Ofatumumab to Be Available Through a Patient Access Program for CLL

Patients with chronic lymphocytic leukemia (CLL) who are being treated with ofatumumab (Arzerra) will soon have to get their therapy through an oncology patient access program, as Novartis, the manufacturer, will no longer be selling the drug commercially for this indication.¹

This program will be facilitated through the Patient Access Novartis Oncology, and a company spokesperson said they will be working with prescribing oncologists and specialty pharmacists on a transition plan. No timeline for the transition has been announced.

The patient access program will provide treatment at no cost to patients, but oncologists will have to request a prescription for their patients with CLL, which will then be made available by a dispensing pharmacy, the spokesperson told OncLive. Until the access program launches, ofatumumab will continue to be made commercially available through existing prescription processes.

The access program is being created, according to the Novartis spokesperson, to prevent any increase in the payer and out-of-pocket cost of ofatumumab that could result from the introduction of the agent for multiple sclerosis under the brand name Kesimpta, which had been approved by the FDA in August 2020 in a subcutaneous formulation that patients can administer at home once monthly via an autoinjector pen.^2,3

Richard R. Furman, MD, director of the CLL Research Center, professor of medicine, division of Hematology/Oncology at Weill Cornell Medical College, New York, New York, pointed out that ofatumumab is not often prescribed for CLL.

“It’s a situation where it never was all that efficacious [in this disease]. The agent has a very short response rate and it never really got a lot of use,” Furman told OncLive. “It was approved based on data that many physicians didn’t think was all that exciting.”

Furman added that a similar situation occurred with another CLL therapy: alemtuzumab (CamPath), which received regulatory approval for CLL in 20014 and was also subsequently repurposed as a therapy for multiple sclerosis under the trade name Lemtrada in 2014.⁵

“Alemtuzumab couldn’t be marketed successfully for both (indications) and since the use in CLL was so infrequent, Genzyme decided to make the CLL indication an expanded use program and only bill for the use [in multiple sclerosis],” Furman explained. The ofatumumab access program is likely to be similar to that of alemtuzumab, according to Furman, with minimal paperwork.

Obinutuzumab (Gazyva)⁶ and rituximab (Rituxan)⁷ are more frequently prescribed for CLL, according to Furman, and 2 biosimilars are currently available for rituximab: rituximab-pvvr (Ruxience)⁸ and rituximab-abbs (Truxima).⁹

In January 2018, Novartis transitioned ofatumumab to patient access programs outside of the United States. Approximately 600 to 700 patients in the United States are being prescribed ofatumumab, according to the Novartis spokesperson.

Furman currently has several patients using ofatumumab, but these are patients with Waldenström macroglobulinemia, not CLL. Ofatumumab is a human monoclonal antibody that is designed to target the CD20 molecule found on the surface of normal B lymphocytes and on B cell malignancies. “We thought for a disease like Waldenström macroglobulinemia, which has low CD20 expression, the higher dosing of ofatumumab and the use of complement might actually improve efficacy,” Furman explained.

To this end, Furman and his colleagues conducted a study which explored ofatumumab in patients with Waldenström macroglobulinemia.¹⁰ A total of 37 patients were included in the safety and efficacy analyses. Participants received ofatumumab for 5 weeks for up to 3 treatment cycles. Patients were randomized to 2 groups with different dosing schedules. In the study, 19 patients (51%; 95% CI, 34.4-68.1) achieved an overall response after cycle 1. Moreover, 22 patients (59%; 95% CI, 42.1-75.2) achieved an overall response following the redosing cycle. Fifteen patients (41%) achieved partial responses to treatment and 7 patients (19%) experienced minor responses.

Investigators also noted a low incidence of immunoglobulin M (Igm) flares in patients treated with ofatumumab. Surges of IgM are known to occur in patients with Waldenström macroglobulinemia who are treated with rituximab.¹¹

Novartis obtained rights for ofatumumab from Genmab in all indications in December 2015. Because of this move to discontinue sales of ofatumumab, Novartis will pay Genmab a lump sum of $30 million as payment for lost potential royalties.

References

1. Genmab announces plan to transition Arzerra (ofatumumab) to an Oncology Access Program for chronic lymphocytic leukemia patients in the US. News release. Genmab. August 20, 2020. Accessed September 3, 2020. bit.ly/2EYduKS.
2. Kesimpta. Prescribing information. Novartis; August 20, 2020. Accessed September 3, 2020. bit.ly/3jNzHu3.
3. FDA approves Novartis Kesimpta (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis. News release. Novartis. August 20, 2020. Accessed September 3, 2020. bit.ly/352p82h.
4. CamPath. Prescribing information. Genzyme; May 2001. Accessed September 3, 2020. bit.ly/2Gt3lqk.
5. Lemtrada. Prescribing information. Sanofi Genzyme; revised May 2020. Accessed September 3, 2020. bit.ly/353FxDu.
6. Gazyva. Prescribing information. Genentech; revised March 2020. Accessed September 3, 2020. bit.ly/352p82h.
7. Rituxan. Prescribing information. Genentech; revised March 2020. Accessed September 3, 2020. bit.ly/2Z6pqS5.
8. Ruxience. Prescribing information. Pfizer; revised May 2020. Accessed September 3, 2020. bit.ly/2QRDslZ.
9. Truxima. Prescribing information. Celltrion; revised May 2020. Accessed September 3, 2020. https://bit.ly/32PqIBW.
10. Furman RR, Eradat HA, DiRienzo CG, et al. Once weekly ofatumumab in untreated or relapsed Waldenstrom’s macroglobulinaemia: an open-label, single-arm phase 2 study. Lancet Haematol. 2017; 4:e24-34. doi.org/10.1016/S2352-3026(16)30166-1
11. Ghobrial IM, Fonseca R, Greipp PR, et al. Initial immunoglobin M ‘flare’ after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemia: an Easter Cooperative Oncology Group study. Cancer.2004;101(11):2593-8. doi:10.1002/cncr.20658.