The reimbursement experience with AbbVie’s Orilissa (elagolix) in endometriosis-related pain is likely to spill over to Myovant Sciences’ relugolix, and both drugs’ use to control menstrual bleeding in uterine fibroids, if approved.

To prescribe Orilissa beyond the specified limit on its label, a physician letter stating the need and the drug’s effectiveness is sometimes required.

While physicians expected access after such a process, it was not a uniform experience for all doctors.

One analyst noted that insurance coverage is a major obstacle for Orilissa’s adoption. AbbVie stated that approximately 70 per cent of patients taking Orilissa have access to the drug through their insurance plans, and the rest are offered the drug for free.

The challenge of proving adequate evidence for the reimbursement of prolonged gonadotropin-releasing hormone (GnRH) antagonist treatments like Orilissa and relugolix will likely extend to other indications like uterine fibroids.

Since treatment is driven by patients this may be even more obvious, especially as endometriosis-related symptoms are more distressing than those in uterine fibroids.

AbbVie plans to file a New Drug Application (NDA) for Orilissa to address menstrual bleeding with uterine fibroids in mid-2019 based on top line data from two trials, it was announced in November 2018.

Myovant announced data from one trial in May and plans an NDA in 4Q pending positive results from a second Phase III trial.

ObsEva has a further Phase III GnRH antagonist, linzagolix, with results expected in mid-2019.

As a likely third-to-market asset, the impact of ObsEva’s efforts to differentiate linzagolix from Orilissa and relugolix by offering dosing flexibility remains unclear.

Individual analysts estimated revenues for Orilissa, relugolix and linzagolix for endometriosis-related pain to be US $1.58bn in 2027, $1bn in 2028 and $992.6m in 2028, respectively.

Sales for their use to address bleeding with uterine fibroids are anticipated to be $985m in 2027, $700m in 2028 and $600m in 2028, respectively.

The market caps for AbbVie, Myovant and ObsEva are $107.83bn, $785m and $489m, respectively. Orilissa was approved for endometriosis-related pain in June 2018 and launched at a list price of $10,000 per year.

AbbVie and Myovant did not respond to a request for comment.

Orilissa experience across women’s health

Chief Medical Director of Managed Markets, Dr Richard Stefanacci, said that initial reimbursement challenges with Orilissa use for endometriosis-related pain will likely carry over to Orilissa’s and relugolix’s use in patients with uterine fibroids.

R. Brett McQueen, assistant professor at the Center for Pharmaceutical Outcomes Research, University of Colorado said that since long-term evidence is lacking in women’s health, these drugs will likely face the same issues with payers requiring additional information to cover using the drugs for longer than what is noted on their labels.

It is quite common to consider prescribing Orilissa beyond the time period approved, given the lack of new and effective treatment options.

Orilissa is indicated at either 150mg once daily for two years or 200mg twice-daily for up to six months. The relugolix Phase III program is testing the drug for six months of use.

Stefanacci added that in both uterine fibroids and endometriosis, the need for therapy is dictated by the patient, unlike in blood pressure medications where test data drives treatment.

Dr Charles Ascher-Walsh, director of Gynaecology and Urogynaecology at Mount Sinai School of Medicine said that it will be surprising if the drugs are very successful in treating bleeding associated with uterine fibroids where symptoms are not as debilitating as those in endometriosis, since symptomatically women deal better with fibroids than endometriosis.

Moreover, the side-effect trade off is clearer for endometriosis compared to uterine fibroids, he noted.

However, Dr Tatiana Burnett, consultant at the Department of Obstetrics and Gynaecology, Mayo Clinic, disagreed about whether women are more likely to seek care for endometriosis-related pain as opposed to heavy menstrual bleeding related to fibroids.

Even women with endometriosis have an average eight-year delay from symptoms to diagnosis, some of which is due to the normalisation of symptoms either by family, friends or physicians, she added.

McQueen noted that the prevalence of endometriosis is probably underestimated given its poor diagnosis history, so as more drugs become available, it could have a major impact on healthcare budgets.

Gynaecologists are familiar with identifying symptoms, but drug approvals and advertisements may result in more patients speaking out about their symptoms.

Payer pushback

Burnett and Ascher-Walsh said that the reimbursement experience for Orilissa in endometriosis-related pain, including the need for prior authorisation or outcomes-based contracts, has been variable depending on an individual patient’s insurance.

While she has not been denied coverage for her patients, Burnett noted she has heard about rejections from her colleagues.

Ascher-Walsh said that based on his experience, although it is not straightforward, insurance companies can be convinced to pay for Orilissa with a letter from the physician.

Stefanacci agreed that in general, physicians will need to write an appeal based on the literature to support continued use, and the vast majority of written appeals are successful.

A member of the ICER report group, McQueen said that based on its approved label, Orilissa is under the cost-effectiveness threshold the Institute for Clinical and Economic Review (ICER) used in its analysis.

However, during the ICER panel, gynaecologists said they would continue treatment for longer periods of time if it worked, and that is where the cost-effectiveness estimate dropped.

The ICER is an independent organisation that objectively evaluates the clinical and economic value of prescription drugs, medical tests, and other health care and health care delivery innovations, according to its website.

A health economist at Medicus Economics, Scott Johnson, said that an AbbVie-sponsored analysis looked at Orilissa treatment for up to two years and found it to be cost effective.

The analysis compared Orilissa to Lupron (leuprolide acetate) instead of placebo, as done by ICER. Lupron is indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions.

According to Johnson, the AbbVie analysis indicated that if a plan covers Lupron, it should also cover Orilissa.

US payers are increasingly using cost-effectiveness analyses, which are partly driven by the need for value-based plan designs.

McQueen said that payers may explore outcomes-based contracts to allow continued access to the drug if effective. Such contracts would involve financial rebates where the manufacturer is required to pay back the cost of the drug if the patient does not respond.

Nonetheless, long-term use also comes with safety questions like the higher risk of bone mineral density loss. The one to two year time period used to determine cost effectiveness may be inadequate to capture any adverse event changes.

While Orilissa is currently the only approved GnRH antagonist, relugolix is in two Phase III studies for patients with endometriosis-related pain, with completion dates in December.

McQueen noted that as more drugs get approved for endometriosis-related pain, companies may provide additional rebates to retain a drug’s position on a formulary tier, but list prices would be unlikely to change.

Stefanacci said that factors like bone loss leading to fractures would be a consideration for providers and payers alike, but any differentiation between multiple drugs on that front will have to be significant, and it will not be substantial if it is a class effect or based on just one trial.

by Manasi Vaisya in New York

Manasi Vaidya is a Senior Reporter for Pharmaceutical Technology parent company GlobalData’s investigative journalism team. A version of this article originally appeared on the Insights module of GlobalData’s Pharmaceutical Intelligence Centre. To access more articles like this, visit GlobalData.