Welcome to your weekly digest of approaching regulatory and clinical readouts. Agile Therapeutics’ weekly contraceptive patch Twirla is set to get another crack at US approval, with an FDA decision due by December 26; however, it might have a hard time as phase III results were far from convincing.
And interim data are due by the end of the year for Allergan’s brimonidine intravitreal implant, which is in a phase II study in the eye disorder geographic atrophy. This under-the-radar asset is a high-risk/high-reward play for Allergan, as nothing has worked in the disease so far.
Give us a Twirla
It is judgement time for Twirla. Again. After an FDA knockback in 2013 Agile Therapeutics has spent the past four years assembling additional clinical data for its lead project.
However, the latest phase III trial, Secure, reported lower efficacy than has historically been seen with older contraceptives, so approval is far from a given. Agile blamed a high proportion of obese women in the trial – this population has a higher risk of pregnancy while on contraceptives.
The company obviously feels hopeful this time around; in August it raised $18.5m to push its cash pile up to $43.8m, ostensibly to fund Twirla’s launch. Investors also appear to share this optimism, with shares in the group having risen by 49% in the past six months.
But, even if it is successful on the regulatory front, commercialisation might be harder four years on. Twirla will be up against generic contraceptive patches based on Janssen’s Ortho Evra.
However, Ortho Evra was pulled from the market in 2014 over safety concerns. Agile hopes that its low-dose formulation of asynthetic oestrogen and progestin will avoid some of the vein thrombosis issues that led Janssen to discontinue its product.
Twirla also offers convenience for customers who might not want the hassle of remembering to take daily oral contraceptives but desire the flexibility of a shorter-acting from of pregnancy control versus a depot injection.
But making headway in a largely generic market, with many entrenched players, will require Twirla’s reps to work extra hard for the $330m of sales the treatment is forecast to generate in 2022.
This all assumes a regulatory green light. If history repeats itself, investors who have patiently waited for Twirla’s second chance are unlikely to hang around to see if Agile’s other contraceptive patches work out.
Allergan eyes up new indication
Brimonidine, an alpha-2 adrenergic receptor agonist, is the active ingredient in Allergan’s Combigan and Alphagan eye drops, which are marketed for reducing intraocular pressure in patients with glaucoma or ocular hypertension.
Animal models have suggested that the compound might also be neuroprotective, a mechanism that could be useful in geographic atrophy (GA). In this advanced form of dry age-related macular degeneration the death of retinal pigment epithelial cells leads to irreversible vision loss.
Allergan has developed a biodegradable polymer implant formulation, brimonidine-DDS, and it is this that it is testing in GA in the phase II Beacon trial. The implant, injected every three months, is being compared versus sham treatment, with a primary endpoint of change from baseline in atrophic lesion area in the study eye at 24 months.
The 310-patient trial is due to end in September 2018, but Allergan plans to conduct an interim analysis before the end of the year and, if the results are positive, to begin a phase III trial.
Hopes for GA projects are not high after Roche’s lampalizumab flopped in two pivotal studies earlier this year. The failure also hit sentiment for Ophthotech’s similarly acting project Zimura, which is in a phase II/III trial in GA.
Unlike brimonidine, lampa and Zimura both target the complement pathway. Still, even the sellside calls Allergan’s attempt in GA a long shot – albeit one that could see it reap huge rewards if it comes off.
Bernstein says if the implant gets approved it could bring in $2bn a year, based on 20% US market penetration at a price of $10,000 per year. First, though, brimonidine has to succeed where others have failed.