With Oxlumo FDA OK, Alnylam Unveils Value-Based Program

With its third FDA approval in less than two-and-a-half years, Alnylam Pharmaceuticals, Inc. is bringing another orphan drug for a rare condition to the U.S. market. And similar to the first two, Oxlumo (lumasiran) comes with a costly price tag. To help provide payers with some predictability around costs, the company is extending a new value-based agreement, as well as offering another VBA that the company introduced with its previous approval.

On Nov. 23, the FDA approved Alnylam’s Oxlumo for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary oxalate levels in pediatric and adult patients. The agency says it is the first treatment approved for the rare genetic disorder, in which the body overproduces oxalate. This, in turn, results in the deposition of calcium oxalate in the kidneys and urinary tract, which can lead to kidney stones, nephrocalcinosis, kidney failure and organ damage throughout the body.

It is the third RNA interference (RNAi) therapeutic the FDA has OK’d following Alnylam’s Givlaari (givosiran), approved Nov. 20, 2019, to treat adults with acute hepatic porphyria (SMA 12/16/19, p. 1), and its Onpattro (patisiran), approved Aug. 10, 2018, for the treatment of adults with polyneuropathy caused by hereditary transthyretin-mediated (hATTR) amyloidosis (SMA 9/18, p. 11). Oxlumo is also the first RNAi therapeutic approved for use in both adult and pediatric populations.

During a Nov. 24 conference call to discuss the approval, John Maraganore, Ph.D., CEO, pointed out that Oxlumo was approved just ahead of its Dec. 3 FDA action date.

In PH1, Maraganore noted, there were previously no approved treatments for this “life-threatening condition.…Until now, the only intervention that could alleviate the profound oxalate burden for these patients was a dual liver/kidney transplant.”

Initial onset is usually in the pediatric population, but patients can present with symptoms at any age, said Akshay Vaishnaw, M.D., Ph.D., president of R&D, during the call. “PH1 poses a tremendous physical, emotional and economic burden on patients and families impacted by the disease.” It is an “inexorably progressive disease” that has an “unpredictable rate of disease progression.…Unfortunately a significant proportion of patients present with kidney failure,” and the condition ultimately leads to end-stage renal disease (ESRD).

‘Dialysis Is Inadequate’

“Once kidney function has been fully compromised, dialysis is the only means to remove the excess oxalate from the body, but even with an intensive regimen of several hours a day and upwards of six sessions a week, dialysis is inadequate in removing all of the oxalate that the liver continues to produce,” explained Vaishnaw. “This leads to systemic oxalosis, with oxalate depositing and accumulating” in other tissues, including “the eyes, heart, bones and joints.” And complications from ESRD and a transplant “are associated with high morbidity and mortality.”

According to Andy Orth, senior vice president and head of U.S. business, “we estimate the total genetic prevalence of PH1 to be in the range of four individuals per million in the U.S. and Europe, with up to 2,100 patients who may have a confirmed PH1 diagnosis. We believe a segment of that population, constituting approximately 1,000 to 1,700 patients in the U.S. and EU, would include patients who are diagnosed but not transplanted and, thus, eligible to receive Oxlumo. We expect the initial commercial uptake to be primarily among diagnosed pediatric patients, where there is more urgency to treat, and expect robust penetration in the remaining untransplanted patients with active and diagnosed disease over time.”

As with the company’s first two approvals, Oxlumo is expensive. “In the U.S., the average price for Oxlumo before mandatory discounts to government programs is estimated to be about $490,000 per patient per year. This is based on patient need, demonstrated” through clinical trials for the drug, said Orth during the call. “In a real-world setting, since Oxlumo is indicated for both pediatric and adult patients, actual costs will vary relative to patient use and weight. We believe the average effective net price for Oxlumo will be about $380,000 when taking into account expected discounts to government insurers and programs such as Medicaid.”

Orth said that multiple considerations went into the company’s determination of Oxlumo’s price:

• PH1 is a “debilitating disease” that usually presents in childhood.
• It comes with the risk of renal failure and transplant.
• It has an ultra-rare patient population.
• Oxlumo is the first therapy to treat PH1.
• Alnylam is offering VBAs to reduce access barriers.

With Onpattro and Givlaari, Alnylam has had plenty of experience with launching drugs for ultra-rare patient populations. “With the global launch plans, we will leverage much of the commercial infrastructure that’s already been built for Onpattro and Givlaari,” said Maraganore.

Orth noted that Alnylam has “executed approximately 30 VBAs” for Onpattro and Givlaari. For Oxlumo, the company says it is “in active discussions with leading payers and has reached an agreement in principle with Express Scripts, Harvard Pilgrim, and Highmark to pursue VBAs.”

Alnylam is offering a new VBA component for Oxlumo: a patient need adjustment (PNA) program. The agreement, said Orth, will “ensure seamless access to therapy for patients and budget predictability for payers.” Because the drug is indicated for both pediatric and adult patients, and dosing is based on body weight, “individual needs…will vary and may change over time. To address uncertainty with regard to cost predictability, a participating payer will qualify for a PNA rebate if the average number of vials utilized by a plan member exceeds an established threshold.” During the Q&A, Orth said the company is not releasing any specifics on the vial threshold.

In addition, he explained, the company is offering its prevalence-based adjustment component that it first introduced for Givlaari. “There are often uncertainties in diagnosis rates and disease prevalence estimates in ultra-rare, poorly diagnosed orphan diseases, making it challenging for payers to predict the number of patients who will be covered within their plans. This PBA feature triggers a rebate to participating payers if the number of diagnosed patients they cover exceeds current epidemiological estimates for PH1.”

Alnylam Worked With Payers on VBAs

Maraganore said that the company developed the new VBA “in consultation with some members of the payer community. We think it really helps address budget certainty for the payer community, and I expect it to be very well-received by the payer community.”

“With the VBAs, we engage in a dialogue with the payer, and it’s highly data-driven,” elaborated Orth. “Some of the data is clearly ours from the clinical trial, how much product the individual patient is consuming, at various sizes and at various times, etc., as well as epidemiological data we find in academic research. So we bring that to the table and then go back and forth with the payer. So there are differing numbers between different diseases clearly on that front, and each one is a bit bespoke, but we don’t release the specific numbers.”

Maraganore also explained that when payers enter into one of these VBAs, Alnylam requires “certain commitments from the payers, in turn, to reimburse the product per the label, to not put in place any step edits and so forth, so it really is a give-and-take arrangement that has been very successful in our other two brands.”

Although Oxlumo’s approval came a little more than a week before its action date, Orth stated that “nevertheless, we expect to have Oxlumo available for shipment to health care providers in the U.S. by the end of” 2020. As the drug launches during the COVID-19 pandemic, “disease awareness is being driven by digital and in-person education,” he explained, adding that the team has “many, many decades of experience.”

The company is showing no signs of slowing down its drug development process. During the call, Maraganore said that the company has three additional therapies that it’s hoping to launch over the next 18 months. It was expecting a decision on the hyper-
cholesterolemia drug Leqvio (inclisiran), which will be commercialized by Novartis Pharmaceuticals Corp., by the end of the year, but Novartis said on Dec. 18 that the FDA had issued a complete response letter regarding the new drug application “due to unresolved facility inspection-related conditions.” In addition, verdicts on ATTR amyloidosis therapy vutrisiran and hemophilia treatment fitusiran are anticipated in 2021-2022.

Access the conference call recording and slides at http://investors.alnylam.com/events.

This story was reprinted from AIS Health’s monthly publication RADAR on Specialty Pharmacy. Visit https://aishealth.com/product/specialty-pharmacy.

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