to forecast sales of around $3bn by 2025 even if the drug is predominantly used in relapsed and refractory patients.

Genmab’s stock climbed 13% this morning, anticipating some hefty future milestones and royalties, now payable by J&J. 

Versus Empliciti

Darzalex is the first CD38-targeting MAb to get the green light from the FDA, well ahead of the other two agents in the class, Sanofi’s SAR650984 (isatuximab) and MorphoSys’s MOR202, which are still in phase II. The latter looks unlikely to progress further unless it gets a new partner – Celgene handed back rights to MorphoSys earlier this year.

Genmab’s drug has also leapfrogged Bristol-Myers Squibb/AbbVie’s elotuzumab – now brand named Empliciti – to become the first monoclonal antibody for use in multiple myeloma. Empliciti, which targets CS1, has a PDUFA data of February 29, 2016, but clearly approval could come sooner.

However, even if Empliciti does get the go-ahead in the near future, Mr van de Winkel does not seem concerned. “Empliciti has zero monotherapy efficacy – it only works well in combination with Revlimid. I think that Empliciti will find its niche, but I think it’s a very different molecule.”

Darzalex combos

But Darzalex might also end up being part of a combination, especially if it is to expand out of its current indication as a fourth-line treatment – and J&J and Genmab are already investigating this.

“We already have five phase III trials ongoing, two of them in the relapsed/refractory setting,” Mr van de Winkel said, adding that interim results and a filing in the second-line setting could come within a year. There are three trials in the front-line setting, two in transplant-ineligible and one in transplant-eligible patients.

Ongoing phase III trials of Darzalex
Setting Combination with Trial ID Primary completion date
Relapsed or refractory multiple myeloma Velcade and dexamethasone NCT02136134 Mar 2017
Relapsed or refractory multiple myeloma Revlimid and dexamethasone NCT02076009 May 2017
Transplant-ineligible participants with previously untreated multiple myeloma Velcade melphalan-prednisone   NCT02195479 May 2018
Transplant-ineligible participants with previously untreated multiple myeloma Revlimid and dexamethasone NCT02252172 Dec 2019
Transplant-eligible participants with previously untreated multiple myeloma Velcade, thalidomide and dexamethasone NCT02541383 Aug 2022

Again, Mr van de Winkel stressed that cost need not be an issue, saying that many of the drugs used in the combos, like melphalan and prednisone, are generic, while “others, like J&J's Velcade, will become generic from 2017 onwards”. Revlimid’s patent is set to expire in 2019.

However, with Darzalex having such a large price tag, the issue of cost is unlikely to go away. “J&J wants to make Darzalex the core part of a combination regimen for all types of treatment for multiple myeloma,” Mr van de Winkel concluded. “And you cannot get there if you make the individual drug too expensive.”

Time will tell whether J&J has priced Darzalex at the right level.

To contact the writer of this story email Madeleine Armstrong in London at [email protected] or follow  @medtech_ma on Twitter

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