Eli Lilly Wins with Single-Dose Vials for Obesity Drug

Eli Lilly announced in late August that it slashed more than 50% off the list price of all incretin (GLP-1) medicines for obesity by offering Zepbound (tirzepatide) 2.5 mg and 5 mg in single-dose vials.

For self-payers without health insurance, a four-week supply of the 2.5 mg Zepbound in the single-dose vial is $399, or $99.75 per vial. A four-week supply of the 5 mg dose is $549, or $137.25 a vial.

A win for now.

Lilly’s new self-pay pharmacy, LillyDirect, allows patients with a valid, on-label prescription to purchase the vials, effectively competing with potentially unsafe but more affordable “counterfeit, fake, unsafe or untested knockoffs of Lilly's medications,” according to the release. It also removes traditional pharmacies and pharmacy benefit managers from the sales equation.

Reuters reported that while Lilly and competitor Novo Nordisk (maker of Wegovy) struggled to meet high demand for obesity medications, Lilly increased manufacturing, raising its sales forecast by $3 billion. Novo’s Wegovy remains on the FDA’s shortage list.

“Citi analyst Daniel Grosslight said the move would alleviate the supply bottleneck around auto-injector pens,” according to Reuters.

Zepbound is also available in 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per 0.5 ml doses in a single-dose pen, or autoinjector. The recommended maintenance dosages are 5 mg, 10 mg, or 15 mg injected subcutaneously once weekly, according to Lilly’s release.

Related:Eli Lilly Opens $2B Pharmaceutical Facility

Not always the best option.

The FDA defines a single-dose container as a container of a sterile medication for parenteral administration (injection or infusion) that is not required to meet antimicrobial effectiveness testing requirements. It’s designed for use with a single patient as a single injection/infusion.

“When space permits, a single-dose container is labeled as such and should include on the label appropriate discard statements. Examples of single-dose containers are vials, ampules, and prefilled syringes,” according to FDA.

There are pros and cons to using different self-injection methods. Authors of a narrative review in Advances in Therapy studied outcomes of studies looking at biologic use, self-administered by patients using vials and syringes, prefilled syringes, and spring-driven prefilled pens or auto-injectors. They concluded: “Prefilled syringes and pens have been available for some years to assist patients with self-injection, and both are extremely useful and valued options for patients who self-inject and offer various advantages over vials and syringes. However, prefilled pens and syringes are not suitable for everyone, and some patient needs remain unmet, meaning there is room for further improvement: notably in reducing injection-site pain, suboptimal adherence, and the large single-use plastics burden associated with prefilled pens.”

The National Academies of Sciences, Engineering, and Medicine’s publication “Single-Dose Vials of Weight-Based Drugs” points to the needs for regulatory guidance governing vial sharing and incentives that encourage efficient use of infused or injectable drugs in single-dose vials, since pharma and providers receive payment for the amount of drug in a single-dose vial, including that which is discarded.

Are single-dose vials about to get really popular?

Rich Hollander, who retired from Pfizer after 32 years in various leadership roles in packaging and sterile injectable technology and now leverages his expertise to help companies with operational and technical challenges they face, is hesitant to predict that single-dose vials will become a pharmaceutical industry trend.

He says the decision for a company to commercialize a single-dose vial versus a pre-filled syringe, multi-dose vial, or multi-dose auto-injector is complicated and always well thought out.

Hollander points to commercial aspects, including therapeutic area, price, supply, cost, and what the competition is doing, as well as considerations like who is administering the drug, whether it is done in a clinical setting or at home, and how frequently. Then, there are the regulatory considerations — is it approved in the filling and, if not, how much effort will it take to introduce single-dose vials?

Lastly, there’s capacity.

“Single-dose vials by definition eat up a fair bit of capacity on filling lines,” Hollander says.

Companies often start with a single-dose vial in early-stage clinical trials. Later stage clinical stage trials will also consider prefilled syringes for a single dose or auto-injectors for multiple dose applications, according to Hollander.

“Multi-dose vials may be a follow-on if they make sense and might also be in the initial filing," he explains. "But if there are commercial pressures — usage/compliance needs, competitors — an auto-injector will likely be the ‘go to’ design for markets that can afford them. … vials and potentially prefilled syringes would be leveraged for the rest of the world."

Companies should consider introducing vials if there is a capacity issue with injectors that is impacting patient access.

“Clearly compounding pharmacies have noted that and have been working to fill the void,” Hollander adds. “Compounding pharmacies that handle sterile injectables are in a high-risk business. While they serve an important need to enable some incremental supply, they are not required to fulfill the same FDA manufacturing requirements the drug license holder meets when producing Sterile Injectable drugs in a cGMP facility.”

Hollander doesn’t view patient safety or patient preference as big concerns because of the high demand for GLP-1 drugs. Many patients, including older insulin users, are familiar with withdrawing product from a vial and injecting themselves. 

“These products work, and while the convenience of an auto-injector is of course nice, most people, if given a choice of drug in a vial or no drug at all, will pick the vial,” Hollander says.