• DARZALEX (dara­tu­mu­mab) approved by U.S. FDA for heavily pre-treated or double refractory multiple myeloma
• First mono­clonal anti­body approved for multiple myeloma
• Financial guidance updated to in­clude USD 45 million mile­stone pay­ment

Copenhagen, Denmark (Press Release) – Genmab A/S (OMX: GEN) announced today the U.S. Food and Drug Admin­istra­tion (FDA) has approved DARZALEX™ (dara­tu­mu­mab) injection for in­tra­venous in­fusion for the treat­ment of patients with multiple myeloma who have received at least three prior lines of ther­apy, in­­clud­ing a pro­te­a­some inhibitor (PI) and an immuno­modu­la­tory agent (IMiD), or who are double-refractory to a PI and IMiD.¹ This indi­ca­tion is approved under accelerated approval based on response rate. Continued approval for this indi­ca­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in con­firm­a­tory trials.

DARZALEX is the first human CD38 mono­clonal anti­body (mAb) approved any­where in the world and the first thera­peutic anti­body ever approved to treat multiple myeloma. The approval comes just two months after the Biologics License Application (BLA) was accepted for Priority Review by the FDA in September 2015. In May 2013, DARZALEX received Break­through Therapy Desig­na­tion from the FDA for the indi­ca­tion approved today. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive world­wide license to develop, manu­fac­ture and com­mer­cial­ize DARZALEX.

Genmab will receive a mile­stone pay­ment from Janssen of USD 45 million asso­ci­ated with the first com­mer­cial sale of the prod­uct in the United States. As this is ex­pec­ted to occur quickly after this approval, Genmab is im­prov­ing its financial guidance for the year. See the Outlook section of this announcement for more in­­for­ma­tion.

“This is an im­por­tant day for patients in the United States with double refractory multiple myeloma, who will now have DARZALEX as a new treat­ment option for this incurable disease. The suc­cess­ful approval of DARZALEX is the culmination of many years of hard work, perseverance and col­lab­o­ra­tion on the part of clin­i­cal study investigators, Genmab employees and our colleagues at Janssen. Our work at Genmab is aimed at im­prov­ing the lives of patients and we are both proud and humbled to have created this first-in-class thera­peutic anti­body and to have played a key part in the rapid and expansive devel­op­ment of DARZALEX,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The pivotal Phase II MMY2002 (SIRIUS) study showed treat­ment with single-agent DARZALEX resulted in an over­all response rate (ORR) of 29.2 per­cent in patients who received a median of five prior lines of ther­apy, in­­clud­ing a PI and an IMiD, and is ex­pec­ted to be published in a top medical journal soon. Stringent com­plete response (sCR) was reported in 2.8 per­cent of patients, very good partial response (VGPR) was reported in 9.4 per­cent of patients, and partial response (PR) was reported in 17 per­cent of patients. For responders, the median duration of response was 7.4 months. At base­line, 97 per­cent of patients were refractory to their last line of ther­apy, 95 per­cent were refractory to both a PI and an IMiD, and 77 per­cent were refractory to alkylating agents. Sixty-three per­cent were refractory to poma­lido­mide, and 50 per­cent were refractory to car­filz­o­mib.1 Additional data from four other studies, in­­clud­ing the Phase I/II GEN501 mono­therapy study – published in The New England Journal of Medicine in August 2015 – also sup­port this approval.

The warnings and precautions for DARZALEX in­clude in­fusion-related reac­tions (IRRs) and inter­fer­ence with serological testing.² The most commonly occurring adverse reac­tions (in 20 per­cent or more of patients in three pooled clin­i­cal studies) were IRRs, fatigue, nausea, back pain, anemia, neu­tro­penia (abnormally low levels of neu­tro­phils, a type of white blood cell) and thrombo­cytopenia (abnormally low levels of platelets in the blood).¹

In data from three pooled clin­i­cal studies in­­clud­ing a total of 156 patients, four per­cent of patients dis­con­tinued treat­ment due to adverse reac­tions, none of which were con­sidered drug-related. IRRs were reported in approx­i­mately half of all patients treated with DARZALEX, the majority of which (91 per­cent) occurred during the first in­fusion. Seven per­cent of patients had an IRR at more than one in­fusion. Common (≥5 per­cent) symp­toms of IRRs in­cluded nasal congestion, chills, cough, allergic rhinitis, throat irritation, dyspnea, and nausea, and these were mild to mod­er­ate in severity.1 Severe IRRs (4 per­cent), in­­clud­ing bron­cho­spasm (1.3 per­cent), hyper­tension (1.3 per­cent), and hypoxia, or de­creased oxygen supply to the tissues (0.6 per­cent), were also reported.¹

The rec­om­mended dose of DARZALEX is 16 mg/kg body weight admin­istered as an in­tra­venous in­fusion.¹ The dosing schedule begins with weekly admin­istra­tion (weeks 1 to 8), and reduces in frequency to every two weeks (weeks 9-24) and ultimately every four weeks (week 25 onwards until disease pro­gres­sion).¹

Janssen is cur­rently the global sponsor of all but one clin­i­cal study, the Phase I/II GEN501 mono­therapy study which was conducted by Genmab. DARZALEX will be com­mer­cial­ized in the U.S. by Janssen Biotech, Inc.

OUTLOOK

 
Genmab is im­prov­ing its 2015 financial guidance published on November 3, 2015, due to the inclusion of a dara­tu­mu­mab mile­stone of USD 45 million asso­ci­ated with the antic­i­pated first commercial sale of the prod­uct in the United States, fol­low­ing the FDA approval of dara­tu­mu­mab.

Operating Result

We ex­pec­t our 2015 revenue to be in the range of DKK 1,025 – 1,100 million, an in­­crease of DKK 300 million com­pared to DKK 725 – 800 million in the pre­vi­ous guidance. We have in­­creased our pro­jected dara­tu­mu­mab mile­stones to DKK 540 – 600 million from the prior esti­mate of DKK 240 – 300 million due to inclusion of an addi­tional mile­stone of USD 45 million asso­ci­ated with the first commercial sale of the prod­uct in the United States. Our pro­jected revenue for 2015 consists primarily of non-cash amortization of deferred revenue totaling DKK 285 million, dara­tu­mu­mab & DuoBody® mile­stones and royalties on sales of Arzerra® of DKK 80 million.

We ex­pec­t our 2015 operating expenses to remain in the range of DKK 550 – 600 million.

The transfer of the ofatumumab col­lab­o­ra­tion from GSK to Novartis became effective in March 2015. This results in Genmab having no ofatumumab devel­op­ment costs in 2015 and beyond, and no require­ment to pay its deferred funding liability totaling DKK 176 million. During the first quarter of 2015, the deferred liability was reversed and the corresponding gain was recog­nized as other income in our income state­ment.

As a result of the in­­creased revenue, we now ex­pec­t the operating income for 2015 to be approx­i­mately DKK 625 - 700 million, com­pared to DKK 325 - 400 million in the pre­vi­ous guidance.

Cash Position

There is no change to the cash position at the end of 2015 of DKK 3,000 - 3,100 million as we ex­pec­t to receive pay­ment for the addi­tional mile­stone shortly after year-end. The revised guidance in­cludes proceeds from warrants exercised in 2015.

In addi­tion to factors already mentioned, the esti­mates above are subject to change due to numerous reasons, in­cluding but not limited to achieve­ment of certain mile­stones asso­ci­ated with our col­lab­o­ra­tion agree­ments; the timing and variation of devel­op­ment activities (including activities carried out by our col­lab­o­ra­tion partners) and related income and costs; Arzerra sales and corresponding royalties to Genmab; fluctuations in the value of our mar­ketable se­cu­ri­ties; and currency exchange rates. The financial guidance does not in­clude any addi­tional poten­tial proceeds from future warrant exercises and also assumes that no addi­tional sig­nif­i­cant agree­ments are entered into during 2015 that could ma­teri­ally affect the results.

About multiple myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is char­ac­ter­ized by an excess proliferation of plasma cells.³ Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lym­phoma.⁴ Approximately 26,850 new patients will be diag­nosed with multiple myeloma and approx­i­mately 11,240 people will die from the disease in the U.S. in 2015.⁵ Globally, it is esti­mated that 124,225 people will be diag­nosed and 87,084 will die from the disease in 2015.⁶ While some patients with multiple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms which can in­clude bone problems, low blood counts, cal­cium elevation, kidney problems or in­fec­tions.⁷ Patients who relapse after treat­ment with standard ther­a­pies, in­­clud­ing PIs or IMiDs, have poor prognoses and few treat­ment options.⁸

About DARZALEX™ (dara­tu­mu­mab)

DARZALEX™ (dara­tu­mu­mab) injection for in­tra­venous in­fusion is indicated in the United States for the treat­ment of patients with multiple myeloma who have received at least three prior lines of ther­apy, in­­clud­ing a pro­te­a­some inhibitor (PI) and an immuno­modu­la­tory agent (IMiD), or who are double-refractory to a PI and IMiD.1 DARZALEX is the first mono­clonal anti­body (mAb) to receive U.S. Food and Drug Admin­istra­tion (FDA) approval to treat multiple myeloma. For more in­­for­ma­tion, visit www.DARZALEX.com.

Daratumumab is a human IgG1k mono­clonal anti­body (mAb) that binds with high affinity to the CD38 molecule, which is highly ex­pressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through pro­grammed cell death, or apop­tosis,^1,9 and multiple immune-mediated mecha­nisms, in­­clud­ing complement-dependent cyto­tox­icity,^1,9 anti­body-dependent cellular phago­cytosis^10,11 and anti­body-dependent cellular cyto­tox­icity.^1,9

Five Phase III clin­i­cal studies with Dara­tu­mu­mab in re­lapsed and frontline settings are cur­rently ongoing, and addi­tional studies are ongoing or planned to assess its poten­tial in other malignant and pre-malignant diseases on which CD38 is ex­pressed, such as smol­der­ing myeloma and non-Hodgkin’s lym­phoma.

Access to DARZALEX

DARZALEX will be avail­able for distribution in the U.S. within two weeks fol­low­ing FDA approval. Janssen Biotech offers com­pre­hen­sive access and sup­port in­­for­ma­tion, resources and services to assist U.S. patients in gaining access to DARZALEX through the Janssen CarePath pro­gram. For more in­­for­ma­tion, health care providers or patients can contact: 1-844-55DARZA (1-844-553-2792). Information will also be avail­able at www.DARZALEX.com.

Important Safety Information

CONTRAINDICATIONS - None

WARNINGS AND PRECAUTIONS

Infusion Reactions - DARZALEX can cause severe in­fusion reac­tions. Approximately half of all patients ex­peri­enced a reac­tion, most during the first in­fusion. Infusion reac­tions can also occur with sub­se­quent in­fusions. Nearly all reac­tions occurred during in­fusion or within 4 hours of com­plet­ing DARZALEX. Prior to the in­tro­duc­tion of post-infusion medication in clin­i­cal trials, in­fusion reac­tions occurred up to 48 hours after in­fusion. Severe reac­tions have occurred, in­­clud­ing bron­cho­spasm, hypoxia, dyspnea, and hyper­tension. Signs and symp­toms may in­clude res­pira­tory symp­toms, such as cough, wheezing, larynx and throat tightness and irritation, laryngeal edema, pul­mo­nary edema, nasal congestion, and allergic rhinitis. Less common symp­toms were hypo­­tension, headache, rash, urticaria, pruritus, nausea, vomiting, and chills.

Pre-medicate patients with antihistamines, anti­pyretics and corticosteroids. Frequently monitor patients during the entire in­fusion. Interrupt DARZALEX in­fusion for reac­tions of any severity and institute medical man­agement as needed. Permanently dis­con­tinue DARZALEX ther­apy for life-threatening (Grade 4) reac­tions. For patients with Grade 1, 2, or 3 reac­tions, reduce the in­fusion rate when re-starting the in­fusion.

To reduce the risk of delayed in­fusion reac­tions, admin­ister oral corticosteroids to all patients the first and second day after all in­fusions. Patients with a history of obstructive pul­mo­nary disorders may require addi­tional post-infusion medications to man­age res­pira­tory com­pli­ca­tions. Consider pre­scrib­ing short- and long-acting bron­cho­di­lators and inhaled corticosteroids for patients with obstructive pul­mo­nary disorders.

Interference with Serological Testing - Dara­tu­mu­mab binds to CD38 on red blood cells (RBCs) and may result in a pos­i­tive Indirect Antiglobulin Test (Coombs test). Dara­tu­mu­mab-mediated pos­i­tive indirect anti­globulin test may persist for up to 6 months after the last dara­tu­mu­mab in­fusion. Dara­tu­mu­mab bound to RBCs may mask detection of anti­bodies to minor an­ti­gens in the patient’s serum1. The deter­mi­na­tion of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this inter­fer­ence with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Interference with Determination of Complete Response - Dara­tu­mu­mab is a human IgG kappa mono­clonal anti­body that can be detected on both, the serum protein electrophoresis (SPE) and immuno­fixa­tion (IFE) assays used for the clin­i­cal monitoring of endogenous M-protein. This inter­fer­ence can impact the deter­mi­na­tion of com­plete response and of disease pro­gres­sion in some patients with IgG kappa myeloma protein.

Adverse Reactions - The most frequently reported adverse reac­tions (incidence ≥20%) were: in­fusion reac­tions, fatigue, nausea, back pain, pyrexia, cough, and upper res­pira­tory tract in­fec­tion.

DRUG INTERACTIONS - No drug inter­action studies have been per­formed.

About Genmab

Genmab is a publicly traded, inter­na­tional bio­technology com­pany specializing in the creation and devel­op­ment of dif­fer­en­ti­ated anti­body thera­peutics for the treat­ment of cancer. Founded in 1999, the com­pany has two approved anti­bodies, Arzerra® (ofatumumab) for the treat­ment of certain chronic lym­pho­cytic leukemia indi­ca­tions and DARZALEX™ (dara­tu­mu­mab) for the treat­ment of heavily pre­treated or double refractory multiple myeloma. Dara­tu­mu­mab is in clin­i­cal devel­op­ment for addi­tional multiple myeloma indi­ca­tions and for non-Hodgkin’s lym­phoma. Genmab also has a broad clin­i­cal and pre-clinical prod­uct pipe­line. Genmab's tech­nology base consists of val­i­dated and pro­pri­e­tary next generation anti­body tech­nolo­gies - the DuoBody® plat­form for generation of bispecific anti­bodies, and the HexaBody® plat­form which creates effector function en­hanced anti­bodies. The com­pany in­tends to leverage these tech­nolo­gies to create oppor­tu­ni­ties for full or co-ownership of future prod­ucts. Genmab has alliances with top tier pharma­ceu­tical and bio­technology com­pa­nies. For more in­­for­ma­tion visit www.genmab.com.

This Company Announcement con­tains for­ward looking state­ments. The words “believe”, “expect”, “anticipate”, “intend” and “plan” and similar ex­pres­sions identify for­ward looking state­ments. Actual results or per­for­mance may differ ma­teri­ally from any future results or per­for­mance ex­pressed or implied by such state­ments. The im­por­tant factors that could cause our actual results or per­for­mance to differ ma­teri­ally in­clude, among others, risks asso­ci­ated with pre-clinical and clin­i­cal devel­op­ment of prod­ucts, un­cer­tain­ties related to the out­come and conduct of clin­i­cal trials in­­clud­ing un­fore­seen safety issues, un­cer­tain­ties related to prod­uct manu­fac­tur­ing, the lack of mar­ket acceptance of our prod­ucts, our in­abil­ity to man­age growth, the competitive en­viron­ment in rela­tion­ to our business area and mar­kets, our in­abil­ity to attract and retain suitably qualified per­son­nel, the un­en­force­ability or lack of protection of our patents and pro­pri­e­tary rights, our rela­tion­ships with affiliated entities, changes and devel­op­ments in tech­nology which may render our prod­ucts obsolete, and other factors. For a further discussion of these risks, please refer to the risk man­agement sections in Genmab’s most recent financial reports, which are avail­able on www.genmab.com. Genmab does not under­take any obli­ga­tion to update or revise for­ward looking state­ments in this Company Announcement nor to con­firm such state­ments in rela­tion­ to actual results, unless required by law.

Genmab A/S and its sub­sid­i­aries own the fol­low­ing trademarks: Genmab®; the Y-shaped Genmab logo®; Genmab in com­bi­na­tion with the Y-shaped Genmab logo™; the DuoBody logo®; the HexaBody logo™; HuMax®; HuMax-CD20®; DuoBody®; HexaBody® and UniBody®. Arzerra® is a trademark of Novartis AG or its affiliates. DARZALEX™ is a trademark of Janssen Biotech, Inc.

References

1. PRESCRIBING INFORMATION
2. Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
3. American Cancer Society. "Multiple Myeloma Overview." Available at http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed August 2015.
4. National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed September 2015.
5. American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed September 2015.
6. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of New Cancers in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Execute. Accessed September 2015.
7. American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed August 2015.
8. Janssen JH, et al. Blood. 2012; 120.2974.
9. Michel de Weers et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. February 1, 2011. Vol. 186, No. 3 1840-1848.
10. Overdijk et al. Phagocytosis Is A Mechanism of Action for Daratumumab. Available at https://ash.confex.com/ash/2012/webprogram/Paper51257.html. Accessed September 2015.
11. Yulian Khagi and Tomer M Mark. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095–1100.

Source: Genmab