Since the approval of IMBRUVICA (ibrutinib) in 2013, the rise of BTK inhibitors is clear. JAYPIRCA (pirtobrutinib) is the newest addition to the approved BTK inhibitor family to treat lymphoma/leukemia (mantle cell lymphoma and chronic lymphocytic leukemia).
The pharmaceutical sector is very competitive and everyone wants to find best-in-class therapy. When the first-in-class therapy is approved, everyone studies the label and tries to come up with a better version of the product. So is JAYPIRCA better than IMBRUVICA?
Indication
Ten years is a long time, but also a very short time in the pharmaceutical world. The first-in-class is only a historical title if it cannot compete with the upcoming products from the competitors. To combat the competition, the first-in-class has the best position to expand the indication.
Below are IMBRUVICA’s indications for adults:
mantle cell lymphoma (MCL) who have received at least one prior therapy
chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with or without 17p deletion
Waldenström’s macroglobulinemia (WM), a slow-growing type of non-Hodgkin lymphoma
marginal zone lymphoma (MZL) who require systemic therapy and have received at least one prior anti-CD20-based therapy.
Chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy.
Below are JAYPIRCA’s indications for adults:
relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
Comparing the two products, IMBRUVICA has mover indications and only MCL and CLL/SLL indications overlap with different conditions. Below is a summary of NCCN guideline version 1.2024 for MLC and CLL/SLL.
JAYPIRCA is a third-line therapy (the patient must fail at least two lines of therapy, including BTK inhibitor).
JAYPIRCA is the third line of therapy to treat MCL.
IMBRUVICA is one of the recommended first-line therapies to treat CLL/SLL.
IMBRUVICA with a combination of rituximab first consolidation/second-line therapy to treat MCL.
For JAYPIRCA to come into the market 10 years after IMBRUVICA and not establish guidelines to become at least a second line of therapy is very disappointing. Moreover, non-covalent BTK inhibitors like JAYPIRCA are known to cause cancer cells to be resistant to BTK inhibitors. IMBRUVICA however, covalently binds to BTK inhibitor which is not a reversible process and has a lower probability of causing resistance compared to JAYPIRCA.
As JAYPIRCA’s indications are less remarkable than IMBRUVICA’s indications, let’s look at whether JAYPIRCA can provide a better quality of life to MCL and CLL/SLL patients.
HOW EASY IS IT TO BE ON JAYPIRCA?
Below is JAYPIRCA’s dosage and administration:
available in 50 mg or 100 mg tablets.
The recommended administration is 200 mg by mouth once daily.
Dose adjustment is required in patients with renal (kidney) problems:
If severe renal impairment, reduce the dose to 100 mg once daily if on 200 mg once daily. Otherwise, reduce the dose to 50 mg once daily. If on 50 mg once daily, stop taking JAYPIRCA
No dosage adjustment is required for mild or moderate renal impairment patients.
Many drug interactions
Avoid taking JAYPIRCA with strong CYP3A4 inhibitors and strong or moderate CYP3A4 inducers. If cannot be avoided, reduce the dose.
Strong CYP3A4 inhibitors include Clarithromycin, Itraconazole, etc
Strong/moderate CYP3A4 inducers include Carbamazepine, Phenytoin, Rifampicin, etc
There are other drug interactions, but CYP3A4 is the major interaction.
Below are IMBRUVICA’s dosage and administration:
Available in 3 different dosage formulations:
Capsules: 70 mg and 140 mg
Tablets: 140 mg, 280 mg, 420 mg, and 560 mg
Oral suspension: 70 mg/mL
The recommended administrations are the following:
MCL: 560 mg taken orally once daily
CLL/SLL: 420 mg taken orally once daily
Dose adjustment is required in patients with hepatic (liver) problems:
If severe hepatic impairment (Child-Pugh Class C), avoid taking IMBRUVICA
If mild or moderate (Child-Pugh Class A and B), reduce dosage and monitor for adverse reactions.
No safety has been evaluated in patients with Child-Pugh Class A to C.
Mainly CYP3A drug interactions
Dose adjustment is recommended when taking IMBRUVICA with strong or moderate CYP3A inhibitors.
Avoid IMBRUVICA when taking strong CYP3A4 inducers.
By comparing JAYPIRCA and IMBRUVICA, JAYPIRCA is beneficial to patients with liver problems as IMBRUVICA did not evaluate safety in hepatic impaired patients. Similarly, IMBRUVICA would be beneficial in patients with kidney problems as there is no need for dosage adjustment.
The variety of formulations and dosages IMBRUVICA comes in provides less pill burden as you only require 1 tablet/day, whereas JAYPIRCA requires 2 tablets/day when dose adjustments are not required.
Unless MCL or CLL/SLL patients who failed at least two lines of therapy (including BTK inhibitor) with liver problems are a target patient population, IMBRUVICA is a much better option.
EFFICACY
JAYPIRCA
Patients with MCL Previously Treated with a BTK Inhibitor
Out of 120 patients, the overall response rate for JAYPIRCA was 50% with 13% of patients having complete response.
The median duration of response was 8.3 months
Patients with CLL/SLL Previously Treated with a BTK Inhibitor and a BCL-2 inhibitor
Out of 108 patients, the overall response rate for JAYPIRCA was 72% with 0% of patients having complete response.
The median duration of response was 12.2 months
IMBRUVICA
Patients with MCL
Out of 111 patients, the overall response rate for IMBRUVICA was 65.8% with 13% of patients having complete response.
The median duration of response was 17.5 months
Patients with CLL/SLL
Out of 195 patients, the overall response rate for IMBRUVICA was 42.6% with 0% of patients having complete response.
It is difficult to compare JAYPIRCA to IMBRUVICA in terms of efficacy due to different patients enrolled in respective clinical trials. It seems that the JAYPIRCA was developed to be a “rescue” BTK inhibitor treatment option for MCL and CLL/SLL as JAYPIRCA was not studied in BTK inhibitor treatment-naive patients.
THE COST/PRICE COMPARISON
As a pharmacist who practiced pharmacy in a retail setting, with all the benefits the medications can provide if it is not affordable, patients do not benefit from the treatment.
According to Drugs.com, IMBRUVICA will cost just short of $17,000 for 420 mg 28-count tablets. As for JAYPIRCA, it will cost a little over $23,000 for 100 mg 60-count tablets.
Given that IMBRUVICA has been out in the market for a long time, listed as one of the first-line therapies in CLL/SLL, and cheaper than JAYPIRCA, I would expect the insurance and Medicare Part D to have better coverage for IMBRUVICA compared to JAYPIRCA. However, IMBRUVICA treatment costs will go up if rituximab co-administration therapy is chosen to treat CLL/SLL.
CONCLUSION
When comparing JAYPIRCA and IMBRUVICA, IMBRUVICA seems better than JAYPIRCA in almost all situations unless MCL or CLL/SLL diagnosed patients who failed at least two lines of therapy (including BTK inhibitor) with liver problems are a target patient population.
IMBRUVICA has more indications, is listed as a first-line therapy for the treatment of MCL and CLL/SLL, and is generally cost-effective when compared to that of JAYPIRCA.
However, as studying the package label, it is perhaps unfair to compare JAYPIRCA to IMBRUVICA directly. The indication and clinical studies for JAYPIRCA seem it was not to be a first-line therapy but to provide another BTK inhibitor option in patients who failed multiple therapies including BTK inhibitor. Perhaps this strategic move was to improve the chance of getting the FDA approval by not trying to compete with available first-line therapy agents. Or perhaps, the JAYPIRCA was designed as a “rescue” BTK inhibitor in patients who already failed other treatment options including BTK inhibitor therapy.
JAYPIRCA should be considered as a “last-line” therapy in treating MCL and CLL/SLL. But, after failing multiple therapies to treat MCL and CLL/SLL, is JAYPIRCA worth it to have 50% and 72% overall response respectively for 8.3 and 12.2 months, while spending $23,000/month without insurance coverage? I do not know.
If the 50% overall response rate and 8.3 months to treat MCL and 72% overall response rate with 12.2 months to treat CLL/SLL improve quality of life, JAYPIRCA is right for you. So, when thinking of taking JAYPIRCA, please have a genuine conversation with your oncologist, primary doctor, pharmacist, and family to choose the best treatment option for you.
Thank you for your time.
-ProoSt!