Radar on Specialty Pharmacy

FDA Approved Two PARP Inhibitors for Prostate Cancer

August 11, 2020

Although poly ADP-ribose polymerase (PARP) inhibitors are not new to the market, two of them recently gained approval for use in prostate cancer for the first time. The therapies will bring a new option for the treatment of certain subpopulations of patients.

On May 19, the FDA expanded the label of AstraZeneca and Merck & Co., Inc.’s Lynparza (olaparib) to include the treatment of people with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer who have progressed following treatment with Xtandi (enzalutamide) or Zytiga/Yonsa (abiraterone acetate).

By Angela Maas

Although poly ADP-ribose polymerase (PARP) inhibitors are not new to the market, two of them recently gained approval for use in prostate cancer for the first time. The therapies will bring a new option for the treatment of certain subpopulations of patients.

On May 19, the FDA expanded the label of AstraZeneca and Merck & Co., Inc.’s Lynparza (olaparib) to include the treatment of people with deleterious or suspected deleterious germline or somatic homologous recombination repair gene-mutated metastatic castration-resistant prostate cancer who have progressed following treatment with Xtandi (enzalutamide) or Zytiga/Yonsa (abiraterone acetate).

On May 15, the FDA gave accelerated approval to Clovis Oncology, Inc.’s Rubraca (rucaparib) for the treatment of adults with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer who have been treated with androgen receptor-directed therapy and a taxane-based chemotherapy.

Two other PARP inhibitors — GSK’s Tesaro, Inc.’s Zejula (niraparib) and Pfizer Inc.’s Talzenna (talazoparib) — are on the market, and both are in clinical trials for prostate cancer.

Lynparza’s and Rubraca’s approvals are “indicative of the growing knowledge we are gaining with respect to the intermediary pathways within the cells regulating DNA repair as it relates to tumor growth,” says Winston Wong, Pharm.D., president of W-Squared Group.

The PARP inhibitors will impact “refractory patients who have failed standard-of-care therapies,” notes Mesfin Tegenu, R.Ph., president of PerformRx, LLC. First-line treatment will be with antiandrogens or taxanes, he explains: Zytiga, Yonsa, Jevtana (cabazitaxel), Taxotere (docetaxel) or Xtandi. Then the top competitors in the second-line setting will be Lynparza, Rubraca and Keytruda (pembrolizumab), he says.

Asked how the two PARP inhibitors compare with other therapies in the class, Tegenu points out that “Lynparza had higher objective response rates and better radiographic progression-free survival compared to enzalutamide and abiraterone. It also showed benefit compared to docetaxel. Men with specific mutations may benefit more with PARP inhibitors.”

“Rubraca after receiving taxane therapy showed benefit,” he continues. “It is currently being compared to abiraterone, enzalutamide or docetaxel in an ongoing clinical trial. It has accelerated approval contingent upon verification of success in this trial.”

Uncertainties Over Effectiveness and High Costs Surround DMD Therapies

June 10, 2020

Since 2016, the FDA has approved a handful of therapies to treat Duchenne muscular dystrophy (DMD). But some uncertainty exists over their effectiveness, in addition to concerns about their costs.

When DMD is suspected, a blood test that measures creatine kinase (CK) levels is performed. “CK is an enzyme found in abnormally high levels when muscle is damaged,” says Mesfin Tegenu, R.Ph., president of PerformRx, LLC. “The detection of an elevated CK level leads to molecular genetic testing to confirm a definitive diagnosis of DMD.”

By Angela Maas

Since 2016, the FDA has approved a handful of therapies to treat Duchenne muscular dystrophy (DMD). But some uncertainty exists over their effectiveness, in addition to concerns about their costs.

When DMD is suspected, a blood test that measures creatine kinase (CK) levels is performed. “CK is an enzyme found in abnormally high levels when muscle is damaged,” says Mesfin Tegenu, R.Ph., president of PerformRx, LLC. “The detection of an elevated CK level leads to molecular genetic testing to confirm a definitive diagnosis of DMD.”

In February 2017, the FDA approved then-manufacturer Marathon Pharmaceuticals LLC’s Emflaza (deflazacort). The company said it would be priced at $89,000, which sparked outrage since people have been buying a generic version from overseas since the 1990s for about $1,000 per year. After the backlash, Marathon ultimately sold the drug to PTC Therapeutics Inc., which launched it later that year with a $35,000 annual price tag. Since then, PTC has raised the price to more than Marathon’s original one.

In September 2016, the FDA gave accelerated approval to Sarepta Therapeutics, Inc.’s Exondys 51 (eteplirsen). The dystrophin gene has 79 exons, and about 80% of people with DMD have genotypes that are amenable to exon skipping. Exondys 51 targets those with a mutation of the DMD gene that is amenable to exon 51 skipping.

Sarepta also has a second exon-skipping therapy, Vyondys 53 (golodirsen), which treats DMD in people with a mutation amenable to exon 53 skipping. The FDA gave the drug accelerated approval in December, almost four months after the agency rejected the drug through a complete response letter.

Both drugs are weight-based with similar prices: about $300,000 per year but up to $1 million annually.

“It’s unclear how much a health plan may spend on someone with DMD; however, a recent study from the Muscular Dystrophy Association found that the annual cost for DMD for U.S. society as a whole is around $362-$488 million dollars,” says Tegenu. “The price of the newer DMD therapies (Exondys 51 and Vyondys 53) are both estimated to cost approximately $750,000 per year for the treatment of one patient.”

Pharma manufacturers continue to focus on the DMD space, and several products, including gene therapies, are in the pipeline.

COVID-19 Pandemic Drives Home Infusion Utilization

May 21, 2020

With numerous hospitals focused on the COVID-19 pandemic and many areas under stay-at-home mandates, home infusion is more important than ever. Changes within the industry already have been seen, and the current situation is likely to result in permanent shifts within the home infusion space.

“If you can do infusion at home, you need to do it there,” maintains Ashraf Shehata, KPMG national sector leader for Healthcare & Life Sciences. “This is about controlling infection risk in the near term, and many home infusion candidates are in a high-risk category. Longer term, there has been a shift toward delivering care in the most economical and clinically appropriate setting, largely driven by payers.”

By Angela Maas

With numerous hospitals focused on the COVID-19 pandemic and many areas under stay-at-home mandates, home infusion is more important than ever. Changes within the industry already have been seen, and the current situation is likely to result in permanent shifts within the home infusion space.

“If you can do infusion at home, you need to do it there,” maintains Ashraf Shehata, KPMG national sector leader for Healthcare & Life Sciences. “This is about controlling infection risk in the near term, and many home infusion candidates are in a high-risk category. Longer term, there has been a shift toward delivering care in the most economical and clinically appropriate setting, largely driven by payers.”

“We have seen an increase in some home infusion utilization of select therapies in certain markets where patient administration sites of care are shifting from the acute care or hospital outpatient setting to the home, related to the pandemic,” says Drew Walk, CEO of Soleo Health.

Some plans already have been shifting administration of certain therapies to patient homes and provider offices, which are more cost-effective settings than hospitals, points out Elan Rubinstein, Pharm.D., EB Rubinstein Associates.

“There could be more home infusion, with drugs that pose low risk of serious adverse events during or immediately after infusion or where a patient tolerated prior infusions of these drugs with no or minimal difficulty,” says Rubinstein.

Lisa Kennedy, Ph.D., chief economist and managing principal at Innopiphany LLC, points out that while CMS has changed some policies in support of home infusion, “not everyone is on board.” She notes that the Community Oncology Alliance “has raised safety concerns about home infusion centered on a lack of training of those in the community administering treatment at home versus trained oncology nurses.”

“Going forward there will be a lot of candidates for home infusion, and some customers/patients may like the convenience of getting care at home,” says Shehata. “There might be opportunities for alternative care models to be introduced here. The ability for nurses to teach patients how to self-administer the medicines is an important facet to this.”

As Step Therapy Becomes More Popular, Opinions Vary on Its Usefulness

February 10, 2020

Step therapy has long been a go-to utilization management strategy for payers, as it is often applied to specialty drugs. But as more and more costly medications come onto the market, the practice has become nearly ubiquitous, prompting some pushback from various stakeholders.

By Angela Maas

Step therapy has long been a go-to utilization management strategy for payers, as it is often applied to specialty drugs. But as more and more costly medications come onto the market, the practice has become nearly ubiquitous, prompting some pushback from various stakeholders.

“Step therapy can be a very good method of ensuring that patients always get the treatment that is clinically best for them,” states Lisa Kennedy, Ph.D., chief economist and managing principal at Innopiphany LLC. “In theory it should ensure that they consistently receive the safest, most effective and best tolerated treatment.”

Larry Kocot, the national leader of KPMG’s Center for Healthcare Regulatory Insight, tells AIS Health that “when used effectively, step therapy can help prevent the use of more costly, unnecessary medications, thereby helping to control overall prescription costs and ensuring that patients receive the most economical and effective treatment for them.”

A study by consulting group Visante Inc. that was commissioned by the Pharmaceutical Care Management Association (PCMA) and released in January 2019 found that step therapy can result in savings of more than 10% for targeted categories. PCMA is a PBM advocacy group.

However, notes Kocot, there is “some evidence that although step therapy often results in reduced prescription drug spending, outpatient services spending can increase.”

Step therapy, “like other prior-authorization requirements, complicates prescriber decision making and reduces prescriber and office efficiency,” says Elan Rubinstein, Pharm.D., principal at EB Rubinstein Associates. Kocot adds that while the clinical evidence used to establish step-therapy protocols “may be applicable to most patients, it is possible that certain individuals may not have typical responses or protocols.”

“The problem arises when step therapy is applied for cost reasons in the absence of clinical rationale and even worse when there is a financial rebate for drugs on a formulary, requiring patients to step through treatments not because of clinical reasons but because a payer or PBM receives a financial rebate for this (e.g., in commercial plans),” Kennedy says.

In addition, she says, “if a patient is subject to stepping through treatments, and this delays getting the correct treatment on time, this can have a monumental impact on outcomes and is a perfect example of where misapplied, step therapy can result in sicker patients who suffer more and are placed at greater risk of death.”

New Oncology Biosimilar Launches Could Prompt Preferencing

February 3, 2020

So far, biosimilar uptake has been relatively slow in the U.S. since the 2015 launch of Sandoz Inc.’s Zarxio (filgrastim-sndz), the first product to use the 351(k) approval pathway. But recent and pending launches have resulted in therapeutic classes with more than one biosimilar, which may be the push that payers need to begin preferring them over their reference products and, in turn, realizing savings in some costly therapeutic classes.

By Angela Maas

So far, biosimilar uptake has been relatively slow in the U.S. since the 2015 launch of Sandoz Inc.’s Zarxio (filgrastim-sndz), the first product to use the 351(k) approval pathway. But recent and pending launches have resulted in therapeutic classes with more than one biosimilar, which may be the push that payers need to begin preferring them over their reference products and, in turn, realizing savings in some costly therapeutic classes.

Although the FDA had approved 26 biosimilars as of the end of January, only half of them are available in the U.S., with many of the drugmakers tied up in patent litigation with reference drug manufacturers.

2019 saw the launch of the first oncology biosimilars when Amgen and Allergan plc launched Kanjinti (trastuzumab-anns), a Herceptin (trastuzumab) biosimilar, and Mvasi (bevacizumab-awwb), an Avastin (bevacizumab) biosimilar, on July 18. Both reference drugs are from Genentech USA, Inc., a Roche Group unit. Then, on Nov. 7, Teva Pharmaceuticals USA, Inc. and Celltrion launched Truxima (rituximab-abbs), with reference drug Rituxan (rituximab) from Genentech and Biogen.

The Dec. 2 launch of Mylan N.V. and Biocon Ltd.’s Ogivri (trastuzumab-dkst) brought a second biosimilar of Herceptin onto the U.S. market, with a third — Pfizer’s Trazimera (trastuzumab-qyyp) — expected Feb. 15. Also expected to launch in the first part of this year are Ontruzant (trastuzumab-dttb) from Samsung Bioepis Co., Ltd. and Herzuma (trastuzumab-pkrb) from Celltrion and Teva.

A second Avastin biosimilar came onto the U.S. market Dec. 31 when Pfizer launched Zirabev (bevacizumab-bvzr). Rituxan also had additional biosimilar competition on Jan. 23 when Pfizer’s Ruxience (rituximab-pvvr) launched.

Kanjinti is priced 15% less than Herceptin, and its average sales price (ASP) is 13% below the reference drug. Ogivri’s price is “at a competitive discount,” according to Mylan and Biocon. Mvasi is priced 15% less than Avastin, and its ASP is 12% less than that of the reference drug. Zirabev is priced 23% less than Avastin, and Ruxience is 24% less than Rituxan.

“As more health plans set biosimilars on a preferred status, adoption and utilization should increase,” says Martin Burruano, R.Ph., vice president, pharmacy services at Independent Health. “As more become available, there will be opportunity to plan formulary selection to drive costs down. Projections are modest at 12%-15% cost savings initially but will potentially reach 70% cost savings in five years.”