Investors continue to keep a close eye on the progress of companies involved in developing medicines targeting the central nervous system and, in the main, their reaction has been generally positive. The BioWorld Neurological Diseases index, a price-weighted index of public biopharmaceutical companies that are focused on developing therapies to treat neurological diseases, closed the year up over 16% and after, a dip in January, is now tracking up more than 12% by market close on Friday, Feb. 21, well ahead of the general markets for the same period. (See BioWorld Neurological Diseases index, below.)

Major mover

Leading gainer this month is Biogen Inc., of Cambridge, Mass., with its share value (NASDAQ:BIIB) up more than 25%, up 13.5% for the year. Its recent uptick canceled out the almost 10% decline last month, despite reporting total revenues of $14.37 billion for 2019, up 7% over the prior year. Full-year sales of multiple sclerosis drugs, including $688 million in royalties on sales of Ocrevus (ocrelizumab), totaled $9.21 billion, up 2% over 2018. Sales of spinal muscular atrophy drug Spinraza (nusinersen) jumped 22% over the prior year to $2.09 billion.

The company also reported it had signed an agreement to acquire PF-05251749, a CNS-penetrant small-molecule inhibitor of casein kinase 1 (CK1), for the potential treatment of patients with behavioral and neurological symptoms across various psychiatric and neurological diseases, from Pfizer Inc. The purchase price includes an up-front payment of $75 million with up to $635 million in potential additional development and commercialization milestone payments, as well as tiered royalties in the high single digits to subteens. Biogen expects the transaction to close in the first quarter.

Going forward, it plans to develop the phase I asset for the treatment of sundowning in Alzheimer’s disease (AD) and irregular sleep wake rhythm disorder (ISWRD) in Parkinson’s disease (PD).

Commenting on the transaction, SVB Leerink’s Geoffrey Porges said, “The commercialization of PF-05251749 should be quite synergistic with the commercialization of aducanumab and other disease-modifying medicines for either AD or PD, should they be successful.”

Camp4 Therapeutics Inc. also established a collaboration with Biogen that is designed to leverage Camp4’s gene circuitry platform with the aim of identifying how to dial up or down the expression of disease-associated genes within microglial cells – the primary immune cells of the central nervous system, which are implicated in many serious neurological and neurodegenerative diseases. Camp4 will receive a $15 million up-front payment and Biogen will reimburse it for research activities. In return, Biogen will have the option to select resulting targets to advance to discovery, development and commercialization. Camp4 will be eligible to receive development and milestone payments of up to $96 million, plus future royalties, for each of the initial selected targets and up to $173 million, plus future royalties, for each additional target.

Investors were also impressed with the drug pipeline progress of Radnor, Pa.-based Marinus Pharmaceuticals Inc., driving its shares up (NASDAQ:MRNS) 40%. The company is developing an oral and intravenous formulation of ganaxolone to treat adults and children suffering from acute and chronic rare neuropsychiatric conditions where there is a mechanistic rationale for ganaxolone to provide a benefit. It has entered the final stages of recruitment in the Marigold study, its pivotal phase III trial evaluating oral ganaxolone in children and young adults with CDKL5 deficiency disorder (CDD), a rare refractory form of pediatric epilepsy with no currently approved treatments. Approximately 100 patients between the ages of 2 and 21 with a confirmed disease-related CDKL5 gene variant will be enrolled, with top-line data expected in the third quarter of 2020.

Slow recovery

Shares of Cambridge, Mass.-based Wave Life Sciences Ltd. (NASDAQ:WVE) were under pressure late last year following its decision to discontinue development of suvodirsen for patients with Duchenne muscular dystrophy who have mutations amenable to exon 51 skipping, based on its interim analysis of a phase I open-label extension study. The results showed no change from baseline in dystrophin expression, as measured by western blot, with either the 3.5-mg/kg or 5-mg/kg doses of suvodirsen.

Shares lost an additional 49.5% of their value as investors learned of top-line data from the ongoing phase Ib/IIa Precision HD2 trial testing WVE-120102 in Huntington’s disease (HD).

Wave’s candidate, designed to be the first allele-selective approach to treat HD, seemed to do well. In an analysis comparing all patients treated with multiple intrathecal doses of WVE-120102 to placebo, a statistically significant reduction of 12.4% (p<0.05) in mutant huntingtin (mHTT) protein was observed in cerebrospinal fluid. Dose response across treatment groups (2 mg, 4 mg, 8 mg or 16 mg) suggested a statistically significant response in mHTT reduction at the highest doses tested (p=0.03) with WVE-120102 generally safe and well-tolerated across all cohorts, the company said.

With a 32-mg cohort study in the works, the company’s share value did stage a recovery, rising 25% this month.